Head and Neck

Prospective evaluation of XRCC‐1 Arg194Trp polymorphism as bio‐predictor for clinical outcome in locally advanced laryngeal cancer undergoing cisplatin‐based chemoradiation

30-01-2020 – Vijay Raturi, Hidehiro Hojo, M. L. B. Bhatt, Mohammad Suhel, Chen‐Ta Wu, Yanping Bei, Masaki Nakamura, Masayuki Okumura, Haiqin Zhang, Devendra Parmar, Avinash Badajena, Rahul Singh, Saurabh Kumar, Tridev Katiyar, Jalaj Gaur

Abstract
Background
To determine X‐ray repair cross‐complementing 1 gene (XRCC‐1) Arg194Trp polymorphism as bio‐predictor for clinical outcome in advanced laryngeal squamous cell carcinoma undergoing cisplatin‐based chemoradiation (CRT).
Methods
A total of 150 patients were enrolled in this prospective study. XRCC‐1 Arg194Trp genotyping categorized patients as wild (C/C) and polymorphic (C/T or T/T). The primary endpoint was to assess acute radiation‐induced toxicity (ARIT).
Results
A significant correlation of skin (P‐ .04) and oral mucosal ARIT (P‐ .01) was noticed in the XRCC‐1 polymorphic variant. A higher treatment response was noted in the polymorphic variant, and it shows a trend toward significance (P‐ .08). With 33 months of median follow‐up, 2‐year progression‐free survival (PFS) and overall survival (OS) of wild vs polymorphic variant were 34.6% vs 46.9% (P‐ .066) and 50.6% vs 62.2% (P‐ .12).
Conclusion
XRCC‐1 polymorphic variants have significantly higher grade of >2 ARIT and may have improved trend for treatment response and PFS.

Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin

27-01-2020 – Paul L. Swiecicki, Pin Li, Emily Bellile, Chaz Stucken, Kelly Malloy, Andrew Shuman, Matthew E. Spector, Steven Chinn, Keith Casper, Scott McLean, Jeffery Moyer, Douglas Chepeha, Gregory T Wolf, Mark Prince, Carol Bradford, Mukesh Nyati, Avraham Eisbruch, Francis P Worden, Shruti Jolly, Michelle Mierzwa

Journal Article

Abstract
Background
Alternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for de‐escalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximab‐radiotherapy.
Methods
We conducted paired phase II trials evaluating cetuximab‐radiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean follow‐up was 48 months.
Results
Forty‐two patients were enrolled in cohort A with a 2‐year disease free survival (DFS) of 81%. Twenty‐one patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2‐year DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition.
Conclusion
Among cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinum‐based regimens suggesting that cetuximab is not a benign treatment.

Trends in head and neck fellowship graduates in the United States from 1997 to 2017

27-01-2020 – Yufan Lin, Dhruv Patel, Tam Ramsey, Neil Gildener‐Leapman

Journal Article

Abstract
Background
We investigated whether the supply of head and neck fellowship graduates matches head and neck cancer trends.
Methods
Graduates between 1997 and 2017 from the American Head and Neck Society (AHNS) and United States Otolaryngology fellowship program webpages were identified. Trends in graduates were compared with head and neck cancer incidence obtained from the Center of Disease Control.
Results
Of 538 fellows, 428 were from the United States. Of fellows practicing in the United States, 24.14% were female. Most practice locations were urban (98.44%). AHNS fellowship positions from 1997 to 2017 increased by nearly 1.82 per year (P < .00001). Graduates in academic positions increased by 1.03 per year (P < .00001). Concomitantly, the age‐adjusted incidence rate of oral, oropharyngeal, and laryngeal cancers decreased (P = .0115).
Conclusion
There is important geographic variability in the practice locations of Head and Neck Oncologic Surgeons in the United States and our data may be helpful in matching clinical supply and demand.

MicroRNA‐based risk scoring system to identify early‐stage oral squamous cell carcinoma patients at high‐risk for cancer‐specific mortality

25-01-2020 – Angela J. Yoon, Shuang Wang, David I. Kutler, Richard D. Carvajal, Elizabeth Philipone, Tian Wang, Scott M. Peters, Dominic LaRoche, Brenda Y. Hernandez, Bradley D. McDowell, Claire R. Stewart, Fatemeh Momen‐Heravi, Regina M. Santella

Journal Article

Abstract
Background
For early‐stage oral squamous cell carcinoma (OSCC), there is no existing risk‐stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer‐specific mortality.
Methods
A total of 568 early‐stage OSCC patients who had surgery only and also with available 5‐year clinical outcomes data were identified. Signature micro
RNAs (mi
RNAs) were discovered using deep sequencing analysis and validated by q
RT‐PCR. The final 5‐plex prognostic marker panel was utilized to generate a cancer‐specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts.
Results
The risk score from the 5‐plex marker panel consisting of mi
RNAs‐127‐3p, 4736, 655‐3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low‐risk group, the high‐risk group had 23‐fold increased mortality risk (hazard ratio 23, 95% confidence interval 13‐42), with a median time‐to‐recurrence of 6 months and time‐to‐death of 11 months (vs >60 months for each among low‐risk patient; p < .001).
Conclusion
The mi
RNA‐based 5‐plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early‐stage OSCC.

Fractionation scheme and treatment planning method for early glottic cancer in the United States: Economic impact of different medical decisions

24-01-2020 – Assaf Moore, Robert B. Den, Aaron Popovtzer, Hadar Goldvaser, Noa Gordon, Daniel A. Goldstein

Journal Article

Abstract
Background
Early glottic cancers are often treated with radiotherapy (RT). We assessed the economic impact of fractionation scheme and planning method for payers in the United States.
Methods
A population‐based analysis of the total cost of RT for early glottic cancers in the United States was performed annually. The target population was calculated using the Surveillance, Epidemiology, and End Results database. RT costs were based on 2019 pricing by Medicare.
Results
We estimate that 3794 patients with early glottic cancers are treated with RT annually. The cost of RT per patient ranges between US $13 964 and $26 599 by fractionation and planning method. Hypofractionation reduces costs by 9% to 14%, while Intensity‐modulated radiotherapy (IMRT) increases costs by 65% to 72%. IMRT‐based standard fractionation leads to an excess cost of $47 937 076 compared with 3D‐based hypofractionation.
Conclusions3D‐based hypofractionated RT is the current standard of care. It would be reasonable for public and private payers to consider evidence‐based policies for radiation reimbursement.

Facial functional outcomes analysis after reconstruction by vascularized thoracodorsal nerve free flap following radical parotidectomy with facial nerve sacrifice

24-01-2020 – Vincent Bedarida, Quentin Qassemyar, Stéphane Temam, François Janot, Frédéric Kolb

Journal Article

Abstract
Background
Parotid spread tumor may occasion wide defect with facial nerve sacrifice. We report our one time reconstruction experience of this defect using a thoracodorsal artery perforator and nerve flap (TAPN).
Methods
Eight patients underwent a radical parotidectomy with facial nerve sacrifice between February 2010 and June 2016. A single time reconstruction was performed using a thoracodorsal artery perforator and nerve flap, with skin or fat paddle. The thoracodorsal nerve vascularized was harvested and used to reconstruct the facial nerve from the trunk to four until six distal branches. Patients underwent physiotherapy for 3 months at least. Facial outcomes were assessed using House‐Brackmann scale and e
FACE application.
Outcomes
Mean follow‐up was 30 months. No complication occurred on donor site. All patients recovered a complete soft eye closure. No Frey syndrome occurred.
Conclusion
TAPN is adapted to wide and complex parotid defects.

Techniques of endoscopic nasopharyngectomy for localized stage I nasopharyngeal carcinoma

24-01-2020 – You‐Ping Liu, Yu‐Long Xie, Xiong Zou, Rui You, Qi Yang, Ming‐Yuan Chen

Journal Article

Abstract
Background
Endoscopic surgery was widely applied as radical treatment for early cancer. We aimed to demonstrate the details of endoscopic nasopharyngectomy (ENPG) for nasopharyngeal carcinoma (NPC).
Methods
Before operation, we first defined the gross tumor volume (GTV) and surgical tumor volume (STV) for resection. STV was defined as gross tumor volume plus an additional 0.5‐1.0 cm peripheral mucosa margin and a 2‐3 mm basal margin on the surface skull base. The surgeon was required to follow this planned STV to remove the tumor.
Results
En bloc resection was achieved in the endoscopic operation, and multiple margin biopsies were proved pathologically negative. Comparison between preoperative and postoperative magnetic resonance imaging revealed that actual STV (a
STV) had contained the STV completely. Mostly, no death, recurrence, or distant metastasis was observed in this case during the 3‐year follow‐up.
Conclusions
Techniques of ENPG for treating newly diagnosed localized stage I NPC patients were feasible.

Prognostic value of post‐ablation 131I scintigraphy in children with thyroid cancer

24-01-2020 – Xinyue Zhang, Lina Liu, Yu Chen, Rui Huang, Bin Liu

Journal Article

Abstract
Background
To evaluate the prognostic value of post‐ablation whole‐body scintigraphy (PAS) in children with thyroid cancer following 131I therapy.
Methods
A retrospective analysis of children with thyroid cancer who underwent remnant ablation was performed. PAS results were correlated with clinical and histopathologic characteristics of the primary tumor and compared with the follow‐up data.
Results
One hundred and sixty‐eight children were eligible for the analysis. The median age was 17 years, and the majority were female (81.5%). In multivariate analysis, N1b classification and 131I ablative dose were associated with PAS positivity. After a median follow‐up of 49 months, 89 (71.8%) of 124 children with normal PAS achieved complete remission. Fifteen of 44 (34.1%) children with positive PAS had complete remission. Kaplan‐Meier analysis showed that positive PAS was negatively associated with cumulative complete remission rates (P < .001).
Conclusions
PAS could provide prognostic information in children with thyroid cancer undergoing 131I therapy.

Central pathology review of salivary gland adenoid cystic carcinoma

23-01-2020 – Kaori Ueda, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Makoto Urano, Hidetaka Yamamoto, Masato Nakaguro, Ken‐ichi Taguchi, Ayako Masaki, Hideaki Hirai, Daisuke Kawakita, Kiyoaki Tsukahara, Naohito Hato, Toru Nagao, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Satoshi Kano, Tetsuro Onitsuka, Kenji Okami, Ken‐ichi Nibu, Yuichiro Tada, Ryo Kawata, Hiroshi Inagaki

Journal Article

Abstract
Background
To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (Ad
CC).
Methods
Surgically resected salivary gland tumors diagnosed as Ad
CC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re‐evaluation.
Results
After the review, the Ad
CC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants.
Conclusions
A significant proportion of Ad
CC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating Ad
CC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.

Neck Dissection Brendan C. Stack, Jr., Mauricio A. Moreno Thieme Publishers, New York, NY, 2019, 301 pp, $129.99

22-01-2020 – Garren M. I. Low

Clinical and sociodemographic factors associated with oral health‐related quality of life in survivors of head and neck cancer

21-01-2020 – Eloisa B. Soldera, Gabriela B. Ortigara, Laura I. L. Bonzanini, Riéli E. Schulz, Cristiane C. Danesi, Raquel P. Antoniazzi, Kívia Linhares Ferrazzo

Journal Article

Abstract
Background
Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health‐related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis.
Methods
This cross‐sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP‐14) and the data were analyzed using robust variance poisson regression models.
Results
The mean total OHIP‐14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP‐14 total scores (CI:1.11‐2.18) and patients with advanced stage tumors had 31% higher mean OHIP‐14 total scores (CI:1.03‐1.66) in multivariate analyses.
Conclusion
OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.

The effect of jaw exercises on anxiety and depression in patients with head and neck cancer receiving radiotherapy: Prospective 2‐year follow‐up study

16-01-2020 – Susan Aghajanzadeh, Therese Karlsson, Lisa Tuomi, Caterina Finizia

Journal Article

Abstract
Background
This nonrandomized matched study investigates jaw exercise effect on anxiety/depressive symptoms in head and neck cancer patients with trismus during 2 years postradiotherapy.
Methods
Fifty patients with trismus postradiotherapy were included in a 10‐week jaw‐training intervention. A matched control group was included (N = 50). Maximum interincisal opening (MIO) ≤ 35 mm was used as the trismus criterion. Patients were assessed using MIO and Hospital Anxiety Depression Scale preintervention, postintervention, and at 2‐year follow‐up.
Results
A significant difference was found in depressive symptoms between the intervention group and control group (4% vs 33%) at 2‐year follow‐up, with more control group patients reporting possible depression. In the intervention group, significantly fewer patients had possible/probable depressive symptoms at follow‐up (4%) compared to preintervention (34%). No change was seen within the control group.
Conclusion
Structured jaw exercise in patients with postradiation trismus had positive effects on MIO and depressive symptoms but does not seem to have any significant effects on anxiety symptoms.

Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma

16-01-2020 – Felipe Galiza Barbosa, Oliver Riesterer, Stephanie Tanadini‐Lang, Sonja Stieb, Gabriela Studer, Martin Pruschy, Gerhard F. Huber, Martin W. Huellner, Paul Stolzmann, Patrick Veit‐Haibach

Journal Article

Abstract
Background
To determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy.
Methods
A total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS).
Results
Thirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P > .05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P > .05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P < .01).
Conclusions
Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker.
Trial registration
Clinical Trials.gov identifier: NCT01435252.

Closure of radial forearm free flap donor site: A comparative study between keystone flap and skin graft

16-01-2020 – Pauline Potet, Guillaune De Bonnecaze, Emilien Chabrillac, Agnès Dupret‐Bories, Sébastien Vergez, Benoit Chaput

Journal Article

Abstract
Background
The aim was to investigate the feasibility of radial forearm free flap (RFFF) donor site closure by keystone flap (KF) and compare its outcomes to those of skin graft (SG) closure.
Methods
One hundred and one patients who underwent RFFF for head and neck reconstruction were included (35 KF closure and 65 SG closure). Duration of wound healing and donor site complications was collected. After a minimal follow‐up of 1 year, patients were questioned about functional and esthetic impairment.
Results
Coverage of donor site by KF was successful in all cases. The duration of wound healing was longer after SG than after KF (32 days vs 18 days, P < .001). Healing complications, esthetic and functional results were not statistically different.
Conclusion
Forearm donor site closure by KF is a feasible alternative to the traditional SG. Its main advantages are the reduced wound healing time and the avoidance of a second donor site.

Prospective evaluation of oral premalignant lesions using a multimodal imaging system: a pilot study

16-01-2020 – Eric C. Yang, Imran S. Vohra, Hawraa Badaoui, Richard A. Schwarz, Katelin D. Cherry, Justin Jacob, Jessica Rodriguez, Michelle D. Williams, Nadarajah Vigneswaran, Ann M. Gillenwater, Rebecca R. Richards‐Kortum

Journal Article

Abstract
Background
Multimodal optical imaging, incorporating reflectance and fluorescence modalities, is a promising tool to detect oral premalignant lesions in real‐time.
Methods
Images were acquired from 171 sites in 66 patient visits for clinical evaluation of oral lesions. An automated algorithm was used to classify lesions as high‐ or low‐risk for neoplasia. Biopsies were acquired at clinically indicated sites and those classified as high‐risk by imaging, at the surgeons discretion.
Results
Twenty sites were biopsied based on clinical examination or imaging. Of these, 12 were indicated clinically and by imaging; 58% were moderate dysplasia or worse. Four biopsies were indicated by imaging evaluation only; 75% were moderate dysplasia or worse. Finally, four biopsies were indicated by clinical evaluation only; 75% were moderate dysplasia or worse.
Conclusion
Multimodal imaging identified more cases of high‐grade dysplasia than clinical evaluation, and can improve detection of high grade precancer in patients with oral lesions.

Clinical characteristics and prognostic factors of malignant tumors involving pterygopalatine fossa

16-01-2020 – Hyun‐Jae Woo, Peter H. Hwang, Michael J. Kaplan, Garret Choby

Journal Article

Abstract
Background
To identify the clinical characteristics and prognostic factors of malignancies involving the pterygopalatine fossa (PPF).
Methods
Fifty‐seven patients who underwent curative surgery for malignant tumor involving PPF were reviewed.
Results
The rates for three‐year local control (LC), five‐year disease‐free survival (DFS) and five‐year overall survival (OS) were 55.4%, 34.5%, and 52.7%, respectively. Perineural invasion (PNI) of the maxillary nerve with facial numbness (symptomatic V2 PNI) (P = .04) and cranial involvement (P = .03) were predictors for poor OS. Symptomatic V2 PNI was also a significant predictor for poor LC (P = .05) and DFS (P = .03). Within the subgroup analysis of patients with pathologically confirmed V2 PNI, asymptomatic V2 PNI patients had significantly better LC (71.2% vs 31.8%, P = .05) and DFS (43.8% vs 17.3%, P = .05) compared to symptomatic patients.
Conclusion
Malignant tumors involving the PPF have diverse pathologies and a poor prognosis. Symptomatic V2 PNI may be an independent poor prognostic factor.

Impact of active smoking on outcomes in HPV+ oropharyngeal cancer

16-01-2020 – Roy Xiao, Yvonne Pham, Matthew C. Ward, Narcissa Houston, Chandana A. Reddy, Nikhil P. Joshi, John F. Greskovich, Neil M. Woody, Deborah J. Chute, Eric D. Lamarre, Brandon L. Prendes, Robert R. Lorenz, Joseph Scharpf, Brian B. Burkey, Jessica L. Geiger, David J. Adelstein, Shlomo A. Koyfman

Journal Article

Abstract
Background
The role of smoking among patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is unclear.
Methods
A retrospective cohort study of patients with HPV(+) OPSCC from 2001 to 2015 at a tertiary‐care institution was conducted. The primary outcome was overall survival (OS).
Results
Among 484 included patients, 94 (19.4%) were active smokers, 226 (46.7%) were former smokers, and 164 (33.9%) never smoked. Among active smokers, 82 patients (87.2%) had a ≥10 pack‐year and 69 (73.4%) had a ≥20 pack‐year smoking history. After adjusting for covariates, active smoking was a significant predictor of inferior OS (HR 2.28, P < .001) and PFS (HR 2.26, P < .001). When including pack‐years as the covariate, ≥20 pack‐years predicted a decreased effect‐size for inferior OS and PFS.
Conclusions
For patients with HPV(+) OPSCC, active smoking at diagnosis is the most powerful covariate capturing smoking history to predict OS and PFS.

Management of unilateral head and neck carcinoma of unknown primary: Retrospective analysis of the impact of postoperative radiotherapy target volumes

16-01-2020 – Fabien Podeur, Pascal Pommier, Carole Crozes, Elodie Monchet, Jean Ton Van, Pierre‐Eric Roux, Marc Poupart, Philippe Zrounba, Morbize Julieron, Sophie Deneuve

Journal Article

Abstract
Background
We compared the outcome of postoperative unilateral cervical nodes radiotherapy (UL‐RT) vs bilateral cervical nodes plus total mucosal irradiation (COMP‐RT) in the management of head and neck carcinoma of unknown primary (HNCUP).
Methods
HNCUP, defined by the absence of primary despite a PET‐CT combined with a panendoscopy, were treated with curative intent by initial ipsilateral neck dissection. Sixty‐nine patients with unilateral HNCUP were included: 23 received UL‐RT while 46 received COMP‐RT. Carcinologic outcomes and long‐term quality of life (QOL) according to the QOL Questionnaire for Head and Neck 35 were assessed.
Results
Within 6.3 years of median follow‐up, there was no significant difference in primary tumor emergence rate (P = .68), cervical node recurrence rate (P = .34), or overall survival (P = .33) between UL‐RT and COMP‐RT groups. A trend toward QOL improvement was observed in the UL‐RT group.
Conclusion
UL‐RT seems to provide similar outcomes as COMP‐RT in unilateral HNCUP management.

Degree of technical difficulty of thyroidectomy for autoimmune thyroid disease

16-01-2020 – Robert Saadi, Alyssa Brandt, Yesul Kim, Elizabeth Cottrill, Brian Saunders, Eric Schaefer, David Goldenberg

Journal Article

Abstract
Background
Our goal was to elucidate the differences in degree of technical difficulty of thyroidectomy in patients with autoimmune thyroid diseases.
Methods
Charts of adult patients who had undergone thyroidectomy were reviewed. Patients with Hashimotos Thyroiditis (HT) or Graves Disease (GD) were individually compared to a control group of patients with early stage malignancy or goiter.
Results
The HT (n = 65) group was significantly more likely to have friable (P = .001) and fibrotic (P < .001) thyroids, longer operative times (P = .02), and a 22‐modifier (P = .005). The GD (n = 169) group was significantly more likely to have friable (P < .001), vascular (P < .001), fibrotic (P = .038), and heavy (P = .002) thyroids, longer operative times (P = .03), increased length of stay (P = .01) and a 22‐modifier (P = .01).
Conclusion
Our experience at an institution with a high‐volume thyroid practice demonstrates that patients with autoimmune thyroid disease have consistent qualitative changes of the thyroid and significantly increased operative times and surgical difficulty.

Assessment of shoulder function following scapular free flap

16-01-2020 – Krupal B. Patel, Tsu‐Hui (Hubert) Low, Allison Partridge, Anthony C. Nichols, S. Danielle MacNeil, John Yoo, Kevin Fung

Journal Article

Abstract
Background
The scapular system free flap has been increasing in popularity to reconstruct short segment mandibular bony defects. It is important to assess donor site morbidities systematically.
Methods
Prospective cohort study using objective measures of range of motion (ROM) and shoulder strength were measured. Subjective disability was evaluated with validated questionnaires—Neck Disability Impairment Index and Shoulder Pain and Disability Index.
Results
Twenty‐six patients were recruited—19 with scapular tip and 7 with lateral border scapular free flap. Decreased ROM on the operated side was noted for shoulder abduction, shoulder flexion, and external rotation. No significant difference was noted for shoulder extension. Strength was reduced for shoulder flexion, shoulder abduction, and external rotation. Subjective measurements did not indicate significant shoulder function disruption.
Conclusion
Patients with scapular free flap reconstruction did not experience significant shoulder morbidity. Measures of shoulder ROM and power were objectively affected; however, subjective measures of shoulder disability were not significantly affected.

Minimally invasive surgery for laryngopharyngeal cancer: Multicenter feasibility study of a combination strategy involving transoral surgery and real‐time indocyanine green fluorescence‐navigated sentinel node navigation surgery

16-01-2020 – Koji Araki, Masayuki Tomifuji, Akihiro Shiotani, Shigeru Hirano, Junkichi Yokoyama, Kiyoaki Tsukahara, Akihiro Homma, Seichi Yoshimoto, Yasuhisa Hasegawa

Journal Article

Abstract
Background
Sentinel node navigation surgery using indocyanine green (ICG‐SNNS) can be performed in the operation room. The combination of minimally invasive transoral surgery (TOS) with ICG‐SNNS can provide functional preservation options for both primary lesions and lymph node (LN) metastasis. This multicenter feasibility study of this strategy was conducted in Japan.
Methods
Patients with clinical T1 or T2, N0 oropharyngeal, hypopharyngeal, or supraglottic cancer were enrolled. The identification rate of sentinel nodes, delayed cervical LN metastasis in 2 years, and survival rate were assessed.
Results
Twenty‐two patients (10 oropharynx, 8 hypopharynx, 4 supraglottic cancer) were enrolled. The identification rate was 100%. One case had delayed nodal metastasis. The accuracy was 95.5%, sensitivity was 75%, and specificity was 100%. The 5‐year disease‐specific survival was 100%, overall survival was 72.3%, and disease‐free survival was 60.5%.
Conclusions
The combination of TOS with ICG‐SNNS is feasible as a minimally invasive strategy and has favorable oncological outcomes.

Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical No early oral tongue carcinoma

16-01-2020 – Yukiko Hori, Akira Kubota, Tomoyuki Yokose, Madoka Furukawa, Takeshi Matsushita, Nobuhiko Oridate

Journal Article

Abstract
Background
This study evaluated the combination of tumor budding and depth (BD model) and worst pattern of invasion (WPOI) as histopathological prognostic factors in clinical N0 early oral tongue carcinoma.
Methods
Data from 62 patients were retrospectively analyzed. Associations between histopathological factors (differentiation, stage, lymphatic invasion, blood vessel invasion, WPOI, and BD model) and regional control (RC) or disease‐free survival (DFS) were evaluated.
Results
The five‐year RC and DFS rates were 74% and 65%, respectively. Univariate analysis identified blood vessel invasion, lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, and BD model, as predictive factors for RC. Univariate analysis identified lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, as predictive factors for DFS.
Conclusion
The pathological invasion patterns should be considered when determining the follow‐up plan for patients with clinical N0 early oral tongue carcinoma.

