Oral Oncology

Oral Oncology

Two for the price of one: Prevalence, demographics and treatment implications of multiple HPV mediated Head and Neck Cancers

26-11-2019 – William Strober, Sachie Shishido, Burton Wood, James S. Lewis, Krystle Kuhs, Robert L. Ferris, Daniel L. Faden

Journal Article

Objectives

HPV mediated head and neck squamous cell carcinoma (HPVm
HNSCC) is increasing in prevalence in the United States, as are reports of patients with multiple HPVm
HNSCCs. The prevalence, demographics, and treatment implications of this emerging clinical entity are poorly understood.

Materials and methods

We performed a multitiered assessment of patients with multiple HPVm
HNSCC including: 1. systematic review of the literature, 2. query of the 2017 Surveillance, Epidemiology and End Results (SEER) database and 3. institutional level reporting at two high volume academic centers.

Results

Systematic literature review: 13 articles met inclusion criteria (48 patients with multiple HPVm
HNSCC). Pooled prevalence rate of multiple HPVm
HNSCC was 2.64%. SEER database: 60(0.95%) patients with HPVm
HNSCC had two tumors. Patients with multiple HPVm
HNSCC were more likely to be younger and present with a lower T and N stage (p < 0.025 for all). The second identified tumor was more likely to be contralateral, found synchronously, of smaller size, and to occur in the tonsil (p < 0.05 for all). Institutional reporting: 17(1.69%) patients with HPVm
HNSCC had two primary tumors. Similar to the SEER database, patients with multiple HPVm
HNSCC were more likely to present with a low T stage and tonsil location (p < 0.007 for both).

Conclusion

Multiple HPVm
HNSCCs occur in a subset of HPVm
HNSCC cases with distinct characteristics. Thorough interrogation of all oropharyngeal subsites should be performed as part of the initial workup for HPVm
HNSCC, with consideration given to contralateral tonsillectomy at the time of surgical resection for HPV mediated tonsil cancers due to the prevalence of contralateral tonsil primaries.

Management of the neck in oral cancers

04-12-2019 – Gouri Pantvaidya, Karthik Rao, Anil DCruz

Journal Article

Oral cavity cancers are treated by surgery with or without adjuvant therapy. Being the most important prognostic factor, neck node management is an important aspect of treating oral cancers. There are numerous areas of debate in the management of the node-negative and node-positive neck. In an attempt to answer these questions, a large volume of literature has been generated over the last few decades. This review article describes the current evidence and approach considerations for the management of cervical nodes in patients with oral cavity cancers.

Establishment and validation of a nomogram for predicting the benefit of concurrent chemotherapy in stage II nasopharyngeal carcinoma: A study based on a phase III randomized clinical trial with 10-year follow-up

04-12-2019 – Xue-Song Sun, Xiao-Yun Li, Bei-Bei Xiao, Sai-Lan Liu, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai

Journal Article

Background and Purpose

Our previous phase III randomized trial demonstrated that the addition of concurrent chemotherapy to radiotherapy (RT) could improve survival in stage II nasopharyngeal carcinoma (NPC). Based on the study, we sought to develop a nomogram for predicting the 5-year and 10-year survival of patients with stage II NPC and estimating the benefit of concurrent chemoradiotherapy (CCRT) for individual patients.

Materials and methods

Data of 199 enrolled patients from the original trial was analyzed to build a nomogram. Overall survival (OS) was the primary endpoint. The discrimination and calibration capacities were evaluated using Harrell Concordance Index (C-index) and calibration curves, respectively. Internal validation of the nomogram was performed by a separate cohort of 306 patients from the same cancer center.

Result

In training cohort, patients in CCRT group achieved higher 5-year and 10-year OS compared with patients in RT group. Three independent prognostic factors, which were age, N stage and treatment method from multivariable analysis were extracted to enter the nomogram. T stage was also included due to its importance in clinical decisions. The Harrell C-index of the nomogram in training and validation cohort was 0.748 and 0.653 respectively. The calibration curves showed an acceptable agreement between prediction and observed probability.

Conclusion

We developed and validated a nomogram to predict the 5-year and 10-year OS in stage II NPC patients. The nomogram could serve as a pragmatic tool in clinical decisions to estimate the individual risk of stage II patients and identify those who could benefit from chemotherapy.

Classification of three prognostically different groups of head and neck cancer patients based on their metabolic response to induction chemotherapy (IC-1)

02-12-2019 – Sabine Semrau, Daniela Schmidt, Markus Hecht, Marlen Haderlein, Christian Kitzsteiner, Sarina Müller, Maximilian Traxdorf, Abbas Agaimy, Heinrich Iro, Torsten Kuwert, Rainer Fietkau

Journal Article

Objectives

There exist no uniform decision criteria for conservative organ preservation treatments in head and neck cancer patients. Even with 18F-FDG-PET/CT after induction chemotherapy patient selection is challenging. This study correlated metabolic tumor response with treatment types and recurrence patterns.

Materials and methods

Decrease in SUVmax in 18F-FDG-PET/CT was measured 21–28 days after IC-1 in 102 patients and correlated to cancer-specific endpoints.

Results

Residual SUVmax (res
SUVmax) values were uniformly distributed across five cut-off levels (0–0.2 vs. >0.2–0.4 vs. >0.4–0.6 vs. >0.6–0.8 vs. >0.8) containing 20%, 25% 25%, 15% and 15% of patients. Patients were stratified into three response categories according to residual SUVmax (Group A: 0–0.4 = high response Group B: >0.4–0.8 = moderate response, Group C > 0.8 = non-response), 5-year local control rates were 90.5% (Group A) vs. 78.9% (Group B; univariate p = 0.07, multivariate: HR: 3.6, p = 0.03) vs. 49.4% (Group C vs. B; univariate p = 0.04, multivariate: HR 5.5, p < 0.01). After IC-1, Group A received chemoradiotherapy (CRT) only. Group B received surgery plus either (chemo)radiotherapy (B_S + RT/CRT) or chemoradiotherapy (B_CRT), yielding local control rates of 100% and 74.2% (p = 0.11). Group C received surgery plus CRT or CRT alone; both achieved equally poor local control (p = 0.71). Group C had significantly worse distant metastasis-free survival and overall survival than Groups A and B (p < 0.05).

Conclusion

Metabolic response after IC-1 differentiates HNC patients into three subgroups predicting local tumor control. Non-response was associated with a poor outcome.

“Assessment of fibula flap with flexor hallucis longuss effect on head & neck tumor patients quality of life and function of donor site”

01-12-2019 – Youkang Ni, Xuedi Zhang, Zhiqiang Zhang, Weidi Liang, Lina Zhao, Zijia Li, Siqi Li, Ping Lu, Zhongfei Xu, Wei Dai, Weiyi Duan, Xuexin Tan, Changfu Sun, Fayu Liu

Journal Article

Objective

Free fibular flaps (FFFs) have been widely used in mandibular reconstruction. It is still unclear whether retaining flexor hallucis longus (FHL) is needed for flaps. This study introduces a comparison in quality of life and donor-site function between those who have and havent harvested FHL with FFF.

Methods

Patients with FFFs were single-blind-randomly assigned into the FHL group or n
FHL group. Patients were followed up preoperatively and 1, 3 and 6 months postoperatively via subjective evaluations (SF-36/AOFAS) and objective evaluation s(muscle strength and range of motion). Patients hospitalization and intraoperative information, donor site morbidity were recorded.

Results

Each group had 15 patients. The flap harvesting time in FHL group was shorter significantly than n
FHL group (125.9 ± 24.8 min vs 146.7 ± 29.9 min, P = 0.048). There were no significant differences in hospitalization information such as operation time, hospitalization days and cost. Donor site morbidities at 1, 3 and 6 months postoperatively showed no significant differences except for the presence of claw toes (n
FHL group > FHL group, 40% vs 0, P = 0.017; 53.3% vs 6.7%, P = 0.014; 60.0% vs 13.3%, P = 0.021). There were no significant differences in SF-36 and AOFAS scores. There were no significant differences in muscle strength and range of motion.

Conclusion

Excision of the FHL lowered the flap harvesting time. It did not increase donor site morbidity. The impacts on patients quality of life and foot function were the same. The surgeons can use the FHL without considering the influence on patients if not retaining the FHL.

