Oral Oncology

Oral Oncology

Role of zoledronic acid in nasopharyngeal carcinoma patients with bone-only metastasis at diagnosis

20-08-2019 – Xue-Song Sun, Chao Lin, Yu-Jing Liang, Qiu-Yan Chen, Lin-Quan Tang, Hai-Qiang Mai

Journal Article

Objective

We aimed to investigate whether zoledronic acid (ZA) can prevent skeletal-related events (SREs) and offer survival benefits for nasopharyngeal carcinoma (NPC) patients with bone-only metastasis at diagnosis.

Materials and Methods

A total of 228 newly diagnosed NPC cases with bone-only metastasis were eligible for this retrospective study. Using the propensity score method (PSM) method, a well-balanced cohort was created for further analysis. Overall survival (OS) was the primary endpoint. The difference in survival was evaluated using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all­cause mortality were derived from a Cox regression model. Cumulative incidence competing risk analyses using Fine and Gray’s method was used to test the cumulative incidence of SREs between the different treatment groups.

Result

In the PSM cohorts, patients in the platinum-based palliative chemotherapy (PCT) + ZA group and PCT alone group achieved similar 3-year OS (57.3% vs. 46.4%; log rank P = 0.188). Multivariate analysis indicated that ZA administration was not an independent prognostic factor (HR, 0.783; 95% CI, 0.267–2.300; P = 0.657). There was no significant difference in acute treatment toxicity between the 2 treatment groups, although the cumulative incidence of bone-related events (SREs) was significantly lower in the PCT + ZA group (Fine-Gray P = 0.026).

Conclusion

ZA combined with PCT could not improve OS in NPC patients with bone-only metastasis at diagnosis. However, the incidence of SREs could be effectively prevented via ZA application.

12 week PET-CT has low positive predictive value for nodal residual disease in human papillomavirus-positive oropharyngeal cancers

23-08-2019 – Robert Rulach, Suyun Zhou, Fraser Hendry, David Stobo, Allan James, Mary-Frances Dempsey, Derek Grose, Carolynn Lamb, Stefano Schipani, Mohammed Rizwanullah, Christina Wilson, Claire Paterson

Journal Article

Objectives

Surveillance PET-CT scans at 12 weeks post-radiotherapy for head and neck cancer can be used to omit neck dissections with no detriment in overall survival. Human Papillomavirus (HPV) driven tumours behave differently on conventional imaging after radiotherapy but it is unknown if this effect is seen on PET-CT and if HPV status affects the accuracy of PET-CT. We aimed to determine the negative and positive predictive values (NPV and PPV) of 12 week surveillance PET-CT in HPV positive and negative tumours, and investigate predictors of relapse in equivocal responders.

Materials and methods

A retrospective cohort study in a UK tertiary level oncology hospital, between 2013 and 2016 included adults with oropharyngeal squamous cell carcinoma, or HPV positive head and neck squamous cell cancers of unknown primary, treated with radiotherapy.

Results

The PPVs of 12 week PET-CT in HPV positive and negative disease are 30% and 81.8% respectively (p < 0.01). The NPVs of 12 week PET-CT in HPV positive and negative disease are 92.9% and 55.6% respectively (p < 0.01). 67% of HPV positive patients with equivocal responses on 12 week PET-CT achieved complete response by 24 weeks. Equivocal responses in HPV positive disease had statistically similar survival to patients with complete responses. Comparing disease and imaging characteristics, there were no predictors of residual tumour.

Conclusions

HPV positive tumours have a poor PPV of 30% on 12 week surveillance PET-CTs and take longer to achieve complete response. A period of further surveillance can be considered instead of an immediate neck dissection in this group of patients.

Identification of markers predictive for response to induction chemotherapy in patients with sinonasal undifferentiated carcinoma

20-08-2019 – Yoko Takahashi, Frederico O. Gleber-Netto, Diana Bell, Dianna Roberts, Tong-Xin Xie, Ahmed S. Abdelmeguid, Curtis Pickering, Jeffrey N. Myers, Ehab Y. Hanna

Journal Article

Objectives

Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Despite aggressive multimodal therapy, its prognosis remains poor. Because of its locally advanced nature and high propensity for distant metastasis, we frequently use induction chemotherapy before definitive therapy in patients with SNUC. However, about 30% of patients do not respond to induction chemotherapy, and lack of response is associated with a poor survival rate. Therefore, in this study, we performed gene expression analysis of SNUC samples to identify prognostic markers for induction chemotherapy response.

Materials and methods

Formalin-fixed, paraffin-embedded SNUC tumor samples from previously untreated patients harvested before induction chemotherapy were used. Gene expression was performed using an oncology gene expression panel.