American College of Surgeons National Surgical Quality Improvement Program assessment of risk factors for 30‐day unplanned readmission in patients undergoing head and neck surgery requiring free tissue reconstruction

16-01-2020 – Orly M. Coblens, Jason A. Brant, William W. Thomas, John P. Fischer, Jason G. Newman, Steven B. Cannady

Journal Article

Abstract
Background
Unplanned readmissions have become a metric for measuring quality of care. We analyzed the factors associated with 30‐day unplanned readmission (30d
UR) following head and neck cancer resections that included free tissue reconstruction (FTR).
Methods
The 2012‐2014 ACS‐National Surgical Quality Improvement Program (NSQIP) data set was queried. Univariate and multivariate logistic regression analyses were performed.
Results
Out of 1114 cases, 121 had a 30d
UR. The most common reasons were wound complications, including incisional infections, hematoma, and hemorrhage. A significant independent risk factor for 30d
UR included a clean/contaminated wound class (odds ratio OR, 2.27; 95% confidence interval CI, 1.20‐4.76). Patients receiving an osseous FTR had lower readmission rates (OR, 0.51; CI, 0.27‐0.91). Discharge destination had no statistical significance.
Conclusions
Based on the NSQIP data set, 10.9% of patients receiving an FTR for head and neck malignancy had a 30d
UR. Although large, population‐based data sets have limitations, these results elucidate that these patients are at an increased risk for unplanned readmissions, which can guide patient expectations and discharge planning.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo‐radiotherapy

16-01-2020 – Pierluigi Bonomo, Cinzia Talamonti, Isacco Desideri, Livia Marrazzo, Donato Pezzulla, Andrea Rampini, Silvia Bertocci, Roberta De Majo, Chiara Gasperi, Assunta Simona Curion, Luciana Lastrucci, Luca Dominici, Stefania Pallotta, Lorenzo Livi, Saverio Caini

Journal Article

Abstract
Background
We investigated whether the pattern of intensity‐modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD).
Methods
A frequency‐matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models.
Results
The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both).
Conclusion
Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patients surface may help predict the development of severe RD.

Safety and efficacy of transoral robotic and endoscopic thyroidectomy: The first 100 cases

16-01-2020 – Kyung Tae, Yong Bae Ji, Chang Myeon Song, Jeong Seon Park, Jung Hwan Park, Dong Sun Kim

Journal Article

Abstract
Background
The aim of this study was to evaluate the safety and efficacy of transoral robotic and endoscopic thyroidectomy.
Methods
We analyzed and compared the first 100 cases of transoral robotic (71 cases) and endoscopic (29 cases) thyroidectomy with 207 cases of conventional transcervical thyroidectomy.
Results
Transoral thyroidectomy was completed successfully in all patients, except for three who were converted to the robotic facelift or transcervical approach. The mean operative time of the transoral procedure was significantly longer than that of the conventional procedure. Perioperative complications such as hypoparathyroidism, vocal cord palsy, hematoma, and seroma did not differ between the two groups. However, there were some unusual complications such as CO2 embolism, surgical site infection, skin trauma, burn, and ecchymosis in transoral thyroidectomy. Postoperative cosmesis was significantly better in the transoral group.
Conclusion
Transoral robotic and endoscopic thyroidectomy is feasible and comparable to conventional transcervical thyroidectomy in highly selected patients.

Method of detection of thyroid nodules: correlation with frequency of fine‐needle aspiration and malignancy rate

16-01-2020 – Gary D. Rothberger, Melissa Cohen, Priya Sahay, Paula T. Szczepanczyk, Shahidul Islam

Journal Article

Abstract
Background
Thyroid nodules are commonly found by screening, and the clinical implications are unclear.
Methods
We retrospectively studied 460 patients who were evaluated for thyroid nodules. Medical records were queried to determine how the nodules were detected. We compared the rates of fine needle aspiration (FNA) and malignancy between nodules detected clinically, incidentally on imaging, or by screening.
Results
Nodules were detected clinically in 184 patients (40%), incidentally in 121 patients (26%), and by screening in 155 patients (34%). The rates of FNA and malignancy were lower for patients with nodules detected by screening (28% and 1%, respectively), compared to patients with clinically apparent nodules (75% and 15%) and patients with incidental nodules (69% and 8% P < .001).
Conclusion
Thyroid nodules detected via screening has a lower rate of FNA and is less likely to be diagnosed as a malignancy compared to nodules detected clinically or incidentally on imaging. Thyroid ultrasound examinations should be reserved for nodules that are clinically apparent or to evaluate nodules found incidentally on imaging.

Efficacy of EPA‐enriched supplement compared with standard formula on body weight changes in malnourished patients with head and neck cancer undergone surgery: a randomized study

16-01-2020 – Kitti Jantharapattana, Orachat Orapipatpong

Journal Article

Abstract
Background
Eicosapentaenoic acid (EPA) containing nutritional supplement can reverse weight loss and increase lean body mass in a perioperative period of patients with head and neck cancer. To study effects of an EPA‐enriched supplement compared with a conventional supplement in malnourished patients with head and neck cancer following surgery is primary objective.
Methods
The patients were randomized into EPA‐enriched and standard formula group. The supplements were prescribed 7 days preoperative through 14 days postoperative. Body weight and composition including serum parameters were measured from 7 days preoperative until 4 months postoperative. The hospitalized courses were recorded.
Results
Thirty‐one patients in each group consumed EPA‐enriched and standard formula supplements. There was no significant body weight or composition changes perioperative. No significant differences in the hospitalized days and postoperative complications was observed.
Conclusions
Body weight changes in malnourished patients with head and neck cancer following surgery were not influenced by EPA additives to perioperative nutritional supplements.

Prognostic capacity of Systemic Inflammation Response Index (SIRI) in patients with head and neck squamous cell carcinoma

16-01-2020 – Cristina Valero, Laura Pardo, Aina Sansa, Jacinto Garcia Lorenzo, Montserrat López, Miquel Quer, Xavier León

Journal Article

Abstract
Background
Inflammation and immune evasion are associated with carcinogenesis. Systemic Inflammation Response Index (SIRI) has been proposed as a pretreatment peripheral blood biomarker. The aim of this study is to analyze its prognostic capacity in head and neck squamous cell carcinomas (HNSCC).
Methods
We performed a retrospective study in 824 patients with HNSCC. SIRI was calculated by neutrophils*monocytes/lymphocytes. Using a recursive‐partitioning analysis considering disease‐specific survival (DSS) as dependent variable, three categories were defined according to SIRI value.
Results
Males, patients with history of toxic consumption, oropharyngeal or hypopharyngeal tumors, and advanced tumors had a significantly higher SIRI value. As SIRI increased, a significant decrease in DSS was observed. In a multivariable analysis, SIRI was an independent predictor of DSS. Moreover, SIRI was a significant predictor of local, regional, and distant recurrence‐free survival.
Conclusions
SIRI has independent prognostic capacity in HNSCC. Patients with higher SIRI have a significant decrease in DSS.

Alterations in genetic pathways following radiotherapy for head and neck cancer

16-01-2020 – Arash O. Naghavi, Youngchul Kim, George Q. Yang, Kamran A. Ahmed, Jimmy J. Caudell

Journal Article

Abstract
Background
Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).
We hypothesized there would be alterations in gene‐expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT‐naïve disease.
Methods
Patient data was abstracted from a prospectively maintained database. Linear‐microarray analysis and supervised gene‐set enrichment‐analysis were employed to compare RT‐naive and recurrent disease after prior‐RT.
Results
A total of 157 patients were analyzed, 96 (61%) were RT‐naive and 61 (39%) had RT.
After radiation, there was upregulation of genes associated with angiogenesis, protein‐translation‐machinery, cell‐cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).
Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B‐catenin‐pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024).
Conclusion
Patients with recurrences salvaged surgically post‐RT had significant alterations in gene‐expression and in Wnt/B‐catenin and MYC‐target pathways. These pathways may represent potential targets to prevent development of resistance to RT.

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

16-01-2020 – Li Wang, Liuqing Yang, Shichao Han, Jinming Zhu, Yuting Li, Zeming Wang, You‐Hong Fan, Eric Lin, Ruiping Zhang, Narayan Sahoo, Yupeng Li, Xiaodong Zhang, Xiaochun Wang, Tengfei Li, Xiaorong R. Zhu, Hongtu Zhu, John V. Heymach, Jeffrey N. Myers, Steven J. Frank

Journal Article

Abstract
Background
Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear.
Methods
Proteomics analyses of protein expression profiles by reverse‐phase protein arrays were done for two human papillomavirus HPV‐negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested.
Results
Compared with PRT, XRT tended to induce lower expression of DNA damage repair—and cell cycle arrest‐related proteins and higher expression of cell survival‐ and proliferation‐related proteins.
Conclusions
Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.

TRPV1 regulates inflammatory process in the tongue of surgically induced xerostomia mouse

16-01-2020 – Min H. Yoo, Yun‐Hee Rhee, JaeYun Jung, Sang‐Joon Lee, Jung‐Hwan Moon, Ji‐Hun Mo, Phil‐Sang Chung

Journal Article

Abstract
Background
The aim of study is to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on xerostomia‐induced inflammatory response in vivo.
Methods
Parotid, submandibular, and lingual gland were removed for xerostomia induction. The expression of inflammatory cytokines, TRPV1, NFk
B, and MAPK in xerostomia was evaluated and compared in both TRPV1 wild and knockout mice.
Results
The level of interleukin‐6 (IL‐6) and IL‐17, neutrophil/CD4 T‐cell infiltration, phosphorylation of extracellular signal‐regulated kinase (ERK) and c‐Jun N terminal kinase, TRPV1, and the localization of NFk
B were elevated in xerostomia‐induced TRPV1 wild‐type mice. In contrast, inflammatory cytokines and MAPK were decreased in xerostomia‐induced TRPV1 knockout mice. TRPV1 antagonist treatment also reduced tongue ulceration, neutrophil/CD4+ T‐cell expression, IL‐6, and IL‐17 in TRPV1 wild‐type mice.
Conclusion
TRPV1 had a crucial role in modulating inflammation in xerostomia and targeting TRPV1 might be a promising therapeutic strategy for xerostomia.

Prognostic significance of MTOR expression in HPV positive and negative head and neck cancers treated by chemoradiation

16-01-2020 – Thomas G. Wilson, Alaa Hanna, Johnathon Recknagel, Barbara L. Pruetz, Andrew M. Baschnagel, George D. Wilson

Journal Article

Abstract
Background
The mechanistic target of rapamycin (MTOR) plays a key role in regulating cell growth and metabolism and is commonly overexpressed in head and neck cancer (HNSCC). This study investigated the association of MTOR with clinical outcome in human papilloma virus (HPV) positive and negative HNSCC patients treated by chemoradiation.
Methods
A tissue microarray (TMA) consisting of cores from 109 HNSCC patients treated by definitive chemoradiation was constructed and stained with antibodies against p16 and MTOR and expression correlated with clinicopathological features and clinical outcome.
Results
MTOR varied widely between tumor cores and was not associated with HPV status or clinicopathological features. There was a positive correlation with pre‐treatment FDG uptake.(P = .01). In HPV negative patients, MTOR predicted for shorter locoregional control (P = .02), diseases free survival (P = .02), and overall survival (P = .04). MTOR expression was not associated with outcome in HPV positive patients.
Conclusions
Prognostic significance of MTOR expression depends on HPV status.

Dose volume effects of re‐irradiation for locally recurrent nasopharyngeal carcinoma

16-01-2020 – Wai‐Tong Ng, Michael CH Lee, Nelson TC Fung, Edwin CY Wong, Alice KW Cheung, James CH Chow, Kwok‐Hung Au, Darren MC Poon, Jessica WY Lai, Chi‐Leung Chiang, Horace CW Choi, Tin‐Ching Chau, Victor HF Lee, Anne WM Lee

Journal Article

Abstract
Background
This study analyzed the dose volume effects of re‐irradiation for locally recurrent nasopharyngeal carcinoma (NPC) and attempts to determine the optimal dose for the best survival.
Methods
Ninety‐one patients were studied. The local control, fatal complication, and overall survival were analyzed against the dose (in Equivalent Dose at 2 Gy/fractions) and recurrent gross tumor volume (GTV).
Results
The local control and fatal complication rate appear to increase with prescribed dose. The overall survival peaks at around 60 Gy10. Local control decreases significantly with increasing GTV (P < .001) while overall survival shows similar trend (P = .06). No correlation was observed between the fatal complication rate and GTV volume. The dose response of local control appears to be stronger for smaller tumors.
Conclusion
GTV volume plays a significant role in local control. A 60 Gy10 appears to be optimal for the best survival outcome; higher doses might be considered for small tumors.

Reply to the letter of the editor: Is tailored management better than salvage in laryngeal squamous cell carcinomas?

16-01-2020 – Ximena Mimica, Martin Hanson, Marc A. Cohen

Letter

Is tailored management better than salvage in laryngeal squamous cell carcinomas

16-01-2020 – Bhargaw Ilapakruty, Vishal U. S. Rao

Letter

Issue Information

16-01-2020 –

Inside Front Cover

16-01-2020 –

The inside front cover image is based on the Original Article Closure of radial forearm free flap donor site: A comparative study between keystone flap and skin graft by Pauline Potet MD et al., https://doi.org/10.1002/hed.25977.