Time and cost-analysis of virtual surgical planning for head and neck reconstruction: A matched pair analysis

04-12-2019 – Francesco Mazzola, Fiona Smithers, Kai Cheng, Payal Mukherjee, Tsu-Hui (Hubert) Low, Sydney Chng, Carsten E. Palme, Jonathan R. Clark

Journal Article

Objectives

Virtual surgical planning (VSP) uses patient-specific modelling of the facial skeleton to provide a tailored surgical plan which may increase accuracy and reduce operating time. The aim of this study was to perform a time and cost-analysis comparing patients treated with and without VSP-technology.

Material and methods

A retrospective analysis of 138 patients undergoing microvascular free flap mandible (76.8%) or maxillary (23.2%) reconstruction between 2010 and 2018 was performed. The cohort was divided into two groups according to reconstruction-approach: non-VSP and proprietary-VSP (P-VSP). Cost-analysis was performed comparing non-VSP and P-VSP by matching patients according to site, bone flap, indication, complexity and age.

Results

Fibula, scapula and iliac crest free flaps were used in 92 patients (66.7%), 33 patients (23.9%) and 13 patients (9.4%), respectively. Eight patients (5.8%) required revision of the microvascular anastomosis, of which four flaps were salvaged giving a 2.9% flap failure rate. P-VSP was associated with shorter median length of stay (LOS) (10.0 vs 13.0 days, p = 0.009), lower mean procedure time (507.38 vs 561.75 min, p = 0.042), and similar median total cost ($34939.00 vs $34653.00, p = 0.938), despite higher complexity (2.0 vs 1.0, p = 0.09). In the matched-series, P-VSP was associated with a similar median LOS (10.5 vs 11 days), lower mean procedure time (497 vs 555 min, p = 0.231), lower mean total cost ($35,493 v $37,345) but higher median total cost ($35504.50 vs $32391.50, p = 0.607), although not statistically different.

Conclusion

VSP-technology represents a helpful surgical tool for complex reconstructions, without adversely impacting on the overall-cost of treatment.

Homologous recombination enhances radioresistance in hypopharyngeal cancer cell line by targeting DNA damage response

23-11-2019 – Chuan Liu, Kui Liao, Neil Gross, Zhihai Wang, Guojun Li, Wenqi Zuo, Shixun Zhong, Zixin Zhang, Hua Zhang, Jianming Yang, Guohua Hu

Journal Article

Background

Radiotherapy is a central treatment option for hypopharyngeal squamous cell carcinoma, but the prognoses of patients treated with radiotherapy only are not satisfactory due to radioresistance. The underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of radioresistance are currently unavailable.

Methods

In this study, we first established a specifically radioresistant Fa
Du cell line by repeated exposure to ionizing radiation with a total dose of 60 Gy (Fa
Du-RR). The validation of Fa
Du-RR cells was performed by clonogenic cell survival assay and cell proliferation assay. Microarrays and bioinformatics were analyzed to determine the differentially expressed m
RNAs and their functions. DNA-repair capabilities were tested by cell cycle analysis and comet assay. The expressions of four key proteins in homologous recombination pathways, including BRCA1, BRCA2, RPA1, and Rad51, were detected both in Fa
Du-RR cells and radioresistant xenograft.

Results

We established the specifically radioresistant Fa
Du cell line. Through microarrays and bioinformatics, homologous recombination pathways were suggested to play important roles in radioresistant mechanisms. High expression levels of key proteins in homologous recombination pathways were then detected both in Fa
Du-RR cells and radioresistant xenograft. Silencing RPA1 could reduce the radioresistance of Fa
Du-RR cells.

Conclusion

Our results provided strong evidence that homologous recombination enhances the radioresistance in hypopharyngeal carcinoma. Proteins in homologous recombination pathways may be potential biomarkers to predict hypopharyngeal carcinoma response to radiotherapy, establishing a basis for their utility in clinical practice.

Prognostic efficacy of extensive invasion of primary tumor volume for T3-4 nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

24-11-2019 – Fen Xue, Dan Ou, Xiaomin Ou, Xin Zhou, Chaosu Hu, Xiayun He

Journal Article

Objectives

This study aimed to explore the prognostic value of extensive invasion of primary tumor volume for local control in patients with T3-4 NPC receiving intensity-modulated radiotherapy (IMRT).

Materials and methods

Between January 2009 and December 2015, initial volume of GTV-P, the confined and extensive invasion part of GTV-P (GTV-C and GTV-E) were obtained from 159 prospectively enrolled non-metastatic T3-4 NPC patients. GTV-E included the tumor with infiltration of bony structures at skull base, cervical vertebra, paranasal sinuses or with intracranial extension. GTV-C was calculated by the subtraction of GTV-E from GTV-P. The effects of tumor volume levels on local control rate (LC) were evaluated by Kaplan-Meier method and multivariate analysis.

Results

GTV-P (P = 0.015) and GTV-E (P = 0.001) were significantly correlated with local failure, while GTV-C (P = 0.494) was not. Then optimal cut-off values of GTV-P (43 m
L) and GTV-E (22 m
L) were determined by receiver operating characteristic curve analysis. Patients with small (<22 m
L) GTV-E achieved better 5-year LC rate than those with large (≥22 m
L) GTV-E (96.3% vs.76.1%, P < 0.001), but no significant difference was found between patients with small (<43 m
L) and large (≥43 m
L) GTV-P (95.9% vs. 85.5%, P = 0.094). Multivariate analysis also demonstrated large (≥22 m
L) GTV-E to be an independent unfavorable prognostic factor for LC (hazard ratio HR, 3.805; 95% CI, 1.100–13.166; P = 0.035).

Conclusion

GTV-E is an independent prognostic factor for LC in T3-4 NPC and may further assist in the optimization of treatment strategies.

Patterns of failure and outcomes in cT4 Oral squamous cell carcinoma (OSCC) undergoing upfront surgery in comparison to Neo-Adjuvant Chemotherapy (NACT) followed by surgery: A Matched Pair analysis

19-11-2019 – Shivakumar Thiagarajan, Harsh Dhar, Atanu Bhattacharjee, Khuzema Saifuddin Fatehi, Snehal Bhupesh Shah, Devendra Chaukar, Deepa Nair, Anuja Deshmukh, Kumar Prabhash, Amit Joshi, Vijay Patil, Vanita Noronha, Sarbani Ghosh Laskar, Anil K.D. Cruz

Journal Article

Dental caries following radiotherapy for head and neck cancer: A systematic review

02-12-2019 – Ciaran Moore, Conor McLister, Christopher Cardwell, Ciaran ONeill, Michael Donnelly, Gerald McKenna

Journal Article, Review

Post-radiotherapy head and neck cancer patients are at increased risk of dental caries due to radiotherapy-induced salivary gland hypofunction and radiation-damage to tooth structure. Dental caries may cause pain and discomfort, and is likely to have a detrimental impact on patients’ quality of life. This systematic review appraised and synthesised best available evidence regarding the incidence and severity of post-radiotherapy dental caries in head and neck cancer patients. Six databases and two trial registries were searched from their inception to May 2019. A total of 22 papers met the inclusion criteria. The pooled percentage of patients that developed dental caries post-radiotherapy was 29% (n = 15 studies; 95% CI 21%, 39%; I2 = 88.0%). Excluding studies with longer than two years follow-up, the pooled percentage was 37% (n = 9 studies; 95% CI 25%, 51%; I2 = 88.6%). Meta-regression analysis revealed that studies with a higher mean/median radiotherapy dose exposure, had an increased incidence of dental caries (p = 0.02). Furthermore, studies with a higher proportion of patients treated with chemotherapy in addition to radiotherapy, had an increased incidence of dental caries (p = 0.02) after the exclusion of an outlier. It is important to be mindful of the high degree of observed heterogeneity and the inclusion of a large number of non-randomised studies. Data regarding the number of carious teeth, the number of carious tooth surfaces, and the number of carious lesions developed post-radiotherapy was unsuitable for meta-analysis. There is a need for well-designed research studies to improve understanding of dental caries-risk in post-radiotherapy head and neck cancer patients.