Results

We identified 34 differentially expressed genes that distinguish the responders from the non-responders. Pathway analysis using these genes revealed alteration of multiple pathways between the two groups. Of these 34 genes, 24 distinguished between these two groups. Additionally, 16 gene pairs were associated with response to induction therapy.

Conclusion

We identified genes predictive of SNUC response to induction chemotherapy and pathways potentially associated with treatment outcome. This is the first report of identification of predictive biomarkers for response of SNUC to induction chemotherapy, and it may help us develop therapeutic strategies to improve the treatment outcomes of non-responders.

Fluorescence molecular imaging for identification of high-grade dysplasia in patients with head and neck cancer

20-08-2019 – Shayan Fakurnejad, Stan van Keulen, Naoki Nishio, Myrthe Engelen, Nynke S. van den Berg, Guolan Lu, Andrew Birkeland, Fred Baik, A. Dimitrios Colevas, Eben L. Rosenthal, Brock A. Martin

Journal Article

Objective

High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium.

Materials and methods

Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry.

Results

11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia.

Conclusion

Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.

Risk-based stratification in head and neck mucosal melanoma

20-08-2019 – Antoine Moya-Plana, David Mangin, Laurent Dercle, Rabah Taouachi, Odile Casiraghi, Samy Ammari, France Nguyen, Stéphane Temam, Caroline Robert, Philippe Gorphe

Journal Article

Background

Head and neck mucosal melanoma (HNMM) is a rare and aggressive disease with a high metastatic potential. Two staging systems are currently available: one specific to HNMM (mm
TNM) and one specific to primary tumour sites (scc
TNM). Our main objective was to assess the prognostic value of both of these classifications in order to allow accurate risk-based classification.

Methods

We performed a retrospective cohort study of patients with HNMM treated consecutively between 2000 and 2017. All of the patients were restaged using the mm
TNM and the scc
TNM. A prognostic analysis was carried out according to both staging systems.

Results

There were 96 patients with an HNMM in our cohort, of whom 80 underwent surgical treatment followed by radiotherapy. The median overall survival (OS) and progression-free survival (PFS) for the operated patients were 39 months (95% CI, 21.6–56.4 months) and 18 months (95% CI, 6.5–29.5 months), respectively. A paranasal sinus localization was associated with lower survival compared to a nasal cavity primary localization (p < 1 0−4). Both of the classifications correlated with OS, PFS, and distant metastasis-free survival. High-risk HNMM were characterized as T4/stage IV by the mm
TNM and T3-4/stage III-IV by the scc
TNM. Given the primary tumour location, both TNM classifications were suitable for risk-stratification of sinonasal mucosal melanomas. However, combining both TNM, we defined new stages mm
T3A and mm
T3B according to scc
TNM with a more accurate risk stratification (p < 1 0−4).

Conclusions

Both of the classifications should be combined, in order to improve the risk-stratification of patients with HNMM.

Comparison of GP and TPF induction chemotherapy for locally advanced nasopharyngeal carcinoma

20-08-2019 – Jinbing Zhu, Baofeng Duan, Huashan Shi, Yan Li, Ping Ai, Jiangfang Tian, Nianyong Chen

Journal Article

Objectives

This study aims to compare two induction chemotherapy regimens, TPF and GP, for patients with locally advanced nasopharyngeal carcinoma (NPC).

Materials and methods

We analyzed patients with newly diagnosed stage III-IVA NPC (excluding T3/T4N0, AJCC) between December 2010 and May 2015 who were treated with TPF or GP induction chemotherapy (IC) followed with concurrent chemoradiotherapy (CCRT) and those treated with CCRT alone. Treatment compliance, survival outcomes and grade 3–4 side effects were compared among these three groups.

Results

A total of 189 patients were eligible for this study, with 87 (46.0%), 71 (37.6%) and 31 (16.4%) in the TPF, GP and CCRT alone groups. All patients were followed for 3 years. There was no difference in the 3-year survival rate between GP- and TPF-treated patients. Disease-free survival (DFS) and overall survival (OS) were significantly improved in both IC groups compared with those in the CCRT alone group. Multivariable analysis suggested that patients with N3 had a higher risk of distant metastasis than those with N1-2. GP is not inferior to TPF regardless of different N categories. There were significant more grade 3–4 treatment-related toxicity in TPF group than in GP group.

Conclusion

Our study found that in locally advanced NPC, the GP induction chemotherapy regimen is equivalent to TPF in treatment outcomes, but with significant less grade 3–4 acute toxicity. Further studies are needed to validate our findings.

Treatment trends in oropharyngeal carcinoma: Surgical technology meets the epidemic

20-08-2019 – T.J. Gal, Jon A. Slezak, Alexandra E. Kejner, Quan Chen, Bin Huang

Journal Article

Objective

To characterize temporal trends in treatment patterns for oropharyngeal carcinoma, and to evaluate the emerging role of surgical therapy in the era of transoral robotic surgery (TORS).