Front Cover

16-01-2020 –

The outside front cover image is based on the Original Article Minimally invasive surgery for laryngopharyngeal cancer: a multicenter feasibility study of a combination strategy involving transoral surgery and real‐time indocyanine green fluorescence‐navigated sentinel node navigation surgery by Koji Araki MD et al., https://doi.org/10.1002/hed.25993.

Back Cover

16-01-2020 –

The outside back cover image is based on the Original Article Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical No early oral tongue carcinoma by Yukiko Hori et al., https://doi.org/10.1002/hed.25994.
Cover image © Kenya Kobayashi Images.

The surgical treatment of cerebrospinal fistula: Qualitative and quantitative analysis of indications and results

16-01-2020 – Alessandra Iavarone, Paolo Luparello, Maria Silvia Lazio, Lara Valentina Comini, Federica Martelli, Oliviero De Luca, Giovanni Paolo Santoro, Roberto Santoro, Giammarco Alderotti, Giuditta Mannelli

Journal Article, Review

Abstract
Cerebrospinal fistula might occur in different ways. CSF closure techniques have undergone significant evolution that has led to the consolidation of the transnasal endoscopic approach. Despite the existence of multiple publications, meaningful information is still lacking in clinical practice and the literature about the ideal method, material, and timing for repair of CSF. The purpose of this review was to summarize the success rate of endoscopic CSF leak repair as well as whether specific techniques or materials influence the primary success rate through a review of the latest advancements in endoscopic CSF management published in the past 10 years. The principles of multilayer reconstructions and the routine use of vascularized flaps in expanded endonasal surgery have reduced postoperative CSF leaks failure rates between 5% and 10% (4% in this meta‐analysis). Effective endoscopic anterior skull base (ASB) closure may be achieved by multiple reconstructive techniques, which should be tailored case by case according to the patient and defect conditions.

Oncological impact of hypothyroidism and levothyroxine supplementation following hemithyroidectomy in patients with papillary thyroid carcinoma

13-01-2020 – Dongbin Ahn, Gil J. Lee, Jin H. Sohn, Jae H. Jeon

Journal Article

Abstract
Background
We aimed to evaluate the oncological impact of hypothyroidism and levothyroxine (LT) supplementation after hemithyroidectomy in patients with papillary thyroid carcinoma (PTC).
Methods
We retrospectively examined 401 patients who underwent hemithyroidectomy for classic PTC and who were postoperatively followed‐up with ≥3 thyroid function measurements for ≥24 months.
Results
During 77.4 months of follow‐up, 268/401 patients (66.8%) developed hypothyroidism and 19/401 patients (4.7%) showed recurrence. Recurrence rates did not differ between the euthyroidism and hypothyroidism development groups. Recurrence rates were significantly lower in the LT group than in the no‐LT group, although mean postoperative thyroid‐stimulating hormone (TSH) levels were not different between the two groups. Univariate and multivariate analysis showed that tumors sized >1 cm and lack of LT supplementation were significantly associated with recurrence.
Conclusions
Postoperative hypothyroidism development was not a risk factor for PTC recurrence after hemithyroidectomy. Nevertheless, LT supplementation reduced recurrence risk without suppressing TSH.

Clincopathological characteristics and treatment outcomes of oral leukoplakia by carbon dioxide laser excision in the elderly patients

13-01-2020 – Shih‐Wei Yang, Yun‐Shien Lee, Liang‐Che Chang, Cheng‐Cheng Hwang, Tai‐An Chen

Journal Article

Abstract
Background
Older age is one of the factors associated with malignant transformation of oral leukoplakia (OL). The purpose of this study is to analyze the clincopathological features and treatment outcomes of OL in the elderly patients.
Methods
The demographic data and histopathological results of the patients (age ≥ 65) who received carbon dioxide laser surgery for OL from 2002 to 2017 were analyzed statistically.
Results
There were 53 males and 16 females, with a mean age 71.2 ± 4.9. The follow‐up time was 42.5 ± 35.2 months. In the univariate analysis, morphology, pathology, and area were found to be factors associated with postoperative recurrence. Among these factors, pathology and area were the independent predictive factors for recurrence in the multivariate logistic regression model. Malignant transformation occurred in 8 of 69 patients (11.6%).
Conclusions
The pathological high‐risk dysplasia and area of OL were the two prognostic factors for postoperative recurrence.

Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer

11-01-2020 – Junli Shi, Soo Yee Tan, Andrea Zhe Ern Lee, Siting Zhang, Swarnalatha Lucky Sasidharan, Benjamin Wong, Min Han Tan, Chwee Ming Lim

Journal Article

Abstract
Background
Restoring apoptosis dysregulation via survivin inhibition has been investigated in several cancers. In Epstein‐Barr Virus (EBV)‐driven nasopharyngeal cancer (NPC), virally induced oncogenes can upregulate survivin. Therefore, we seek to investigate the therapeutic efficacy of YM‐155 (a survivin inhibitor) in NPC, both in vitro and in vivo models.
Methods
Cytotoxicity, apoptosis, and active‐caspase 3 expression assays were performed.
Results
Both NPC tissue and cells expressed high levels of survivin which were inhibited by YM‐155 in a dose‐dependent manner. In addition, YM‐155 induced apoptosis of NPC cells with an IC50 of 100 nM and inhibited tumor growth in vivo (P < 0.05). YM‐155 in combination with cisplatin or radiation significantly increased overall cytotoxicity as compared to YM‐155 monotherapy. In the xenograft model, YM‐155 plus radiation additively achieved significantly higher percentage of active‐caspase 3‐positive tumor cells than radiation alone (P < 0.05).
Conclusions
YM‐155 is a potential therapeutic agent for NPC through inhibiting survivin and restoring apoptosis dysregulation.

Survivorship support in head and neck cancer: American Head and Neck Society survey

10-01-2020 – David M. Cognetti, Victoria M. Villaflor, Carole Fakhry, Matthew C. Miller, Kelly M. Malloy

Journal Article

Abstract
Background
The value of supporting cancer survivors beyond formal treatment has become increasingly recognized among clinicians who care for patients with head and neck cancer.
Methods
A survey was developed by the American Head and Neck Society (AHNS) Survivorship Committee and distributed to members of the AHNS electronically.
Results
The survey was distributed to 1403 AHNS members, with 202 responses (14.4%). Among survivorship topics, respondents were most likely to address detection of recurrence/second primary malignancies (97.5%), dysphagia (93.1%), and thyroid function (90.1%) with their patients; they were least likely to address sleep disturbance/apnea (27.7%) and body and self‐image issues (29.7%.) Less than half provide patients with a written treatment summary (43.1%) or follow‐up care plan (36.9%).
Conclusions
These results highlight the need for improved survivorship care planning and offer an opportunity for the development of educational and survivorship research in head and neck cancer care.

Elective neck treatment in sinonasal undifferentiated carcinoma: Systematic review and meta‐analysis

10-01-2020 – Muhammad Faisal, Rudolf Seemann, Claudia Lill, Sasan Hamzavi, Arno Wutzl, Boban M. Erovic, Stefan Janik

Journal Article, Review

Abstract
Sinonasal undifferentiated carcinomas (SNUCs), being an aggressive malignancy with dismal survival outcome, have given limited consideration regarding management of regional failures. A total of 12 studies, published between 1999 and 2019, met inclusion criteria. We performed a meta‐analysis assessing regional (neck) relapse after elective neck treatment compared to observation in clinically node negative (N0) necks. Clinical data of 255 patients were used for meta‐analysis. Among them, 83.4% of patients presented with T4 tumors and 14.1% had positive neck nodes. Elective neck treatment was applied in 49.5% of analyzed patients. Regional relapses occurred in 3.7% of patients who have undergone elective neck treatment compared to 26.4% in patients who had not. Elective neck treatment significantly reduced the risk of regional recurrence (odds ratio 0.20; 95% confidence interval 0.08‐0.49; P = .0004). The meta‐analysis indicates that elective neck treatment could significantly reduce the risk of regional failures in patients with SNUCs.

Hepatocyte Growth Factor Receptor overexpression predicts reduced survival but its targeting is not effective in unselected HNSCC patients

10-01-2020 – Martin Khan, Sami S. Khaznadar, Johannes Routila, Sami Ventelä, Elke Schmid, Bastian Gebhart, Eva T. Becker, Helge G. Roider, Merja Perala, Arndt A. Schmitz, Thomas Krahn, Oliver Ahsen

Journal Article

Abstract
Background
MET has emerged as target in head and neck squamous cell carcinoma (HNSCC). However, clinical data on MET inhibition in HNSCC are limited.
Methods
HNSCC biopsies and cell lines were tested for MET activity. The response of cell lines to BAY‐853474 was tested in proliferation assays. The prognostic value of MET expression was also analyzed.
Results
HNSCC cell lines do not respond to MET inhibition. MET‐dependent gastric cancer cell lines have much higher levels of MET expression and phosphorylation than HNSCC cell lines. Clinical samples of HNSCC contain much less MET than responsive models.
Conclusions
No clinical response to MET inhibitors in monotherapy may be expected in unselected cases of HNSCC. Only selected patients with MET amplifications should be treated with MET inhibitors. Patients with increased MET immunoreactivity have shorter overall survival. MET might be useful as marker for the detection of patients with more aggressive types of HNSCC.

Perceived value drives use of routine asymptomatic surveillance PET/CT by physicians who treat head and neck cancer

10-01-2020 – Benjamin R. Roman, Shivangi Lohia, Nandita Mitra, Marilene B. Wang, Anna M. Pou, F. Christopher Holsinger, David Myssiorek, David Goldenberg, David A. Asch, Judy A. Shea

Journal Article

Abstract
Background
Why physicians use surveillance imaging for asymptomatic cancer survivors despite recommendations against this is not known.
Methods
Physicians surveilling head and neck cancer survivors were surveyed to determine relationships among attitudes, beliefs, guideline familiarity, and self‐reported surveillance positron‐emission‐tomography/computed‐tomography use.
Results
Among 459 responses, 79% reported using PET/CT on some asymptomatic patients; 39% reported using PET/CT on more than half of patients. Among attitudes/beliefs, perceived value of surveillance imaging (O.
R. 3.57, C.
I. 2.42‐5.27, P = <.0001) was the strongest predictor of high imaging, including beliefs about outcome (improved survival) and psychological benefits (reassurance, better communication). Twenty‐four percent of physicians were unfamiliar with guideline recommendations against routine surveillance imaging. Among physicians with high perceived‐value scores, those less familiar with guidelines imaged more (O.
R. 3.55, C.
I. 1.08‐11.67, P = .037).
Conclusions
Interventions to decrease routine surveillance PET/CT use for asymptomatic patients must overcome physicians misperceptions of its value. Education about guidelines may modify the effect of perceived value.

Palliative chemotherapy with or without cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck: Indian tertiary care retrospective analysis

08-01-2020 – Ankur Bahl, Komal Bhatia, Pragati Choudhary, Suhas Singhla, Gunjan Shrivastava, Jaspriya Bal, Anil K. Anand, Harit Chaturvedi, Bharat Dua

Journal Article

Abstract
Background
We report our experience with Indian patients who received palliative chemotherapy with/without cetuximab for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Methods
Data from 229 R/M SCCHN patients treated with cetuximab and chemotherapy (n = 140) or chemotherapy alone (n = 89) were retrospectively analyzed for response rate (RR), progression‐free survival (PFS), overall survival (OS), and safety.
Results
Patients receiving cetuximab with chemotherapy demonstrated significant increase in RR (77.1% vs 44.9%, P = .0001), PFS (8.1 vs 6.1 months, P = .039), and OS (11.8 vs 8.0 months, P = .002) compared with patients receiving chemotherapy alone. Continuing cetuximab and changing chemotherapy combination (second line and beyond) in fit patients doubled OS (13.5 vs 6.1 months, P = .001). Adverse effects, except skin reactions (more in the cetuximab with chemotherapy group; P = .001), were similar in both groups.
Conclusion
Adding cetuximab to chemotherapy improved ORR, PFS, and OS in Indian R/M SCCHN patients, and cetuximab was well tolerated.