Locally advanced non-melanomatous skin cancer: Contemporary radiotherapeutic management

26-11-2019 – Lachlan McDowell, Sue S. Yom

Journal Article

Non-melanomatous skin cancers (NMSC), comprising both cutaneous squamous cell carcinomas (SCC) and basal cell carcinomas (BCC), are the most common malignancies in fair-skinned persons, frequently arising in the sun-exposed head and neck region. Simple surgical excision is usually curative in the majority of low-risk cases, when functional and cosmetic preservation is typically easily achieved. A number of factors portend a more aggressive course in localised lesions, including pathological features such as an involved surgical margin, moderate to poor differentiation, or perineural or lymphovascular invasion, and clinical features including immunosuppression and recurrent cancer status. Though high-level evidence is lacking, consensus guidelines consistently recommend adjuvant radiotherapy in high-risk NMSCs, most commonly in the setting of a positive margin or extensive perineural disease. In non-operative candidates, high-dose radiotherapy can provide long-term control and survival. In SCC, high risk lesions pose an increased risk of regional spread, and consideration should be given to elective nodal treatment, either with neck dissection or irradiation. Development of regional disease, often to the parotid or cervical nodes in the head and neck region, shifts the prognosis substantially and combined therapy consisting of surgery and radiotherapy is then recommended. Limited evidence supports the use of the emerging technologies of protons, heavy particles or stereotactic treatment, but they may be considered in the setting of intracranial perineural spread or the reirradiation setting, when the radiation dosimetry is exceptionally complex. This review aims to provide an update on the current use of radiation in the treatment of locally advanced NMSCs.

Immunotherapy and other systemic therapies for cutaneous SCC

13-11-2019 – Alexander Guminski, Brian Stein

Journal Article

Contrary to the impression that non-melanoma skin cancer is a banal and relatively trivial malignancy it causes about 1% of all cancer deaths. Cutaneous Squamous Cell carcinoma (Cu
SCC) make up a significant part of these deaths either from incurable loco-regional disease or metastatic disease. As is typical of the disease itself, these patients are often of advanced age, but the immunocompromised from organ transplantation or haematological malignancy are important populations.

Systemic therapies have a long history in palliative therapy for Cu
SCC, but not a particularly extensively studied one. Cytotoxic chemotherapy is active with response rates derived from multiple small studies of 17–85%; as is often the case in solid tumour oncology responses are rarely durable. The Epidermal Growth Factor Receptor has been targeted with both small molecular inhibitors and monoclonal antibodies. Disease control rates of the order of 50–70% were seen but again durability remains an issue. Immunotherapy using interferon with retinoids also showed significant response rates in very small trials.

The high rates of mutation seen in Cu
SCC and relationship with immunosuppression suggested that checkpoint inhibitors might be active. Checkpoint inhibition immunotherapy with PD-1 antibodies like cemiplimab have demonstrated response rates of the order of 40% and durability is encouraging: response duration was over a year in 75% of responders in the initial trial. We review the latest data with current immunotherapy drugs and consider the future directions such therapy may take us as well as the role of these therapies in special populations.

Anatomical-based classification for transoral lateral oropharyngectomy

11-11-2019 – Armando De Virgilio, Se-Heon Kim, J. Scott Magnuson, Christopher Holsinger, Marc Remacle, Georges Lawson, Chen-Chi Wang, Giuseppe Mercante, Luca Malvezzi, Oreste Iocca, Pasquale Di Maio, Fabio Ferreli, Raul Pellini, Giuseppe Spriano

Journal Article

Purpose

The aim of the study is proposing a classification of different transoral lateral oropharyngectomy procedures in order to ensure better definitions of post-operative results.

Methods

The classification resulted from the consensus of the different authors and was based on anatomical-surgical principles.

Results

The classification comprises three types of lateral oropharyngectomy: type 1 is the resection of the palatine tonsil deep to the pharyngobasilar fascia; type 2 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle and the superior constrictor muscle; type 3 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle, the superior constrictor muscle, the buccopharyngeal fascia with extension to the pterygoid muscle and parapharyngeal space fat content. Based on the extension of the dissection we can use the suffix A (soft palate), B (posterior pharyngeal wall), C (base of tongue) and D (retromolar trigone).

Conclusion

The proposed classification introduces a simple and easy to use categorization of transoral lateral oropharyngectomies into three classes. Resection extensions are easily described using suffixes.

Survival outcomes with concomitant chemoradiotherapy in older adults with oropharyngeal carcinoma in an era of increasing human papillomavirus (HPV) prevalence

11-11-2019 – Diana J. Lu, Michael Luu, Anthony T. Nguyen, Kevin S. Scher, Jon Mallen-St. Clair, Alain Mita, Stephen L. Shiao, Allen S. Ho, Zachary S. Zumsteg

Journal Article

Background

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has dramatically increased in incidence and prevalence among patients aged 70 and older. There are virtually no data regarding outcomes in this population, and thus optimal therapy, including the role of chemotherapy for those undergoing radiotherapy (RT), remains unclear.

Methods

The National Cancer Database was queried for older adults (defined as age 70 years and older) with locally advanced OPSCC (c
T1-2N1-3, c
T3-4N0-3) diagnosed from 2010 to 2014 with known HPV-status undergoing definitive RT alone or chemoradiation (CRT).

Results

Overall, 1,965 older adults with locally advanced OPSCC met inclusion criteria, including 1,141 HPV-positive (58%) and 824 HPV-negative (42%) patients. 1,211 patients (62%) received CRT. In multivariable analysis, CRT was associated with improved survival in older patients when compared to RT alone (hazard ratio HR = 0.74, 95% confidence interval CI 0.64–0.86, P < 0.001). CRT was associated with improved survival in both HPV-positive (HR = 0.80, 95% CI: 0.64–1.00, P = 0.05) and HPV-negative (HR = 0.69, 95% CI: 0.56–0.85, P < 0.001) subgroups. There was no significant interaction between HPV status and the impact of CRT on survival (P interaction = 0.57).

Conclusions

Despite the radiosensitivity of HPV-positive OPSCC and the challenges in delivering CRT to older adults, CRT was associated with improved survival in older patients with HPV-positive OPSCC, similar in magnitude to the benefit in HPV-negative patients. As the incidence of HPV-positive OPSCC in older patients continues to increase, further studies are needed to investigate optimal therapeutic strategies in this population.

Use of a non-ICU specialty ward for immediate post-operative management of head and neck free flaps; a randomized controlled trial

05-11-2019 – B. Cervenka, L. Olinde, E. Gould, D.G. Farwell, M. Moore, M. Kaufman, A.F. Bewley

Journal Article

Objectives

Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively.

Materials and methods

A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared.

Results

131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs.

Conclusion

In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU.

Understanding approaches to measurement and impact of depth of invasion of oral cavity cancers: A survey of American Head and Neck Society Membership

05-11-2019 – Mustafa G. Bulbul, Joseph Zenga, Sidharth V. Puram, Osama Tarabichi, Anuraag S. Parikh, Mark A. Varvares

Journal Article

Objectives

To investigate methods used by head and neck surgeons to pre-operatively measure depth of invasion (DOI) in light of the new staging for oral cavity squamous cell carcinoma (OCSCC).

Materials and methods

A survey was designed and sent to all American Head and Neck Society (AHNS) members via an email link. The last response was recorded on January 16, 2019.

Results

We received 185 (13.3%) responses from 184 surgeons and 1 radiation oncologist. The majority of surgeons correctly identified DOI (78.9%) and indicated measuring DOI pre-operatively (86%). The most common methods for measuring DOI were manual palpation (32.5%) and full thickness biopsy (25.2%). In addition, most surgeons (84.7%) reported using a DOI threshold (in mm) as their primary criterion in their decision to pursue a neck dissection in the N0 neck. The most common reported threshold was 4 mm (37.4% of those that reported using DOI), however, the range varied from 2 to >10 mm. Two-thirds of surgeons considered DOI an important indicator for adjuvant therapy.

Conclusion

DOI is believed to be an important prognostic indicator guiding neck dissection and the need for adjuvant therapy. While most surgeons currently measure DOI pre-operatively, most use subjective methods. Future studies are needed to establish objective pre-operative DOI measurement techniques and to better inform the decision to perform prophylactic neck dissection, given the current majority practice of prophylactic neck dissection for DOI of 4 mm or greater.

Navigation-guided osteotomies improve margin delineation in tumors involving the sinonasal area: A preclinical study

05-11-2019 – Marco Ferrari, Michael J. Daly, Catriona M. Douglas, Harley H.L. Chan, Jimmy Qiu, Alberto Deganello, Stefano Taboni, Carissa M. Thomas, Axel Sahovaler, Ashok R. Jethwa, Wael Hasan, Piero Nicolai, Ralph W. Gilbert, Jonathan C. Irish

Journal Article

Objectives

To demonstrate and quantify, in a preclinical setting, the benefit of three-dimensional (3D) navigation guidance for margin delineation during ablative open surgery for advanced sinonasal cancer.