Defining a cohort of oligometastatic nasopharyngeal carcinoma patients with improved clinical outcomes

07-01-2020 – Jeremy Chee, Xuandao Liu, Donovan Eu, Thomas Loh, Francis Ho, Lea C. Wong, Ivan Tham, Chee S. Tan, Boon C. Goh, Chwee M. Lim

Journal Article

Abstract
Objectives
To compare the clinical outcomes of oligometastatic versus widely metastatic NPC patients.
Materials and Methods
Retrospective review of 157 patients with metastatic NPC at a tertiary hospital was performed. Multivariate analysis was carried out to compare the overall and progression‐free survival (OS and PFS) of these two cohorts of NPC patients. The number of organ involvement and discrete metastatic lesions associated with improved OS and PFS were ascertained.
Results
Patients with oligometastatic NPC (single organ, less than six discrete metastatic lesions) had a better median OS than patients with widespread metastasis (24.8 versus 12.8 months, P < .001). Similarly, the median PFS of oligometastatic NPC was better than that of polymetastatic NPC (11.7 versus 7.3 months, P < .001).
Conclusion
Single organ disease with less than six discrete lesions is a good indicator of limited metastatic load in NPC, and is associated with improved survival.

Prophylactic swallowing therapy for patients with head and neck cancer: A three‐arm randomized parallel‐group trial

06-01-2020 – Laurelie R. Wall, Elizabeth C. Ward, Bena Cartmill, Anne J. Hill, Elizabeth Isenring, Joshua Byrnes, Sandro V. Porceddu

Journal Article

Abstract
Background
Intensive prophylactic swallowing therapy can mitigate dysphagia in patients with oropharyngeal (OP) SCC, however, presents service challenges. This trial investigated the clinical efficacy of three service models delivering prophylactic swallowing therapy during (chemo)radiotherapy (CRT).
Methods
Patients (n = 79) with OPSCC receiving (C)RT were were randomized to: (a) clinician‐directed face‐to‐face therapy (n = 26); (b) telepractice therapy via “Swallow
IT” (n = 26); or (c) patient self‐directed therapy (n = 27). Swallowing, nutritional, and functional status were compared at baseline, 6‐weeks, and 3‐months post‐(C)RT. Patients perceptions/preferences for service‐delivery were collated posttreatment.
Results
Service‐delivery mode did not affect clinical outcomes, with no significant (P > .05) between‐group differences or group‐by‐time interactions observed for swallowing, nutrition, or functional measures. Therapy adherence declined during (C)RT in all groups. Swallow
IT and clinician‐directed models were preferred by significantly (P = .002) more patients than patient‐directed.
Conclusions
Swallow
IT provided clinically equivalent outcomes to traditional service models. Swallow
IT and clinician‐directed therapy were preferred by patients, likely due to higher levels of therapy support.

Prevalence of NUT carcinoma in head and neck: Analysis of 362 cases with literature review

06-01-2020 – Taebum Lee, Junhun Cho, Chung‐Hwan Baek, Young‐Ik Son, Han‐Sin Jeong, Man Ki Chung, Sang Duk Hong, Yong Chan Ahn, Dong Ryul Oh, Jae Myoung Noh, Keunchil Park, Myung‐Ju Ahn, Hyung‐Jin Kim, Yi Kyung Kim, Young Hyeh Ko

Journal Article

Abstract
Background
Nuclear protein in testis (NUT) carcinoma is a poorly differentiated carcinoma defined by the presence of NUT gene rearrangement. In the head and neck, the true prevalence of NUT carcinoma is unknown.
Methods
We retrospectively investigated NUT expression with clinicopathologic features in 362 patients of poorly differentiated or undifferentiated carcinomas in the head and neck, and reviewed the literature reports.
Results
Four (4/362, 1.1%) cases showed strong nuclear expression for NUT‐specific monoclonal antibody, and all these tumors were in the sinonasal tract (4/40, 10%). The clinical outcome and histology were diverse unlike previously described. Although previous studies reported different frequency results according to study subjects, frequencies in sinonasal tract are relatively constant (10/80, 12.5%).
Conclusions
This is the largest study on the prevalence of NUT carcinoma in head and neck areas. It is important to include in the differential diagnosis of poorly differentiated carcinoma, particularly in the sinonasal tract.

Methotrexate plus or minus cetuximab as first‐line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib‐randomized phase II study Commence

06-01-2020 – Janneke C. Ham, Esther Meerten, W. Edward Fiets, Laurens V. Beerepoot, Frank J. F. Jeurissen, Marije Slingerland, Marianne A. Jonker, Olga Husson, Winette T. A. Graaf, Carla M. L. Herpen

Journal Article

Abstract
Background
Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression‐free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS.
Methods
In the phase‐Ib‐study, patients with R/M SCCHN received methotrexate and cetuximab as first‐line treatment. The primary objective was feasibility. In the phase‐II‐study patients were randomized to this combination or methotrexate alone (2:1). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), toxicity, and quality of life (QoL).
Results
In six patients in the phase‐Ib‐study, no dose limiting toxicities were observed. In the phase II study, 30 patients received the combination and 15 patients methotrexate. In the phase‐II‐study median PFS was 4.5 months in the combination group vs 2.0 months in the methotrexate group (HR 0.37; P = .002). OS, toxicity, and QoL were not significantly different.
Conclusion
Cetuximab with methotrexate improved PFS without increased toxicity in R/M SCCHN‐patients.

Postimplantation radiation therapy in head and neck cancer patients: Literature review

03-01-2020 – Carine Koudougou, Hélios Bertin, Bastien Lecaplain, Zahi Badran, Julie Longis, Pierre Corre, Alain Hoornaert

Journal Article, Review

Abstract
There is no recommendation regarding the timing for implant surgery in patients with head and neck cancer (HNC) who require postoperative radiation therapy (RT). This systematic review focused on the literature about the outcomes of implants placed during ablative surgery in patients with HNC who underwent postoperative RT. Implants placed after radiation therapy and implants placed in reconstructed jaws were excluded. Four comparative studies involving 755 native mandible primary implants were analyzed. The survival rate with postimplantation RT was 89.6% vs 98.6% in patients with no additional radiation. The overall success of implant‐retained overdenture in patients with RT performed postimplantation was 67.4% vs 93.1% in patients with implant surgery that was carried out 1 year after the completion of radiation therapy. Only five cases of osteoradionecrosis (ORN) of the jaw were reported. The outcomes for implant survival rates appear to be positive for irradiated implants.

Analysis of patients who decline treatment for squamous cell carcinoma of the head and neck: National perspective

02-01-2020 – Christopher B. Sullivan, Zaid Al‐Qurayshi, Nitin A. Pagedar

Journal Article

Abstract
Background
To analyze demographic and socioeconomic factors that influence patients decisions to decline treatment for head and neck squamous cell carcinoma (SCC).
Methods
Retrospective cohort analysis utilizing the National Cancer Data Base of patients with oral cavity/oropharyngeal, hypopharyngeal, and laryngeal SCC.
Results
A total of 166 204 patients were included, of which 689 patients declined all treatment. Among early‐stage (I‐II) patients, Charlson/Deyo score ≥ 3, hypopharyngeal cancer, and no insurance or Medicare were more likely to decline all recommended treatment (P < .05). Among advanced stage (III‐IV) patients, females (odds ratio 1.27, 95% confidence interval 1.05‐1.53; P = .013), Charlson Deyo score ≥ 1, non‐oral cavity cancers, and closer distance between patients area of residence from treating facility were more likely to decline all treatment (P < .05).
Conclusions
Female patients and patients with no insurance, Medicare, or Medicaid are more likely to decline recommended treatment for SCC of the head and neck. Educational status is not predictive of declining treatment.

The role of a post therapeutic surveillance program for sinonasal malignancies: Analysis of 417 patients

31-12-2019 – Jacopo Zocchi, Giacomo Pietrobon, Isotta Campomagnani, Emilia Riggi, Giovanni Veronesi, Rossana Borchini, Raul Pellini, Luca Volpi, Maurizio Bignami, Paolo Castelnuovo

Journal Article

Abstract
Background
Post therapeutic surveillance of head and neck neoplasms is a still debated issue in the current literature: although different works tried to establish frequency, modality, and efficacy of a routine follow‐up, little evidence has been produced, in particular considering only sinonasal malignancies.
Methods
A retrospective review of patients treated for sinonasal malignancies in a single tertiary center and followed through a regular program of follow‐up was carried out. Rate of recurrence, location, timing, diagnosis, and salvage treatment were the main data analyzed.
Results
Of note, 417 patients were included in the study and 117 experienced at least one relapse. Staging, histological type, and previous treatment represent the main clinical factors to be considered to stratify patients risk of recurrence.
Conclusion
A regular post therapeutic surveillance can provide an early recurrence detection for patients treated for sinonasal malignancies, offering opportunity for salvage treatment in a high percentage of patients.

ERRATUM

30-12-2019 –

Social participation in head and neck cancer survivors with swallowing disorder: World Health Organization Disability Assessment Schedule 2.0 study

30-12-2019 – Yu‐Hao Lee, Shari Goo‐Yoshino, Henry L. Lew, Wen‐Chou Chi, Chia‐Feng Yen, Hua‐Fang Liao, Shih‐Ching Chen, Tsan‐Hon Liou

Journal Article

Abstract
Background
Social function and quality of life were negatively impacted by the sequelae of treatment for the disease in the head and neck cancer survivor with swallowing disorder.
Method
Data from a total of 1023 survivors between July 2012 and November 2017 were collected from the Taiwan Data Bank of Persons with Disability. Nonparametric rank F test was used to analyze the influence of different variables on social participation.
Results(a) All WHODAS (World Health Organization Disability Assessment Schedule) 2.0 scores revealed significantly increased difficulty when swallowing impairment increased (P < .001). (b) Unemployment, institutionalization, severity of swallowing impairment, cancer sites, and WHODAS 2.0 score of domains 1 to 4 were negatively related to social participation, while living in rural area is related to increased social participation.
Conclusions
Social participation was negatively affected by many variables in this population. Among these variables, cancer sites and WHODAS 2.0 score of domains 1 to 4 were the strongest factors.

Comparing postoperative outcomes after free flap surgery in a specialty step‐down unit vs nonspecialty intensive care unit

30-12-2019 – Shiayin F. Yang, William Adams, Gina E. Lazzara, Eric J. Thorpe, Amy L. Pittman

Journal Article

Abstract
Background
To determine if there was a difference in postoperative outcomes of head and neck free flap reconstruction patients treated in a specialty step‐down unit compared to a nonspecialty intensive care unit (ICU).
Methods
A retrospective review was performed of all patients who underwent free flap reconstruction for head and neck defects from 2014 to 2017 at Loyola University Medical Center. Patients managed postoperatively in the ICU were compared to patients managed in a specialty step‐down unit. Postoperative outcomes, length of stay, and readmission were compared.
Results
Three hundred and five patients were included in the study. Patients managed postoperatively in the specialty step‐down unit had comparable rates of postoperative complications and flap failure as ICU patients. Step‐down patients had significantly shorter lengths of stay (Mdn = 5 days, IQR = 5‐7 days) than patients in the ICU (Mdn = 6 days, IQR = 5‐6 days; P < .001).

Pseudomonas aeruginosa‐mannose sensitive hemagglutinin injection therapy for the treatment of chyle fistula following neck dissection

28-12-2019 – Qiang Chen, Xiuhe Zou, Yu Ma, Feng Liu, Tao Wei, Zhihui Li, Rixiang Gong, Jingqiang Zhu

Journal Article

Abstract
Background
The efficacy of Pseudomonas aeruginosa‐mannose sensitive hemagglutinin (PA‐MSHA) injection therapy in the treatment of chyle fistula following neck dissection is unclear.
Methods
This prospective study enrolled 26 patients who developed chyle fistula after neck dissection. Patients were divided into high‐output (>500 m
L) and low‐output groups (≤500 m
L) and were initially treated conservatively for 5 days in the high‐output group or 7 days in the low‐output group. When conservative treatment failed, topical PA‐MSHA therapy was applied.
Results
Twelve of 26 patients were cured with conservative treatment, and the remaining 14 patients were all successfully resolved by PA‐MSHA therapy. Chyle fistula got resolved in the low‐output and high‐output groups after the initiation of therapy were at a median 1 days and 6 days, respectively. Among them, 12 (85.7%) patients experienced fever and 11 (78.6%) patients experienced neck pain.
Conclusions
Topical PA‐MSHA injection therapy could effectively manage chyle fistula following neck dissection.

Prevalence of profound laryngeal sensory neuropathy in head and neck cancer survivors with feeding tube‐dependent oropharyngeal dysphagia

27-12-2019 – Omid B. Mehdizadeh, Shumon I. Dhar, Lisa Evangelista, Nogah Nativ‐Zeltzer, Arnaud F. Bewley, Peter C. Belafsky

Journal Article

Abstract
Background
Laryngopharyngeal sensory neuropathy (LSN) has been observed to be a contributing factor to swallowing dysfunction in head and neck cancer (HNC) survivors.
Methods
Retrospective review of 43 tube‐dependent HNC survivors was conducted. LSN was assessed with direct palpation of the aryepiglottic fold and by traversing the true vocal folds without eliciting a cough reflex with a flexible laryngoscope.
Results
The primary tumor sites were oropharynx (51%), larynx (14%), nasopharynx (4.7%), oral cavity (14%), thyroid (4.7%), unknown primary (9.3%), and esophagus (2.3%). The prevalence of profound LSN was 79.1%. Objective fluoroscopic parameters contributing to swallowing dysfunction were diminished laryngohyoid elevation (100%), pharyngeal weakness (67%), and reduced lateral PES opening (37%).
Conclusions
The prevalence of LSN in HNC survivors with feeding tube‐dependent dysphagia is high (79.1%). The data suggest that LSN, in addition to fibrosis, pharyngoesophageal stenosis, and cranial nerve motor deficits contributes to swallowing dysfunction in these patients.

Anatomy based corridors to the infratemporal fossa: Implications for endoscopic approaches

27-12-2019 – Lifeng Li, Nyall R. London, Daniel M. Prevedello, Ricardo L. Carrau

Journal Article

Abstract
Background
The infratemporal fossa (ITF) represents an area densely packed with neurovascular structures within irregular boundaries. The goal of this study was to classify the ITF into zones corresponding to its anatomical spaces and the order in which they are encountered during an endonasal approach (anteroposterior axis).
Methods
Six cadaveric specimens (12 sides) with injected colored latex were dissected. Following an endoscopic medial maxillectomy and Denkers approach, a progressive exploration of the masticator space and upper parapharyngeal space was completed. A classification of the ITF based on well‐defined spaces was ascertained.
Results
The ITF was divided into five zones:Zone 1 (retromaxillary space)—space lying between the posterolateral wall of the maxillary sinus and the temporalis and pterygoid muscles.
Zone 2 (superior interpterygoid space)—area including the superior head of the lateral pterygoid muscle, V3, and foramen ovale.
Zone 3 (inferior interpterygoid space)—includes the inferior head of lateral pterygoid muscle, medial pterygoid, and temporalis muscles, and the space enclosed by these muscles.
Zone 4 (temporo‐masseteric space)—space lateral to the temporalis muscle (comprising fat mostly).
Zone 5 (tubopharyngeal space)—includes the Eustachian tube, tensor, and levator veli palatini muscles, and structures in upper parapharyngeal space.
Conclusion
The ITF can be visualized as five zones based on spaces enclosed by the masticator muscles and upper parapharyngeal structures. This novel classification system is useful to guide endoscopic approaches to the ITF, while decreasing the potential for injury of neurovascular structures and pterygoid muscles.

Pilot study for a novel and personalized voice restoration device for patients with laryngectomy

26-12-2019 – Anaïs Rameau

Journal Article

Abstract
Background
The main modalities for voice restoration after laryngectomy are the electrolarynx, the tracheoesophageal puncture and esophageal speech. All have limitations and new technologies may offer innovative alternatives via silent speech.
Objective
To describe a novel and personalized method of voice restoration using machine learning applied to electromyographic signal from articulatory muscles for the recognition of silent speech in a patient with total laryngectomy.
Methods
Surface electromyographic (s
EMG) signals of articulatory muscles were recorded from the face and neck of a patient with total laryngectomy who was articulating words silently. These s
EMG signals were then used for automatic speech recognition via machine learning. Sensor placement was tailored to the patients unique anatomy, following radiation and surgery. A personalized wearable mask covering the sensors was designed using 3D scanning and 3D printing.
Results
Using seven s
EMG sensors on the patients face and neck and two grounding electrodes, we recorded EMG data while he was mouthing “Tedd” and “Ed.” With data from 75 utterances for each of these words, we discriminated the s
EMG signal with 86.4% accuracy using an XGBoost machine‐learning model.
Conclusions
This pilot study demonstrates the feasibility of s
EMG‐based alaryngeal speech recognition, using tailored sensor placement and a personalized wearable device. Further refinement of this approach could allow translation of silently articulated speech into a synthesized voiced speech via portable devices.

Endoscopic resection of sinonasal malignancies

24-12-2019 – Ahmed S. Abdelmeguid, Shaan M. Raza, Shirley Y. Su, Michael Kupferman, Dianna Roberts, Franco DeMonte, Ehab Y. Hanna

Journal Article

Abstract
Background
In this study, we evaluate our experience and the outcomes of patients with sinonasal cancer treated with endoscopic resection.
Methods
Retrospective review of patients with sinonasal cancer who had endoscopic resection was conducted. The outcomes of interest included survival outcomes and surgical complications.
Results
Overall, 239 patients were included. Median follow up time was 46.6 months. Of the 239 patients, 167 (70%) had a pure endonasal endoscopic approach, while 72 (30%) had an endoscopic‐assisted approach. Postoperative cerebrospinal fluid (CSF) leakage occurred in 14 patients (5.9%). Negative margins were achieved in 209 patients (87.4%). There was no significant difference in the margin status between the pure endoscopic and endoscopic‐assisted group (P = .682). There was no significant difference in the survival outcomes between both the groups.
Conclusion
Our data suggest that in properly selected patients, endoscopic approaches have acceptable morbidity with low complication rates and can provide an oncologically sound alterative to open approaches.

Analysis of patterns and risk factors regarding the onset of nodules in the contralateral thyroid lobe during follow‐up ultrasonography among patients after unilateral lobectomy for the treatment of papillary thyroid carcinoma

24-12-2019 – Chao Sun, Qian Wang, Qianqian Guo, Qing Chang, Xin Liang, Dong Wang, Hongbin Dai, Zhiguang Hu, Tianyu Xu, Wenqi Feng, Zhengjiang Li, Lijuan Niu

Journal Article

Abstract
Background
This study tries to find the patterns of new nodules in contralateral thyroid lobe among papillary thyroid carcinomas (PTCs) after lobectomy using ultrasonography.
Methods
Of note, 456 PTCs were enrolled. Clinicopathological features of primary tumors and sonographic patterns of new nodules in contralateral lobe were documented. Logistic regression analysis was performed to identify risk factors for new nodules.
Results
The overall incidence of new nodules was 41.9%. 96.3% of new nodules were no greater than 1 cm while only 10.5% of those were with high suspicion of malignancy. There was no difference in the incidence and sonographic patterns of new nodules between patients with an original tumor size <1 cm (n = 267) vs 1 to 4 cm (n = 189). Multivariate logistic regression analysis showed age (OR, 1.021; 95% CI, 1.001‐1.041; P = .036) played risk factor for new nodules while tumor size >1 cm did not.
Conclusion
New nodules in the contralateral lobe were common, but usually small and benign by ultrasound features. Older age was found to be a risk factor to predict new nodules. This study supports lobectomy for 1‐4 cm PTC in terms of incidence of new nodules on the remnant lobe.

A prospective evaluation of health‐related quality of life after skull base re‐irradiation

23-12-2019 – Houda Bahig, Sweet P. Ng, Courtney Pollard, Theresa P. Nguyen, Gary B. Gunn, David I. Rosenthal, Clifton D. Fuller, Steven J. Frank, Adam S. Garden, Jay P. Reddy, William H. Morrison, Renata Ferrarotto, Ehab Y. Hanna, Franco DeMonte, Shirley Y. Su, Jack Phan

Journal Article

Abstract
Purpose
To report cancer control outcomes and health‐related quality of life (HRQoL) outcomes after highly conformal skull‐based re‐irradiation (re‐RT).
Methods
Patients planned for curative intent re‐RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI‐BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires.
Results
Thirty‐nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow‐up was 14 months. Progression free survival was 71% at 1‐year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI‐BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow‐ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous.
Conclusion
Conformal skull base re‐RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.

Tumor cell viability in salvage neck dissections: Poor prognosis predicted by high postradiation nodal SUVmax, p16‐negativity, and low nodal shrinkage

19-12-2019 – Pascal Rüegg, Grégoire B. Morand, Ken Kudura, Niels J. Rupp, Martin W. Hüllner, Martina A. Broglie

Journal Article

Abstract
Background
After primary chemoradiation in advanced oropharyngeal, laryngeal, and/or hypopharyngeal cancer, nodal disease may require a salvage neck dissection. However, salvage neck dissection is associated with increased morbidity and may only be necessary in case of persistence of viable tumor cells, which can be difficult to confirm and virtually impossible to exclude by fine needle aspiration cytology. We, therefore, aimed to identify predictive factors for the persistence of viable tumor cells in lymph node metastases from head and neck squamous cell cancer after chemoradiation.
Methods
We performed a retrospective review of neck dissection specimens performed after primary (chemo‐)radiation for oropharyngeal, laryngeal, or hypopharyngeal squamous cell carcinoma. All patients were treated at University Hospital Zurich from 2007 to 2016.
Results
A total of 78 patients were included. Thirty‐eight patients (48.7%) had viable tumor cells in their neck dissection sample. High postradiation nodal maximum standardized uptake value (SUVmax), p16 negativity, and low nodal shrinkage were predictors of viable tumor cells in salvage neck dissections (Mann‐Whitney U/chi‐squared test, P < .001, P = .025, and P = .042, respectively). Patients with viable tumor cells showed a significantly worse locoregional recurrence‐free survival, distant metastasis‐free survival, and disease‐specific survival (log‐rank test, P < .001).
Conclusions
Viable tumor cells can be predicted by high residual metabolic activity in the lymph nodes, negative p16 status, and low nodal shrinkage. Viable tumor cells in neck dissection specimens are associated with a poor survival and provide important prognostic information.

Feasibility of single vocal cord irradiation as a treatment strategy for T1a glottic cancer

19-12-2019 – Seung Yeun Chung, Chang Geol Lee

Journal Article

Abstract
Background
Generally, radiotherapy for patients with early glottic cancer includes treatment of the whole larynx. This study was conducted to evaluate the treatment outcomes and toxicity in patients who received single vocal cord irradiation (SVCI) for T1a classification glottic cancer.
Methods
A total of 34 patients diagnosed with clinical T1a
N0M0 classification squamous cell carcinoma of the glottis who received radiotherapy to the single vocal cord were included for analysis.
Results
Median follow‐up period was 41.3 months (range, 6.4‐124.5 months). The 3‐year and 5‐year local control (LC) rates were both 96.8%. Grade 3 radiation dermatitis was observed as severe acute toxicity in two (6%) patients. No patients experienced any severe late toxicity events during follow‐up.
Conclusions
SVCI showed good LC, low acute and late toxicities, and reasonable voice recovery. SVCI may be considered a feasible treatment strategy for patients with T1a glottic cancer.

Exhaled breath analysis in the diagnosis of head and neck cancer

19-12-2019 – Antti A. Mäkitie, Alhadi Almangush, Omar Youssef, Markus Metsälä, Suvi Silén, Iain J. Nixon, Missak Haigentz, Juan P. Rodrigo, Nabil F. Saba, Vincent Vander Poorten, Alfio Ferlito

Journal Article, Review

Abstract
Head and neck cancer (HNC) comprises a heterogeneous group of upper aerodigestive tract malignant neoplasms, the most frequent of which is squamous cell carcinoma. HNC forms the eighth most common cancer type and the incidence is increasing. However, survival has improved only moderately during the past decades. Currently, early diagnosis remains the mainstay for improving treatment outcomes in this patient population. Unfortunately, screening methods to allow early detection of HNC are not yet established. Therefore, many cases are still diagnosed at advanced stage, compromising outcomes. Exhaled breath analysis (EBA) is a diagnostic tool that has been recently introduced for many cancers. Breath analysis is non‐invasive, cost‐effective, time‐saving, and can potentially be applied for cancer screening. Here, we provide a summary of the accumulated evidence on the feasibility of EBA in the diagnosis of HNC.

Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma

18-12-2019 – Yuki Saito, Alexander V. Favorov, Michael Forman, Shuling Ren, Akihiro Sakai, Takahito Fukusumi, Chao Liu, Sayed Sadat, Mizuo Ando, Guorong Xu, Zubair Khan, John Pang, Alex Valsamakis, Kathleen M. Fisch, Joseph A. Califano

Journal Article

Abstract
Background
We aimed to use genomic data for optimizing polymerase chain reaction (PCR) primer/probe sets for detection of human papillomavirus (HPV)‐16 in body fluids of patients with HPV‐related head and neck squamous cell carcinoma (HPV‐HNSCC).
Methods
We used genomic HPV‐HNSCC sequencing data from a single institutional and a TCGA cohort. Optimized primer/probe sets were designed and tested for analytical performance in Ca
Ski HPV‐16 genome and confirmed in salivary rinse samples from patients with HPV‐HNSCC.
Results
The highest read density was observed between E5 and L2 regions. The E1 region contained a region that was universally present. Among candidate PCR primer/probe sets created, six reliably detected 30 HPV‐16 copy number. In a CLIA certified laboratory setting, the combination of two novel primer/probe with E7 sets improved performance in salivary rinse samples with a sensitivity of 96% and specificity of 100%.
Conclusions
PCR‐based detection of HPV‐16 DNA in HPV‐HNSCC can be improved using rational genomic design.