Materials and methods

Seven tumor models were created. 3D images were acquired with cone beam computed tomography, and 3D tumor segmentations were contoured. Eight surgeons with variable experience were recruited for the simulation of osteotomies. Three simulations were performed: 1) Unguided, 2) Guided using real-time tool tracking with 3D tumor segmentation (tumor-guided), and 3) Guided by 3D visualization of both the tumor and 1-cm margin segmentations (margin-guided). Analysis of cutting planes was performed and distance from the tumor surface was classified as follows: “intratumoral” when 0 mm or negative, “close” when greater than 0 mm and less than or equal to 5 mm, “adequate” when greater than 5 mm and less than or equal to 15 mm, and “excessive” over 15 mm. The three techniques (unguided, tumor-guided, margin-guided) were statistically compared.

Results

The use of 3D navigation for margin delineation significantly improved control of margins: unguided cuts had 18.1% intratumoral cuts compared to 0% intratumoral cuts with 3D navigation (p < 0.0001).

Conclusion

This preclinical study has demonstrated the significant benefit of navigation-guided osteotomies for sinonasal tumors. Translation into the clinical setting – with rigorous assessment of oncological outcomes – would be the proposed next step.

Development and validation of a nomogram incorporating selected systemic inflammation-based prognostic marker for complication prediction after vascularized fibula flap reconstruction

05-11-2019 – Zhongqi Liu, Haixuan Wu, Ning Liufu, Shi Cheng, Haoquan Huang, Chuwen Hu, Minghui Cao

Journal Article

Objective

To develop and validate a nomogram incorporating systemic inflammatory markers (the Albumin/NLR Score ANS) to predict postoperative complications after vascularized fibula flap reconstruction.

Patients and methods

A total of 238 patients who underwent vascularized fibula flap reconstruction between March 2012 and December 2016 were collected as the primary cohort. Univariable and multivariable analysis were performed to identify independent risk factors for postoperative complications. Backward stepwise logistic regression analysis was then applied with and without the ANS; and nomograms were established based on these criteria. Independent validation of these nomograms was carried out in an independent validation cohort including 106 consecutive patients from December 2016 and January 2018.

Results

Radiotherapy history (odds ratio OR = 0.336; 95% CI, 0.157–0.717; P = 0.005), the ANS (OR = 0.248; 95% CI, 0.093–0.661; P = 0.005) and fluid infusion rate over 24 h (OR = 0.671; 95% CI, 0.479–0.94; P = 0.02) were identified as independent risk factors for postoperative complications. A higher C-index was found in both the primary (0.759; 95% CI, 0.719–0.739) and validation cohort (0.704; 95% CI, 0.613–0.659) for the nomogram incorporating the ANS, and NRI was 0.496 (95% CI, 0.072–0.920; P = 0.022) comparing of these nomograms. Furthermore, a wider threshold probability (0.2–0.9) and superior clinical value were observed in the nomogram incorporating the ANS on the decision curve.

Conclusion

The ANS was an independent risk factor for postoperative complications associated with vascularized fibula flap reconstruction. The nomogram incorporating the ANS was established with better accuracy and showed more potential clinical benefit for the estimation of postoperative complications.

Management of retropharyngeal lymph node metastasis in oral cancer

05-11-2019 – Yu Oikawa, Yasuyuki Michi, Fumihiko Tsushima, Hirofumi Tomioka, Yumi Mochizuki, Takuma Kugimoto, Toshimitsu Osako, Hitomi Nojima, Misaki Yokokawa, Yoshihisa Kashima, Hiroyuki Harada

Journal Article

Objectives

Retropharyngeal lymph node (RPLN) metastasis is extremely rare, and prognosis is significantly poor in oral cancer. We retrospectively examined the management of RPLN metastases in oral cancer.

Materials and methods

A total of 1247 patients with oral cancer were treated at our department from January 2002 and December 2016. Among these patients, 374 (30%) had histologically positive lymph node metastases. Of these, 15 patients (1.2%) were diagnosed with RPLN metastases. We evaluated the diagnostic period, size, recurrence pattern, laterality, treatment, and therapeutic outcomes. The Kaplan–Meier method was used to determine overall survival (OS) among the RPLN metastasis group, cervical lymph node (CLN) metastases group, and treatment methods group for RPLN metastases.

Results

One patient had RPLN involvement at the initial treatment, and RPLN involvement in other patients was found subsequently. The mean duration in confirming RPLN metastases was 228 days (range, 50–867 days). Surgical therapy was performed in 5 patients, chemoradiotherapy in 7 patients, and best supported care (BSC) in 3 patients. The cumulative 5-year OS rate for the RPLN metastasis group (n = 15) was 38.1%, compared with the rate of 71.3% for the CLN group (n = 359). Regarding the therapeutic approach for RPLN metastases, OS rates were 80.0% (n = 5) in the surgical therapy group, 28.6% (n = 7) in the chemoradiotherapy group, and 0% (n = 3) in the BSC group.

Conclusion

Early detection and surgical treatment of RPLN metastases are associated with increased survival rate in oral cancer.

Advanced adenoid cystic carcinoma of the skull base – The role of surgery

05-11-2019 – Emily Guazzo, James Bowman, Sandro Porceddu, Lachlan Webb, Benedict Panizza

Journal Article

Background

Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with a propensity for perineural spread and diffuse soft tissue infiltration. In the head and neck this unique biological behaviour can result in skull base involvement. A lack of consensus regarding management of ACC involving the skull base in conjunction with the technical and reconstructive challenges of oncological resection in this region has led to variation in practice between institutions.

Method

Retrospective multicentre review of patients with advanced ACC infiltrating the skull base, treated surgically by the Queensland Skull Base Unit between 2005 and 2017, with a minimum follow up time of 24  months.

Results

32 patients were treated for ACC with skull base involvement with oncological resection and post-operative radiation in the study period with a median follow up of 82.18  months (33.11–159.53 months). 5 and 10  year locoregional control were both 88.2% (95% CI 67.5–96.1) despite a high rate of microscopically positive margins (81.3%). Metastatic disease rates were high, resulting in low rates of disease free survival (DFS) (53.0% at 5 years (95% CI 33.7–69.0) and 23.0% at 10 years (9.5–39.8)).

Overall survival (OS) was high (5 year 91.8% (95% CI 71.1–97.9), 10 year 63.7% (95% 37.5–81.2)), despite the advanced nature of disease.

Conclusion

High rates of locoregional control can be achieved in skull base ACC with oncological resection of disease and post-operative radiation. Whilst disease recurrence rates are high, a majority of recurrence is metastatic and does not confer poor intermediate term overall survival.

Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma primary tumors is associated with nodal metastasis

11-11-2019 – Anuraag S. Parikh, Sidharth V. Puram, William C. Faquin, Jeremy D. Richmon, Kevin S. Emerick, Daniel G. Deschler, Mark A. Varvares, Itay Tirosh, Bradley E. Bernstein, Derrick T. Lin

Journal Article

Objectives

Quantify by immunohistochemistry (IHC) a partial epithelial-to-mesenchymal transition (p-EMT) population in oral cavity squamous cell carcinoma (OCSCC) and determine its predictive value for lymph node metastasis.

Methods

Tissue microarrays (TMA) were created using 2 mm cores from 99 OCSCC patients (47 with low volume T2 disease, 52 with high volume T4 disease, and ∼50% in each group with nodal metastasis). IHC staining was performed for three validated p-EMT markers (PDPN, LAMB3, LAMC2) and one marker of well-differentiated epithelial cells (SPRR1B). Staining was quantified in a blinded manner by two reviewers. Tumors were classified as malignant basal subtype based on staining for the four markers. In this subset, the p-EMT score was computed as the average of p-EMT markers.

Results

84 tumors were classified as malignant basal. There was 87% inter-rater consistency in marker quantification. There were associations of p-EMT scores with higher grade (2.15 vs. 1.92, p = 0.04), PNI (2.13 vs. 1.83, p = 0.003), and node positivity (2.09 vs. 1.87, p = 0.02), including occult node positivity (56% vs. 19%, p = 0.005). P-EMT was independently associated with nodal metastasis in a multivariate analysis (OR 3.12, p = 0.039). Overall and disease free survival showed trends towards being diminished in the p-EMT high group.

Conclusions

IHC quantification of p-EMT in OCSCC primary tumors is reliably associated with nodal metastasis, PNI, and high grade. With prospective validation, p-EMT biomarkers may aid in decision-making over whether to perform a neck dissection in the N0 neck and/or for adjuvant therapy planning.

Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice

05-11-2019 – Katsuhisa Sekido, Kei Tomihara, Hidetake Tachinami, Wataru Heshiki, Kotaro Sakurai, Rohan Moniruzzaman, Shuichi Imaue, Kumiko Fujiwara, Makoto Noguchi

Journal Article

Objectives

Aging has been suggested to be associated with immune dysregulation. An understanding of alterations in the host immunity with advancing age is, therefore, important for designing immune therapy for elderly cancer patients. In this context, not much is known about age-associated alterations in the immune system in oral cancer.

Methods

To evaluate age-associated alterations in the immune system, which might affect anti-tumor immune responses in oral cancer, we performed a comparative analysis of the proportion of different immune cells, the proliferative capacity of T cell compartment, and the response against immune therapies targeting immune check point molecules between young and aged oral cancer-bearing mice.

Results

The proportion of immune regulatory cells, such as regulatory T cells and myeloid derived suppressor cells, was significantly increased in aged mice compared to that in young mice. Moreover, the expression of PD-1 and CTLA-4 on both CD4+ and CD8+ T cells was elevated in aged mice compared to that in young mice, and the proliferative abilities of CD4+ and CD8+ T cells derived from aged mice were significantly reduced following stimulation of T-cell receptors. Moreover, tumor growth was significantly enhanced in aged mice compared to that in young mice. However, immunotherapies targeting PD-1, CTLA-4, and PD-L1 resulted in faster tumor regression in aged mice than in young mice.

Conclusions

Together, our results indicate that age-associated alterations in the immune system are directly associated with the impairment of anti-tumor immunity in aged mice bearing oral cancer, and might facilitate the progression of the tumor.

Reconstruction of maxillectomy and midfacial defects using latissimus dorsi-scapular free flaps in a comprehensive cancer center

05-11-2019 – A. Moya-Plana, M. Veyrat, J.F. Honart, K. de Fremicourt, H. Alkhashnam, B. Sarfati, F. Janot, N. Leymarie, S. Temam, F. Kolb

Journal Article

Background

The standard of care for sinonasal malignancies is a large surgical resection followed by radiotherapy. Midfacial defects resulting from maxillectomy require a complex reconstruction procedure. Given their adaptability, chimeric flaps such as latissimus dorsi-scapular (LDS) free flaps appear to be a good option.

Material & methods

We performed a single-center retrospective study of consecutive patients with sinonasal cancers where a LDS free flap was used for reconstruction. We assessed the postoperative complications and the functional, aesthetic and oncologic outcomes.

Results

Eighty-four patients were included. Primary tumors were staged as T4a in 68% of cases; 38.3% of the patients received induction chemotherapy and 82.7% received adjuvant radiotherapy. Based on our classification of midfacial and palatal defects, the majority of the patients (69%) had a type IIa with interruption of the three facial pillars. The orbital floor was removed in 55.9% of cases. The median follow-up was 45 months. Total flap necrosis with no possible revascularization occurred in 5.9% of cases. For the orbital reconstruction, a revision procedure was needed for necrosis and/or infection of the costal cartilage graft in eight cases (17%). More than 90% of the patients had no functional disorders regarding speaking, swallowing and chewing. Soft palate involvement was a prognostic factor of speech (p < 10−4) and swallowing (p = .005) disorders. Dental rehabilitation was realized in 70.2% of the patients. No severe complications were observed in the donor site, except for one seroma.

Conclusion

A LDS free flap is a reliable technique for the reconstruction of complex midfacial defects.

Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis

02-11-2019 – Daisuke Sano, Teruhiko Tanabe, Akira Kubota, Shunsuke Miyamoto, Yuji Tanigaki, Kenji Okami, Masanori Komatsu, Ryo Ikoma, Kazumasa Suzuki, Yoshihiro Akazawa, Sei Kobayashi, Yoshihiro Yamada, Nobuhiko Oridate

Journal Article

Objectives

This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan.

Materials and Methods

This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared.

Results

Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013).

Conclusions

The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.

A comparative study between submandibular-facial artery island flaps (including perforator flap) and submental artery perforator flap: A novel flap in oral cavity reconstruction

02-11-2019 – Xin-rong Ou, Tong Su, Long Huang, Can-hua Jiang, Feng Guo, Ning Li, An-jie Min, Xin-chun Jian

Journal Article

Objective

The purpose of this study was to introduce submandibular-facial artery island flaps (S-FAIF), including the perforator flap, and to evaluate their application for intraoral reconstruction in comparison with submental artery perforator flaps (SMAPF).

Methods

Ninety-six patients who underwent intraoral reconstruction using an S-FAIF (n = 34) or SMAPF (n = 62) after cancer resection were recruited in this study. The flap characteristics (viz., pedicle length, flap size, venous drainage pattern, and harvest time), short-term outcomes (viz., flap partial loss, intraoral wound dehiscence, fistula, and wound infection), and long-term morbidity (viz., facial nerve palsy, neck motion restriction, and hair growth) were compared.

Results

Nine S-FAIFs were authentic perforator flaps pedicled by level Ⅰ facial artery perforators, while the rest were island flaps based on level Ⅱ facial artery perforators. The survival rates of S-FAIF and SMAPF were both 100 percent. Flap partial loss occurred in two patients in each group. The pedicle length of S-FAIF was shorter than that of SMAPF (p < 0.001). Statistics analysis revealed no significant difference regarding flap size, venous drainage pattern, short-term outcomes, neck motion restriction, or facial nerve palsy between the groups. S-FAIF required less harvest time (p < 0.001) and experienced less hair growth when compared to SMAPF (p = 0.011).

Conclusions

The S-FAIF is a robust and reliable novel flap and on par with SMAPF for reconstruction of small and medium-sized intraoral defects. It is preferred to SMAPF when technical requirements for flap harvest and hair problems are considered. It should be supplemented to the armamentarium for intraoral reconstruction.

Prognostic value of radiologic extranodal extension and its potential role in future N classification for nasopharyngeal carcinoma

28-10-2019 – Tianzhu Lu, Yujun Hu, Youping Xiao, Qiaojuan Guo, Shao Hui Huang, Brian OSullivan, Yanhong Fang, Jingfeng Zong, Ying Chen, Shaojun Lin, Yunbin Chen, Jianji Pan

Journal Article

Purpose

We evaluated the prognostic value of various grades of radiologic extranodal extension (r
ENE) and their potential roles in N-classification refinement for nasopharyngeal carcinoma (NPC).

Methods and Materials

All NPC patients treated with IMRT in our institution between 2005 and 2011 were included. Pre-treatment MR of c
N+ cases were reviewed and r
ENE was recorded as
G0: lymph nodes (LNs) without r
ENE; G1: tumor infiltrating beyond individual nodal capsule(s) into the surrounding fat plane; G2: coalescent nodal mass with unequivocal evidence of r
ENE; G3: tumor infiltrating beyond nodal capsule into adjacent structures. Multivariable analysis (MVA) assessed prognostic value of r
ENE for distant metastasis (DM) and death adjusted for age, gender, LDH, T-classification, N-classification, and chemotherapy cycles.

Results

A total of 1390 of 1616 (86%) NPC were c
N+, and r
ENE was detected in 826/1390 (59%) patients: 256 (18.4%) G1-r
ENE, 487 (35%) G2-r
ENE, and 83 (6%) G3-r
ENE. MVA confirmed that G2-/G3-r
ENE had increased risk of DM (HR: 2.05/3.18, both p < 0.001) and death (HR: 1.62/2.39, p = 0.002/p < 0.001), while G1-r
ENE was non-prognostic (DM: p = 0.172; death: p = 0.320). We propose a refined N: New-N1: N1/N2 without G2-/G3-r
ENE; New-N2: N1_G2-r
ENE; New-N3: N2_G2-r
ENE, N1/N2_G3-r
ENE, or N3. The New-N classification had a lower AIC and higher c-index for DM (AIC: 3809.6 vs 3830.9; c-index: 0.700 vs. 0.677) and death (AIC: 3693.8 vs. 3705.9; c-index: 0.735 vs. 0.725) versus TNM-8 N.