Proton therapy for head and neck paragangliomas: A single institutional experience

18-12-2019 – Kylie H. Kang, Emily S. Lebow, Andrzej Niemierko, Marc R. Bussière, Nicholas A. Dewyer, Jillian Daly, Michael J. McKenna, Daniel J. Lee, Jay S. Loeffler, Paul M. Busse, Helen A. Shih

Journal Article

Abstract
Background
Although slow growing, head and neck paragangliomas (HNPG) can cause significant morbidity. We evaluated the efficacy of proton therapy in the management of HNPG.
Methods
Retrospective review of an institutional proton therapy experience of treating patients between 1997 and 2016; 37 patients and 40 tumors were included.
Results
Proton therapy was delivered to a median of 50.4 Gy(RBE) (range: 45‐68). Having a genetic/family predisposition for HNPG was associated with multifocal tumors (P = .02) and younger diagnosis age (P = .02). Twenty‐six (70%) patients had symptom improvement posttreatment, and 65% of treated tumors showed ≥20% volumetric shrinkage. The 5‐year recurrence‐free and overall survival rates were both 97%. Grade 2 to grade 3 toxicities (54%) included subjective hearing impairment (19%), middle ear inflammation (14%), and dry mouth (8%). There were no grade 4‐5 toxicities.
Conclusions
Patients with HNPGs can be effectively and safely treated with proton therapy with excellent tumor control, successful volumetric tumor reduction, and symptomatic improvement.

Survival advantage of chemoradiotherapy in anaplastic thyroid carcinoma: Propensity score matched analysis with multiple subgroups

16-12-2019 – Sibo Tian, Jeffrey M. Switchenko, Teng Fei, Robert H. Press, Mustafa Abugideiri, Nabil F. Saba, Taofeek K. Owonikoko, Amy Y. Chen, Jonathan J. Beitler, Walter J. Curran, Theresa W. Gillespie, Kristin A. Higgins

Journal Article

Abstract
Background
We compared overall survival (OS) between radiation therapy (RT) and chemoradiotherapy (CRT) in patients with anaplastic thyroid carcinoma (ATC) using a large database.
Methods
The National Cancer Data Base was queried for ATC patients diagnosed between 2004 and 2013 who received RT or CRT. Groups were balanced by propensity score matching (PSM) on nine relevant variables. OS was also examined in five paired subgroups given known patient heterogeneity.
Results
Of 858 total patients, 575 received CRT and 283 received RT. CRT was associated with decreased risk of death (hazard ratio HR 0.66, P < .001), 1‐year OS 25.5% vs 14.3%. A survival advantage to CRT was seen using PSM cohorts (HR 0.75, P = .006). Those receiving definitive surgery saw the greatest benefit to CRT over RT (HR 0.65, P = .009), 1‐year OS 39.6% vs 20.4%.
Conclusions
CRT is associated with decreased risk of death in ATC; the magnitude of CRT vs RT benefit varied by subgroup.

Association between pioglitazone use and head and neck cancer: Population‐based case‐control study

13-12-2019 – Tzong‐Hann Yang, Sudha Xirasagar, Yen‐Fu Cheng, Chuan‐Song Wu, Yi‐Wei Kao, Ben‐Chang Shia, Herng‐Ching Lin

Journal Article

Abstract
Background
This study aimed to evaluate the association between pioglitazone use and the occurrence of head and neck cancer.
Methods
Data for this case‐control study were retrieved from the Taiwan National Health Insurance Research Database. A total of 21 464 diabetic patients newly diagnosed with head and neck cancers were identified. We used propensity score matching to select 64 392 comparison patients (3:1 ratio). Multiple logistic regression modeling was used to examine the association of head and neck cancer with pioglitazone use in the 5 years preceding the cancer diagnosis.
Results
Bivariate analysis showed a significant difference in the prevalence of prior using pioglitazone between cases and controls (19.3% vs 18.5%, P < .001) was observed. Multiple regression analysis showed adjusted odds of pioglitazone use of 1.06 (95% CI: 1.02‐1.10) among cases relative to controls.
Conclusions
Prior pioglitazone use was associated with oral cavity cancer.

Onset of hypothyroidism after total laryngectomy: Effects of thyroid gland surgery and preoperative and postoperative radiotherapy

13-12-2019 – Robert E. Plaat, Boukje A. C. Dijk, Anneke C. Muller Kobold, Roel J. H. M. Steenbakkers, Thera P. Links, Bernard F. A. M. Laan, Boudewijn E. C. Plaat

Journal Article

Abstract
Background
To determine time of onset and risk of hypothyroidism after total laryngectomy (TL) with and without (hemi)thyroidectomy in relation to treatment regimen, that is, preoperative radiotherapy (RT‐TL), postoperative radiotherapy (TL‐RT), and postoperative re‐irradiation (RT‐TL‐RT).
Methods
Retrospective review of 128 patients treated by RT‐TL (51 patients), TL‐RT (55 patients), and RT‐TL‐RT (22 patients). Risk of hypothyroidism was determined by multivariable Cox regression analysis and euthyroid survival was calculated using Kaplan‐Meier method.
Results
Hypothyroidism developed in 69 (54%) patients. The median onset of hypothyroidism was later (P < .01) and the risk of hypothyroidism was lower (hazard ratio 0.49; P = .014) in the TL‐RT group compared to both other treatment regimens. Euthyroid survival did not differ between the treatment regimens. Two years euthyroid survival was 24% with and 61% without (hemi)thyroidectomy (P < .001).
Conclusions
Patients treated with TL‐RT have later onset of hypothyroidism. Higher risk for hypothyroidism is associated with salvage TL after radiotherapy and (hemi)thyroidectomy.

Variations in concerns reported on the patient concerns inventory in patients with head and neck cancer from different health settings across the world

13-12-2019 – Simon N. Rogers, Alvaro Alvear, Alexandre Anesi, Emmanuel Babin, Ali Balik, Martin Batstone, Phillipp Brockmeyer, Claudia Celedon Carrasco, Chih‐Yen Chien, Magdalena Chirila, Kanchan P. Dholam, Jennifer G. Doss, Caterina Finizia, Wan M. Nabilah Ghani, Sandeep V. Gurav, Kathreena Kadir, Mateusz Kolator, Roberto Lima, Yu‐Tsai Lin, Simon Nhongo, Meltem Ozdemir‐Karatas, Kadriye Peker, Zoran Pesic, Pierre Ransy, Izabella Santos, Henning Schliephake, Ketan Shah, Fernanda Souza, Geethu Sunil, Krishnakumar Thankappan, Ylva Tiblom Ehrsson, Cristina Tiple, Lisa Tuomi, Sara Valerini, Pablo Vasquez Lara, Tomasz Zatoński, Derek Lowe

Journal Article

Abstract
Background
The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow‐up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL).
Methods
Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias.
Results
There were 2136 patients with a median total number of PCI items selected of 5 (2‐10). “Fear of the cancer returning” (39%) and “dry mouth” (37%) were most common. Twenty‐five percent (524) reported less than good QOL.
Conclusion
There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case‐mix variables. There was a strong progressive association between the number of PCI items and QOL.

Management of orbital complications in palatomaxillary reconstruction: A review of preemptive and corrective measures

13-12-2019 – Martha J. Griffin, John R. Sims, Sarah L. Spaulding, Fred M. Baik, Ebrahim Elahi, Mark L. Urken

Journal Article, Review

Abstract
Background
Reconstruction of orbit‐sparing palatomaxillary defects requires consideration of globe dystopia, orbital volume, eyelid position and function, and the nasolacrimal system to preserve and optimize vision, globe protection, and appearance. We describe the fundamentals of orbital and eyelid anatomy, common orbital complications related to palatomaxillary reconstruction, and preemptive and corrective surgical techniques to be utilized during and after globe‐sparing palatomaxillary reconstruction.
Methods
We present a review of the literature supplemented by clinical case examples.
Results
We advocate for the use of preemptive and corrective techniques to ensure optimal aesthetic and functional outcomes for patients with orbital defects.
Conclusions
Recognition and anticipation of problems in patients undergoing midface ablative and reconstructive procedures are vital to the implementation of corrective measures. Incision choice, orbital volume restoration, appropriate orbital floor reconstruction, and permanent or temporary lower eyelid suspension during the primary surgery can all significantly impact the development of long‐term orbital complications.

Pharyngeal swallowing mechanics associated with upper esophageal sphincter pressure wave

05-12-2019 – “Nelson H. May, Kate W. Davidson, William G. Pearson, Ashli K. ORourke”

Journal Article

Abstract
Background
Opening of the upper esophageal sphincter (UES) is a critical element of swallowing. Understanding the functional pharyngeal anatomy during UES opening would be clinically useful for dysphagia evaluation and treatment.
Methods
Simultaneous high‐resolution pharyngeal manometry and videofluoroscopy (VFS) videos for 18 nondysphagic subjects were evaluated. UES pressure readings were segmented into six pressure phases, including a poorly understood pre‐relaxation contraction. Anatomic landmarks were tracked in VFS imaging and evaluated morphometrically to determine the movement of key swallowing structures within each UES pressure phase.
Results
There were significant differences in pharyngeal mechanics by UES pressure stage (range of D‐values = 1.7‐2.2, P < .0001). The soft palate maximally elevates during the pre‐relaxation contraction of the UES. Early during UES relaxation, the hyolaryngeal complex and pharyngeal structures maximally elevate and pharyngeal structures constrict around the bolus.
Conclusion
The mechanics underlying the UES pressure wave suggest generation of a sealed pharyngeal cavity, possibly integral to pharyngeal pressure generation and bolus propulsion.

Potentially malignant disorders of the oral cavity and oral dysplasia: A systematic review and meta‐analysis of malignant transformation rate by subtype

05-12-2019 – Oreste Iocca, Thomas P. Sollecito, Faizan Alawi, Gregory S. Weinstein, Jason G. Newman, Armando De Virgilio, Pasquale Di Maio, Giuseppe Spriano, Simón Pardiñas López, Rabie M. Shanti

Journal Article, Review

Abstract
Importance
Potentially malignant disorders of the oral cavity (OPMD) are a heterogeneous group of lesions associated with a variable risk of malignant transformation (MT) to invasive cancer. Leukoplakia (LE), lichen planus (LP), oral lichenoid lesions (OLL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and proliferative verrucous leukoplakia (PVL) are among the most common of these lesions. Oral dysplasia is a mucosal area characterized by cellular and architectural derangement, which may be associated with OPMDs or not.
Objective
To define the MT rate of OPMDs and the risk of development into cancer of mild vs moderate/severe oral dysplasia. This in order to implement adequate follow‐up strategies and treatment decisions.
Study design
We performed a systematic review and meta‐analysis on studies reporting the MT rates of OPMDs and oral dysplasia. Ninety‐two studies were included for the analysis. Cumulative rates were reported for OPMDs overall and as a subgroup, a comparison was made of mild vs moderate/severe dysplasia. Meta‐regression on OPMD and year of publication was also performed.
Main outcome and measures
Overall MT rates of OPMDs and odds ratio of MT of mild vs moderate/severe dysplasia.
Results
Overall MT rate across all OPMD groups was 7.9% (99% confidence interval CI 4.9%‐11.5%). MT rates of the specific OPMD subgroups were as follows: LP 1.4% (99% CI 0.9%‐1.9%), LE 9.5 (5.9%‐14.00%), OLL 3.8% (99% CI 1.6%‐7.00%), OSF 5.2% (99% CI 2.9%‐8.00%), OE 33.1% (99% CI 13.6%‐56.1%), and PVL 49.5% (99% CI 26.7%‐72.4%). Regarding the dysplasia grades comparison, the meta‐analysis showed that moderate/severe dysplasia is meaningfully associated to a much greater risk of MT compared to mild dysplasia with an odds ratio of 2.4 (95% CI 1.5‐3.8) Correction added on 27 December 2019, after first online publication: CI updated from 99% to 95%.. Heterogeneity was not significant. Annual MT rates were approximated based on the average follow‐up as reported in the various subgroups. Lichen planus had an annual MT of 0.28%, OLL of 0.57%, leukoplakia of 1.56%, PVL of 9.3%, and OSF of 0.98%. Mild dysplasia had an annual MT of 1.7%, while severe dysplasia of 3.57%. Meta‐regression showed a significant negative correlation of PVL MT rate and year of the study (P value <.001).
Conclusions and relevance
OPMDs and oral dysplasia are relatively common conditions that general practitioners, head and neck, and oral medicine specialists, face in their everyday practice. Our analysis confirms the significant risk of MT of these lesions, although variable among the subgroups. Moderate/severe dysplasia bears a much higher risk of cancer evolution than mild dysplasia. It is important to raise public health awareness on the MT rates of these conditions, at the same time efficacious communication with the patient is of utmost importance. This, coupled with strict follow‐up measures and optimal treatment strategies, would help in reducing the transformation of these oral conditions into invasive cancer.