Conclusions

G2- and G3-r
ENE are independently prognostic for DM and death in NPC. Compared to the TNM8 N-classification, a refined N-classification incorporating G2- and G3-r
ENE improves prognostication of DM and mortality risk.

Symptom burden among head and neck cancer patients in the first year after diagnosis: Association with primary treatment modality

21-10-2019 – Catherine O. Allen-Ayodabo, Antoine Eskander, Laura E. Davis, Haoyu Zhao, Alyson L. Mahar, Irene Karam, Simron Singh, Vaibhav Gupta, Lev D. Bubis, Lesley Moody, Lisa Barbera, Natalie G. Coburn

Journal Article

Purpose

Head and neck cancer (HNC) and its treatment affects quality of life, with significant symptom burden. The main objectives of this study were to examine symptom trajectories of HNC patients by treatment and to identify factors associated with high ESAS scores.

Methods and materials

We conducted a retrospective cohort study in patients diagnosed with HNC in Ontario, Canada from 2007 to 2015 using linked health administrative databases. The primary outcome was a monthly patient self-reported moderate-to-severe (≥4) symptom score in the year following diagnosis. Multivariable Modified Poisson regression analyses with robust variance were used to investigate factors associated with moderate-to-severe scores.

Results

Of 13,827 HNC patients identified, 4793 had ≥1 ESAS assessment within 12 months of cancer diagnosis. Overall, 60% (n = 2708) and 65% (n = 2903) of patients reported moderate-to-severe pain and poor appetite, respectively. The proportion of patients reporting a score ≥4 increased significantly during treatment and was most pronounced for those who received chemoradiation (CRT). On multivariable analysis, patients who were female (Relative Risk (RR) 1.15, 95% CI 1.08–1.23, received CRT, had a higher comorbidity burden (RR 1.31, 1.23–1.39), and had a diagnosis of oropharyngeal (1.10, 1.02–1.19), or oral cavity cancer (1.31, 1.19–1.45), were at an increased risk of reporting severe pain scores (p < 0.01 for all).

Conclusion

The majority of HNC patients report high pain scores, with symptom burden highest during the treatment phase, and especially for patients who received radiation or chemoradiation. This large study highlights the need for proactive symptom management during the HNC patients cancer journey.

Impact of contralateral lymph nodal involvement and extranodal extension on survival of surgically managed HPV-positive oropharyngeal cancer staged with the AJCC eighth edition

21-10-2019 – Joseph A. Miccio, Vivek Verma, Jacqueline Kelly, Benjamin H. Kann, Yi An, Henry S. Park, Antoine Eskander, Barbara Burtness, Zain Husain

Journal Article

Objectives

Contralateral lymph node (LN) involvement is a prognostic factor in clinical staging of oropharyngeal squamous cell carcinoma (OPSCC), while pathologic nodal staging in the AJCC 8th edition for human papillomavirus-mediated OPSCC (HPV + OPSCC) focuses exclusively on the number of involved LNs (p
LN+). This study assessed if the presence of contralateral p
LN+ adds prognostic importance to the number of p
LN+.

Materials and methods

The National Cancer Database was queried for p
LN+ HPV + OPSCC treated with surgery with 10 or more LN dissected. Data were evaluated with Cox regression, propensity score matching (PSM), and Kaplan-Meier overall survival (OS) analysis.

Results

Of 3407 patients, 152 (4.5%) patients had contralateral p
LN+. Subjects with contralateral p
LN+ had higher p
T/p
N stage, more positive margins, extranodal extension (ENE), and lymphovascular invasion (LVI) (all p < 0.05). On univariate analysis, contralateral p
LN+ trended toward worse OS (HR 1.58, 95% CI 0.98–2.55, p = 0.061). In the multivariable model (controlling for age, comorbidities, T-stage, N-stage, LN size, ENE, LVI, margin status and adjuvant therapy), LN laterality had no impact on OS (HR 0.87, 95% CI 0.52–1.45, p = 0.520). Further PSM analysis confirmed that contralateral p
LN+ is not associated with OS in this population (HR 0.79, 95% CI 0.41–1.53, p = 0.494).

Conclusion

This study supports the AJCC 8th edition pathologic staging for HPV + OPSCC by observing that LN laterality is not associated with OS. ENE was associated with inferior OS and should be considered for future staging systems. Further study should be directed at the importance of nodal size in this population.

Graphical abstract

Graphical abstract for this article

Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer

05-11-2019 – Ester Orlandi, Nicola Alessandro Iacovelli, Vincenzo Tombolini, Tiziana Rancati, Antonella Polimeni, Loris De Cecco, Riccardo Valdagni, Francesca De Felice

Journal Article, Review

In the last decade, human microbiome research is rapidly growing involving several fields of clinical medicine and population health. Although the microbiome seems to be linked to all sorts of diseases, cancer has the biggest potential to be investigated.

Following the publication of the National Institute of Health – Human Microbiome Project (NIH-HMP), the link between Head and Neck Cancer (HNC) and microbiome seems to be a fast-moving field in research area. However, robust evidence-based literature is still quite scarce. Nevertheless the relationship between oral microbiome and HNC could have important consequences for prevention and early detection of this type of tumors.

The aims of the present review are: (i) to discuss current pre-clinical evidence of a role of oral microbiome in HNC; (ii) to report recent developments in understanding the human microbiomes relationship with HNC oncogenesis; (iii) to explore the issue of treatment response and treatment toxicity; (iv) to describe the role of microbiota as potentially modifiable factor suitable for targeting by therapeutics.

Further studies are needed to better establish the causal relationship between oral microbiome and HNC oncogenesis. Future trials should continue to explore oral microbiome in order to build the scientific and clinical rationale of HNC preventative and ameliorate treatment outcome.

Immunotherapy for head and neck cancer: Recent advances and future directions

05-11-2019 – John D. Cramer, Barbara Burtness, Robert L. Ferris

Journal Article, Review

Three randomized phase III trials have now conclusively proven that exposure to a PD-1 inhibitor prolongs survival in recurrent/metastatic (R/M) HNSCC, and it is clear that such agents should be used in the management of all patients who do not have contraindications to their use. Two of these phase III randomized trials showed that the anti-PD1 antibodies nivolumab and pembrolizumab were superior to investigators′ choice chemotherapy in second-line platinum-refractory R/M HNSCC. Recently, a third phase III randomized trial, KEYNOTE-048, showed that pembrolizumab with chemotherapy was superior to the EXTREME regimen (cis- or carboplatin, 5-fluorouracil (5-FU) and cetuximab) in all patients, and pembrolizumab monotherapy was superior in patients whose tumors express PD-L1 in first-line R/M HNSCC. Pembrolizumab is now approved as monotherapy in PD-L1 expressing disease (combined positive score ≥1) or in combination with chemotherapy for all patients with R/M HNSCC. Thus, PD-L1 biomarker testing will be routinely used in R/M HNSCC, and this employs a scoring system that incorporates immune cell staining, referred to as the combined positive score (CPS). Additionally, for the 85% of patients with PD-L1 CPS ≥1, clinical judgment will guide the choice of pembrolizumab monotherapy or pembrolizumab plus chemotherapy, until more detailed clinical data are forthcoming to better inform this decision. In this article we discuss the clinical trials leading to these therapeutic advances and we will review initial results from clinical trials in previously untreated, locally advanced disease, and those using novel combinations of checkpoint inhibitors, co-stimulatory agonists, and therapeutic vaccines.

miRNAs in liquid biopsy for oral squamous cell carcinoma diagnosis: Systematic review and meta-analysis

23-11-2019 – O. Rapado-González, C. Martínez-Reglero, A. Salgado-Barreira, R. López-López, M.M. Suárez-Cunqueiro, L. Muinelo-Romay

Journal Article, Review

Oral squamous cell carcinoma (OSCC) is often diagnosed at advanced stages and is associated with poor survival rates. Increasing evidence suggests that micro
RNAs (mi
RNAs) present in liquid biopsies could be potential biomarkers for non-invasive OSCC diagnosis. Here, we performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of blood and salivary mi
RNAs in detecting OSCC. A literature search using PubMed EMBASE, Web of Science, LILACS, Scopus, and the Cochrane Library was undertaken up to February 2019. Study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess the heterogeneity. Twenty-five study units from 16 articles with 2562 subjects were included in this meta-analysis. The pooled sensitivity and specificity of blood and salivary mi
RNAs in the diagnosis of OSCC were 0.78 (95% CI: 0.76–0.80) and 0.82 (95% CI: 0.79–0.84), respectively, and the pooled positive and negative likelihood ratios were 4.31 (95% CI: 3.38–5.51) and 0.25 (95% CI: 0.20–0.32), respectively. The overall area under the curve was 0.91 (95% CI: 0.88–0.93), with a diagnostic odds ratio of 21.46 (95% CI: 13.37–34.45). These findings provide evidence regarding the potential clinical application of blood and salivary mi
RNAs as a novel, non-invasive, and accurate diagnostic tool for OSCC.

Single-cell sequencing and its applications in head and neck cancer

07-11-2019 – Zongtai Qi, Thomas Barrett, Anuraag S. Parikh, Itay Tirosh, Sidharth V. Puram

Journal Article, Review

Head and neck squamous cell carcinoma (HNSCC), like many tumors, is characterized by significant intra-tumoral heterogeneity, namely transcriptional, genetic, and epigenetic differences that define distinct cellular subpopulations. While it has been established that intra-tumoral heterogeneity may have prognostic significance in HNSCC, we are only beginning to describe and define such heterogeneity at a cellular resolution. Recent advances in single-cell sequencing technologies have been critical in this regard, opening new avenues in our understanding of more nuanced tumor biology by identifying distinct cellular subpopulations, dissecting signaling within the tumor microenvironment, and characterizing cellular genomic mutations and copy number aberrations. The combined effect of these insights is likely to be robust and meaningful changes in existing diagnostic and treatment algorithms through the application of novel biomarkers as well as targeted therapeutics. Here, we review single-cell technological and computational advances at the genomic, transcriptomic, and epigenomic levels, and discuss their applications in cancer research and clinical practice, with a specific focus on HNSCC.

Is no biopsy appropriate for oral potentially malignant lesion(s) without loss of autofluorescence using VELscope®? A large prospective diagnostic study

01-12-2019 – James Sciubba, Joel Epstein

Editorial

Nuclear atypia in Pindborg tumor: An unexplored phenomenon of a well recognized entity

27-11-2019 – Deepak Pandiar, Rahul Anand, Mala Kamboj

Letter

A new wave of oral cancer epidemic among youth in Pakistan

25-11-2019 – Tayyaba, Nida Akram, Fawad Ur Rehman

Letter

Teeth extraction revealing mandibular IgA-multiple myeloma recurrence

17-11-2019 – Adriana Handra-Luca

Letter

Radiation induced hypothyroidism – Why is early intervention necessary?

12-11-2019 – Kshitij Aggarwal, Shalini Thakur, Sameep S. Shetty, Vishal Rao

Letter

Response to R. Jayaraj

07-11-2019 – Etienne Dauzier, Benjamin Lacas, Pierre Blanchard, Anne Aupérin, Jean-Pierre Pignon

Letter

Complex midfacial defects: Is the extended Abbé flap the ideal solution to a tough problem?

07-11-2019 – Konstantinos Mantsopoulos, Heinrich Iro, Jannis Constantinidis

Letter

Objectives

The aim of this study was to investigate the role of the extended Abbé flap in the reconstruction of complex midfacial defects (upper lip, nasal base and medial cheek). We describe our personal experience with this method and present some interesting aspects from the relevant literature.

Materials and methods

Between 2003 and 2017 we retrospectively evaluated the records of all patients with defects of the upper lip and nasal base after the resection of malignant tumors or traumata and reconstruction by means of the extended Abbé flap. We looked for information on the origin of the defect, the functional result, the aesthetic outcome and postoperative complications. The functional result of the reconstruction of the oral commissure was assessed with regard to postoperative subjective speech integrity, preservation of competence of the oral sphincter and lip sensation. The aesthetic outcome was evaluated with regard to limitations in facial expression and scar formation.

Results

The study included 8 patients. Follow–up in the oncological cases was 85 months (range: 20–150 months). No tumor recurrences were detected. All patients achieved normal oral competence and mouth opening. No cases of blunting or microstomia were detected.

Conclusion

Reconstruction of the upper lip and nasal base with the extended Abbé flap is associated with an outstanding functional outcome that is cosmetically very acceptable.

Verrucous dysplasia or verrucous hyperplasia: Clarity in terminology

31-10-2019 – Aakruti Shah, Rajiv S. Desai, Pankaj Shirsat, Shivani Bansal, Pooja Prasad

Letter

Innovations in risk-stratification and treatment of Veterans with oropharynx cancer; roadmap of the 2019 Field Based Meeting

28-10-2019 – V.C. Sandulache, Y.L. Lei, L.E. Heasley, M. Chang, C.I. Amos, E.M. Sturgis, E. Graboyes, E.Y. Chiao, N. Rogus-Pulia, J. Lewis, A. Madabhushi, M.J. Frederick, A. Sabichi, M. Ittmann, W.G. Yarbrough, C.H. Chung, R. Ferrarotto, Weiyuan Mai, H.D. Skinner, U. Duvvuri

Editorial

Immediate deltopectoral flap salvage of a failing anterolateral thigh free flap

28-10-2019 – Bipin T. Varghese, Sowrabh Arora

Letter

Co-occurrence of Warthin’s tumor with oral squamous cell carcinoma – Overlapping risk factors and implications

28-10-2019 – Harshada Bhatlawande, Karishma Madhusudan Desai, Alka Dinesh Kale, Punnya Angadi, Seema Hallikerimath, Rebekah Chibborah

Letter

Tubulopapillary hidradenoma-like tumor of the mandible: Two case reports of an underrecognized entity

22-10-2019 – Ming Zeng, Xiaolong Guo, Xinming Chen, Shaodong Yang

Letter

Tubulopapillary hidradenoma-like tumor of the mandible is extremely rare, with only 3 cases published in the English-language literature. The clinicopathological characteristics and histogenesis of this tumor are unclear. Few pathologists and perhaps fewer clinicians are familiar with this entity, and it is likely underrecognized and under-reported. Herein, we present two additional cases, both misdiagnosed as malignancies preoperatively and postoperatively by different unwary pathologists. Awareness and knowledge of this enigmatic entity and its clinical and radiographic features, together with careful morphological assessment should enable the correct diagnosis and prevent unnecessary treatment.

Immune checkpoint inhibitors: For how long do we need to release the brakes to achieve the optimum acceleration of immune-mediated anti-tumor response?

23-10-2019 – Ammar Sukari, Misako Nagasaka

Letter

In recent years, cancer immunotherapy has emerged as the fourth pillar of cancer therapy alongside surgery, chemotherapy and radiotherapy. We here report an unusual scenario of a patient with advanced metastatic non-small cell lung cancer who was lost to follow up after two cycles of chemo-immunotherapy who later returned to clinic with complete response; suggesting that in some, all that was needed may have been just a few doses of therapy to “release the breaks.”

Ibrutinib-associated oral ulcers

21-10-2019 – Grigorios Thermos, Konstantinos I. Tosios

Letter

Second field tumors in oral submucous fibrosis: An abandoned phenomenon?

21-10-2019 – Arpan K. Shah, Sandeep B. Patil

Letter

Oral melanomas in HIV-positive patients: Report of two cases and review of the literature

03-08-2019 – Thayná Melo de Lima Morais, Ciro Dantas Soares, Arthur Eric Costa Wanderley, Catarina Rodrigues Rosa de Oliveira, Camila Maria Beder Ribeiro, Oslei Paes de Almeida, Maria Goretti Freire de Carvalho, Sonia Maria Soares Ferreira

Letter

Oral melanoma in HIV-positive patients is exceedingly rare, with only two cases reported in the literature published in English. Herein, we report two additional cases of oral melanomas which occurred as oral masses in the upper gingiva and hard palate in 35- and 27-year-old HIV-positive women. Significant thrombocytopenia, anemia, reduced CD4 cells, and high HIV load occurred in both patients. Microscopically, the lesions showed a variable proliferation of fusiform and epithelioid-pigmented cells, with cellular pleomorphism and high mitotic index. The diagnosis of melanoma was supported by positive immunoreactivity for S-100, Melan
A, and HMB-45. Both cases had an unfavorable outcome, and the patients died a few months after the initial diagnosis. Because of its rarity, oral melanoma occurring in HIV-positive patients can pose problems in diagnosis and should be clinically distinguished from Kaposi’s sarcoma, which is more common in the context of the immunodeficiency syndrome.