Scoring system for selective tracheostomy in head and neck surgery with free flap reconstruction

04-12-2019 – Tian‐yi Cai, Wen‐bo Zhang, Yao Yu, Yang Wang, Chi Mao, Chuan‐bin Guo, Guang‐yan Yu, Xin Peng

Journal Article

Abstract
Background
Selective tracheostomy is an effective but invasive airway management method for patients undergoing head and neck free flap reconstruction. Studies have shown that not all patients need tracheostomy. Several systems evaluating the need for tracheostomy have been proposed, but none is used clinically.
Methods
A total of 533 cases underwent head and neck free flap reconstruction at Peking University School of Stomatology were reviewed for system development. Another 131 cases undergone the same surgery were included for system verification. Patients demographic and surgical‐related information were analyzed.
Result
A total of 321 cases in the development cohort and 68 cases in the system cohort underwent tracheostomy. The score was estimated: score = ∑(|log2OR|). Patients scoring >3 required tracheostomy, those scoring <2 should avoid tracheostomy, and those scoring 2 or 3 need further evaluation.
Conclusion
This scoring system can help determine the need for selective tracheostomy in patients undergoing head and neck free flap reconstruction.

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma

04-12-2019 – Chengrun Du, Pierre Blanchard, Caroline Even, Angela Boros, Philippe Gorphe, Ingrid Breuskin, Neus Baste‐Rotllan, France Nguyen, Amandine Ruffier, François Bidault, Camélia Billard, François Janot, Haitham Mirghani, Stephane Temam, Yungan Tao

Journal Article

Abstract
Background
The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors.
Methods
A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported.
Results
The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non‐responders in terms of 5‐year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders.
Conclusions
This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.

Long‐term opioid use in curative‐intent radiotherapy: One‐Year outcomes in head/neck cancer patients

30-11-2019 – Leif‐Erik D. Schumacher, Zoukaa B. Sargi, Melissa Masforroll, Deukwoo Kwon, Wei Zhao, Maria A. Rueda‐Lara, Laura M. Freedman, Nagy Elsayyad, Stuart E. Samuels, Matthew C. Abramowitz, Michael A. Samuels

Journal Article

Abstract
Background
No study has determined the incidence of long‐term opioid use, or risk factors for long‐term use, ≥1 year after radiotherapy.
Methods
Medical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1‐year after curative‐intent radiotherapy. Numerous potential risk factors were assessed and the physicians documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain.
Results
Of note, 20 of 276 patients continued using opioids long‐term. High maximum opioid dose and the use of opioids and/or psychotropics/non‐opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications.
Conclusion
Of note, 7.2% of patients developed long‐term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non‐opioid analgesics. Physicians cited medical indications as the primary reason for continued use.

Lymphatic mapping with SPECT‐CT for evaluation of contralateral drainage in lateralized oropharyngeal cancers using an awake injection technique

28-11-2019 – Carissa M. Thomas, Mohemmed N. Khan, Ravi Mohan, Aaron Hendler, Ali Hosni, Douglas B. Chepeha, David P. Goldstein, Richard M Cooper, John R. Almeida

Journal Article

Abstract
Background
Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is currently based on clinical risk factors. We propose lymphatic mapping with single photon emission computed tomography (SPECT‐CT) for tumor‐specific delineation of lymphatic drainage to guide treatment.
Methods
Retrospective review of lymphatic drainage patterns in c
T1‐2 OPSCC and contralateral c
N0 neck with a nonoperative, awake injection of 99 m‐Tc sulfur colloid and SPECT‐CT.
Results
Ten patients were reviewed. Primary sites included tonsil (n = 8, 80%) and tongue base (n = 2, 20%). All patients tolerated awake injections with no complications. Nine patients (90%) demonstrated satisfactory migration of radiotracer to neck node(s) with seven (78%) to the ipsilateral lateral neck, one (11%) to the ipsilateral lateral neck and retropharynx, and one (11%) to bilateral lateral neck nodes.
Conclusions
Characterization of lymphatic drainage in OPSCC is feasible using a nonoperative injection technique and SPECT‐CT. Drainage to the contralateral neck is rare, warranting further study to tailor treatment appropriately.

Potential pitfalls in incorporating plasma Epstein‐Barr virus DNA in the management of nasopharyngeal carcinoma

28-11-2019 – Edwin C. Y. Wong, Jessica L. C. Hung, Wai T. Ng

Journal Article

Abstract
Background
This study identifies potential pitfalls in incorporating plasma Epstein‐Barr virus (EBV) DNA into the management of nasopharyngeal carcinoma (NPC).
Methods
A total of 208 NPC patients without distant metastasis who received radical treatment and had measurements of EBV DNA at baseline, 8 weeks and 26 weeks postradiotherapy were analyzed. Prognostic and predictive values at each time‐point were compared.
Results
Risk stratification by pretreatment level failed to identify a poor prognostic group. Detectable EBV DNA at 8 weeks and 26 weeks postradiotherapy were both associated with significantly poorer 5‐year disease‐free survival (HR 0.30, P < .001 and HR 0.03, P < .001, respectively) and overall survival (HR 0.27, P = .009 and HR 0.03, P < .001, respectively). Eighty percentage had detectable EBV DNA at recurrence (53.3% for local only, 100% for regional only, and 100% for distant failure).
Conclusions
Posttreatment EBV DNA, particularly at 26 weeks post‐radiotherapy, has high prognostic and predictive values. Surveillance endoscopy/imaging are recommended for the detection of local recurrence.

Prophylactic arterial ligation following transoral robotic surgery: A systematic review and meta‐analysis

28-11-2019 – Craig A. Bollig, David R. Gilley, Jumah Ahmad, Jeffrey B. Jorgensen

Journal Article, Review

Abstract
Prophylactic arterial ligation has been proposed to reduce the severity of postoperative hemorrhage following transoral robotic surgery (TORS). Previous studies have shown a trend toward a reduction in major and severe bleeding. Search strategies were implemented in multiple databases and completed in August 2018. Inclusion and exclusion criteria were designed to capture studies examining adults undergoing TORS for oropharyngeal cancer. Four retrospective studies were selected appropriate for analysis by two reviewers who independently extracted data. PRISMA guidelines were followed. A random‐effects model was used for meta‐analysis. Meta‐analysis of 619 patients in four retrospective reviews showed that the pooled RR of major and severe bleeding events was significantly lower in prophylactically ligated patients (RR, 0.28; 95% CI, 0.08‐0.92; I2 = 0). Prophylactic arterial ligation of external carotid artery branches is associated with a decreased risk of major and severe bleeding events, although confounding factors remain incompletely analyzed.

Alcohol‐related head and neck cancer: Summary of the literature

27-11-2019 – Allison Marziliano, Sewit Teckie, Michael A. Diefenbach

Journal Article, Review

Abstract
Alcohol drinking is a risk factor for the development of head‐and‐neck malignancies, including oral, pharyngeal, and laryngeal cancers, and coupled with tobacco use, accounts for 75% of oral cancers. We summarized the literature on alcohol‐related head and neck cancer (HNC) and identified gaps that represent areas for future investigation. Research indicates that alcohol consumption has not only been linked to the development of primary HNCs, but also to secondary cancers with continued alcohol intake, cancer recurrences, and other poor health outcomes. Given this evidence, several organizations have called for reduction or avoidance of alcohol, particularly in HNC survivors. Despite these strong recommendations, evidence suggests that HNC survivors continue to use alcohol. There is a need to forge collaborations among clinicians, researchers, and social workers, to address this problem of alcohol consumption in the growing population of HNC survivors.

Anatomical subsite modifies survival in oropharyngeal squamous cell carcinoma: National Cancer Database study

27-11-2019 – Tristan Tham, Seungjun Ahn, Douglas Frank, Dennis Kraus, Peter Costantino

Journal Article

Abstract
Background
Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (n
TRA). The prognostic differences between these sites are unclear. This study investigated this question using the National Cancer Database (NCDB), controlling for other confounders including human papillomavirus (HPV) status.
Methods
This NCDB study was conducted by stratifying the HPV‐positive oropharyngeal cancer cohort into two primary groups, TRA and n
TRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression.
Results
A total of 23 297 patients were included in this study. In the multivariable cox regression analysis, OPSCC subsite was found to be an independent prognostic factor for survival (TRA vs n
TRA HR: 0.76, 95% CI: 0.67‐0.86, P < .0001).
Conclusion
In this large cohort, OPSCC subsite was found to be an independent prognostic factor for survival.

Radiation treatment of soft palate squamous cell carcinoma

27-11-2019 – Cooper T. Rapp, Bhishamjit S. Chera, Christopher G. Morris, Robert J. Amdur, Jessica M. Kirwan, William M. Mendenhall

Journal Article

Abstract
Background
To report our institutions experience treating soft palate squamous cell carcinoma with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease.
Methods
We analyzed 159 patients treated curatively between 1963 and 2016. Median follow‐up was 4 years.
Results
The 5‐year local control rates were T1, 90%; T2, 90%; T3, 70%; and T4, 59%. The 5‐year cause‐specific survival (CSS) rate was nearly identical for patients with stage I‐III disease (88%, 86%, and 88%, respectively) compared to stage IVA/B (58%). Five‐year overall survival was similar between patients with stage I‐III disease (50%, 57%, and 54%, respectively) and approximately double that of patients with stage IVA/B disease (26%). Thirteen patients (8%) had severe complications related to radiotherapy.
Conclusions
The likelihood of cure after definitive radiotherapy is relatively high in patients with stage I‐III disease with soft palate carcinoma. Patients with stage IVA/B disease have a lower cure rate but with a 5‐year CSS exceeding 50%.

Complications of tissue expansion in the head and neck

27-11-2019 – Jayson L. Azzi, Chloe Thabet, Alain J. Azzi, Mirko S. Gilardino

Journal Article, Review

Abstract
Background
The authors aim to present a comprehensive review detailing the present state of evidence with regard to complications following tissue expansion in the head and neck.
Methods
A systematic literature search was conducted to identify all studies reporting complications of tissue expansion in the head and neck between 2000 and 2019. Subgroup comparisons based on expander locations and planes were conducted.
Results
A total of 7058 patients were included. Tissue expansion was associated with an overall complication rate of 8.73% (616/7058). The most common complications were extrusion (207/7009; 3.0%) and hematoma (200/7009; 2.9%). Overall complications were highest in the scalp (65/238; 27.3%) and lowest in the mastoid (347/5688; 6.1%). Complications were more common with expansion in the non‐subcutaneous plane (63/590; 10.7%).
Conclusion
In the absence of large clinical trials, systematic reviews such as these can help inform clinical guidelines and provide practitioners with an evidence‐based reference to improve informed consent.

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

27-11-2019 – Nader Sadeghi, Sarah Khalife, Marco A. Mascarella, Agnihotram V. Ramanakumar, Keith Richardson, Arjun S. Joshi, Nathaniel Bouganim, Reza Taheri, Andrew Fuson, Robert Siegel

Journal Article

Abstract
Background
A paradigm shift has led to de‐escalation trials for the treatment of HPV‐positive oropharynx cancer (OPC). The objective of this study was to assess the ability of tumor volume reduction on imaging to predict pathological response to neoadjuvant chemotherapy in patients with HPV‐positive OPC.
Methods
A prospective observational study of 54 patients with HPV‐positive OPC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. Patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); prechemotherapy and postchemotherapy imaging were obtained. Receiver operating characteristic curves and logistic regression analyses were used.
Results
The complete pathologic response (p
CR) rate at primary and nodal sites were 72% and 57%, respectively. Tumor volume reduction of ≥90% following induction chemotherapy predicted p
CR of the primary tumor.
Conclusions
Neoadjuvant chemotherapy followed by definitive transoral surgery is a new paradigm worthy of further investigation and MRI is a reliable modality to assess preoperative response.

Reply to “Possible risk of iatrogenic lymphedema after harvest of posterior tibial artery perforator flap”

26-11-2019 – Jun Liu, Di Deng, Fei Chen

Letter