Incidental finding of tongue cancer in a PET scan: A fusion of anatomic and metabolic imaging

29-07-2019 – Sameep S. Shetty, Akshay Kudpaje, Vishal Rao

Letter

Podoplanin and ABCG2 expression in oral erythroplakia revisited: Potential evidence for cancer stem cells driving the process of field cancerization

14-07-2019 – Xi Yang, Linjun Shi, Zengtong Zhou, Wei Liu

Letter

A model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed. Podoplanin and ABCG2 are promising marker of CSCs for head and neck cancer. We revisited the correlation of the two markers with the follow-up data of the patients with oral erythroplakia (OE). Strikingly, we observed that the expression of podoplanin and ABCG2 within a single pre-neoplastic OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, thus to some extent demonstrating the concept of field cancerization. Collectively, a point to highlight was that a preliminary evidence that provided by this revisited study supported the perspective on cancer stem cells driving the process of field cancerization.

Current evidence on DNA aneuploidy cytology in noninvasive detection of oral cancer

14-07-2019 – Linjun Shi, Yufeng Wang, Chenxi Li, Wei Liu

Letter

DNA-aneuploidy cytology as a promising noninvasive tool in diagnosing oral precancer and cancer has been proposed in 2015. In this letter, we identified 9 studies on DNA aneuploidy cytology with special emphasis on using fresh tissue sample in detection of oral precancer and cancer. Evidence was updated as follows, for detection of OSCC in general oral lesions, the pooled sensitivity and specificity was 84.8 and 99.0 respectively; for discrimination of dysplasia and OSCC form oral lesions, the sensitivity and specificity was 75.7 and 76.8 respectively. On the whole, current evidence on the theme is not robust, and multicenter prospective studies are needed to consolidate the evidence.

Nivolumab in patients with rare head and neck carcinomas: A single center’s experience

14-07-2019 – Stefania Kokkali, Anna Ntokou, Maria Drizou, Konstantina Perdikari, Panagiotis Makaronis, Elena Katsarou, Nektarios Koufopoulos, Alexandros Tzovaras, Alexandros Ardavanis

Letter

Immunotherapy (IO) with anti-PD1 inhibitors is available for the treatment of recurrent/metastatic squamous cell carcinomas of the head and neck (SCCHD) since 2016. Both nivolumab and pembrolizumab were tested in phase 3 randomized trials in adults progressing on or after platinum-based therapy and were found to confer an overall survival benefit compared to investigator’s choice. However, very limited data exist concerning IO use in rare subtypes of head and neck carcinoma, like salivary gland carcinoma.

We retrospectively collected clinical data of all patients diagnosed with rare subtypes of head and neck carcinoma, who were treated with immune checkpoint inhibitors in our department during the last 5 years. We analyzed safety and efficacy of these therapies.

We identified six patients who received nivolumab for recurrent or metastatic head and neck carcinomas, between 31 and 57 years old. All patients had received at least one line of platinum-chemotherapy, as well as radiation therapy. Treatment was administered every 2 weeks, at a dose of 3 mg per kilogram of body weight. Number of nivolumab cycles varied between 2 and 18. Progression-free survival varied from 1 to 12 months and overall survival from 4 to 24 months. Tolerance was very good, except for one case of diabetes and hypothyroidism requiring medication.

There is currently insufficient evidence regarding the optimal treatment of the rare non-squamous cell carcinoma of the head and neck. Our case series supports a role for immunotherapy in these patients. However, larger collaborative studies are needed to evaluate this treatment.

Different responses to nivolumab therapy between primary and metastatic tumors in a patient with recurrent hypopharyngeal squamous cell carcinoma

14-07-2019 – Kiminobu Sato, Takeharu Ono, Fumihiko Sato, Akihiko Kawahara, Koichi Azuma, Toshihiko Kawaguchi, Jun Akiba, Hirohito Umeno

Letter

We report the case of a 70-year-old man with primary and metastatic tumors, showing clinically progressive disease and complete response to nivolumab therapy, respectively. He underwent total pharyngo-laryngectomy, bilateral neck dissection, and reconstruction with free-jejunum after nivolumab therapy failure, and had no recurrent or newly arising lesions 8 months after the surgery. Immunohistochemistry analysis revealed that metastatic neck tumor with the clinical complete response to nivolumab showed higher PD-L1 expression with higher CD8+ TIL density, while primary lesion with progressive disease showed lower PD-L1 expression with lower CD8+ TIL density. This represents the first case reported on head and neck squamous cell carcinoma treated with salvage surgery after nivolumab therapy failure.

Comment on “Resolution without surgery of an advanced stage of medication-related osteonecrosis of the jaw (MRONJ) in a patient who could not suspend her treatment for osteoporosis”, by Sarmiento (2019)

07-07-2019 – Patrícia Carlos Caldeira

Letter

Combined parameter SUVmax/ADCmean predicts microvessel density in head and neck squamous cell carcinoma. Preliminary results

08-07-2019 – Alexey Surov, Hans Jonas Meyer, Anne-Kathrin Höhn, Andreas Wienke, Osama Sabri, Sandra Purz

Letter

Complete response with neoadjuvant avelumab in Merkel cell carcinoma – A case report

07-07-2019 – Nadine Abdallah, Misako Nagasaka, Tahmida Chowdhury, Kunil Raval, Jeffrey Hotaling, Ammar Sukari

Letter

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin malignancy. We report here a case of localized MCC achieving pathologic complete response upon treatment with avelumab in the neoadjuvant setting. Preclinical and clinical studies have revealed a close relationship between MCC and the immune system, thus supporting a role for PD-1/PD-L1 inhibitors in MCC. This neoadjuvant use of PD-1/PD-L1 inhibitors can avoid potentially disfiguring surgery in MCC. As the incidence of MCC is rising, clinical trials are needed to evaluate the efficacy and safety of immunotherapy in resectable disease.

Tongue cancer: A discrete oral cavity subsite

06-07-2019 – Sameep S. Shetty, Akshay Kudpaje, Rama Jayaraj, Vishal Rao, Prit Kiran Shah

Letter

Intraoperative flow cytometry for head and neck lesions. Assessment of malignancy and tumour-free resection margins

06-07-2019 – George Vartholomatos, Lentiona Basiari, George Exarchakos, Ioannis Kastanioudakis, Ioannis Komnos, Maria Michali, Georgios S. Markopoulos, Anna Batistatou, Alexandra Papoudou-Bai, George A. Alexiou

Letter

Head and neck cancer poses a significant health problem worldwide. We set out to investigate the value of rapid intraoperative cell cycle analysis by flow cytometry for the intraoperative characterization of head and neck lesions and surgical margins. Seventy patients with head and neck lesions suspicious of malignancy were included in the study. There were 31 neoplastic and 39 benign lesions. Flow cytometry permitted the intraoperative detection of neoplastic lesions within 6 min with high sensitivity and specificity based on cell cycle fractions. In the cases in which surgical margins were assessed, intraoperative flow cytometry had complete concordance with pathology. Intreoperative flow cytometry is a novel promising technique for rapid intraoperative characterization of malignancy and tumour free resection margins in head and neck lesions.

“Cowdens syndrome: A case report”

03-07-2019 – Zhongfeng Liu, Qi Wang, Jun Li

Letter

Agreement between skeletal muscle mass measurements using computed tomography imaging and magnetic resonance imaging in head and neck cancer patients

30-06-2019 – N. Chargi, E. Ansari, L.F.J. Huiskamp, G. Bol, R. de Bree

Letter

Medication related osteonecrosis of jaw in a leukemia patient undergoing systemic arsenic trioxide therapy: A rare case report

01-07-2019 – Mathangi Kumar, Ravindranath Vineetha, Adarsh Kudva

Letter

Osteonecrosis of the jaw is a potential side effect of certain pharmaceutical agents used in the field of medicine. Early diagnosis and effective management of this condition can be challenging to the clinicians. Bisphosphonates and other anti-angiogenic agents are the most common drugs that are attributed to cause medication-related osteonecrosis of the jaw. In the past, arsenic-based compounds were commonly used local agents for pulp devitalization therapy. Arsenic is also one of the components of the chemotherapeutic regimen in the management of refractory leukemia. Although local diffusion of the arsenic compounds is known to cause osteonecrosis, there are no reports of the same caused by its systemic administration. Here, we present the first ever case of mandibular bone necrosis in a patient with acute promyelocytic leukemia who underwent systemic arsenic trioxide therapy.