Methods

Patients with oropharynx cancer between 2004 and 2016 identified using the National Cancer Database. Demographics and primary treatment modalities were obtained. Treatment was classified as surgery alone, surgery with radiation/chemotherapy, or primary radiation/chemotherapy. Annual distribution of cases treated by the various modalities was tabulated by site and early (I/II) versus late (III/IV) stage disease (AJCC 7th edition). The “TORS era” was defined as beginning in 2010.

Results

149,534 patients were identified. The majority (56.8%) were treated with radiation ± chemotherapy. 53,069 patients had surgery as part of treatment, 72.6% (N = 38,533) of which received adjuvant therapy. 5293 TORS procedures were performed between 2010 and 2016 with trends away from open and other endoscopic procedures. Despite a 31.0% increase in the number of cases treated surgically from before TORS (2009) to 2016, the percentage of cases treated surgically decreased from 35.0% to 32.7%, with a 44.2% increase in non-surgical therapy. Increases in the percentage of patients treated surgically were observed for base of tongue tumors (24.3–25.2%) and early stage disease (59.9–62.2%).

Conclusion

Despite the increase in the overall number of patients with oropharynx cancer, the percentages of patients treated surgically remains relatively stable. Notable increases were observed for base of tongue tumors and early stage disease.

Postoperative wound infections, neutrophil-to-lymphocyte ratio, and cancer recurrence in patients with oral cavity cancer undergoing surgical resection

20-08-2019 – John R. de Almeida, Christopher M.K.L. Yao, Hedyeh Ziai, Phillip Staibano, Shao Hui Huang, Ali Hosni, Andrew Hope, Scott V. Bratman, Eric Monteiro, Ralph W. Gilbert, Dale H. Brown, Patrick J. Gullane, Jonathan C. Irish, Jie Su, Wei Xu, David P. Goldstein

Journal Article

Background

It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression.

Methods

Patients undergoing surgery for oral cancer from 1998 to 2011 were reviewed. Univariable analyses and multivariable were performed. Propensity scores were used to create matched cohorts for infection and non-infection groups. Neutrophil-to-lymphocyte ratios (NLR) were determined prior to surgery and at the time of infection.

Results

Of 551 patients with oral cancer treated with surgery, 98 developed wound infections (18%). Tumor factors associated with wound infections included higher T and N category, extranodal extension, depth of invasion, lymphovascular and perineural invasion (p < 0.02 for all). On univariable analysis, wound infection was a predictor for recurrence free survival (p < 0.001), locoregional control (p = 0.01), and distant control (p < 0.001). Wound infection was not a predictor of overall survival (p = 0.88), recurrence free survival (p = 0.17), locoregional control (p = 0.79) or distant control (p = 0.18) on multivariable analysis. Using a propensity score matched cohort of 83 patients with and without infection, wound infection was not associated with recurrence free survival (p = 0.21), overall survival (p = 0.71), and locoregional control (p = 0.84), although there was a trend towards increased distant metastases (p = 0.10). Patients with wound infection had a greater preoperative NLR as well as a greater rise in the NLR after surgery, but these were not associated with survival or recurrence.

Conclusions

Patients with wound infections have more adverse pathologic features. However, wound infection was not associated with poorer cancer outcomes although a trend towards increased distant metastases should be investigated.

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer

20-08-2019 – Shawn Iganej, Bryce W. Beard, Jergin Chen, Gary L. Buchschacher, Iman A. Abdalla, Lester D.R. Thompson, Onita Bhattasali

Journal Article

Objective

We compared high-dose cisplatin (HDC) vs. triweekly carboplatin (TC)-based chemoradiation in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Materials and Methods

A retrospective review was conducted from 2006 to 2015 of 421 patients with locally advanced p16-positive OPSCC receiving definitive radiotherapy concurrent with 3 cycles of HDC (100 mg/m2, n = 230) or TC (AUC = 5, n = 191). Three-year locoregional recurrence (LRR), distant metastasis (DM), overall recurrence rate (ORR), overall survival (OS), and cause-specific survival (CSS) are reported. HDC and TC were compared accounting for age, sex, comorbidity index score, smoking history, T stage, and N stage.

Results

For all-comers, no difference was observed between HDC and TC for any outcome except for ORR which was lower in patients receiving HDC (12% vs. 17%, p = 0.03). On stage-based analysis, no difference was observed between agents for any outcome for stage I or II disease. However, patients with stage III disease receiving HDC had lower rates of LRR (9% vs. 21%, p = 0.03), DM (7% vs. 28%, p = 0.006), and ORR (14% vs. 40%, p = 0.002), and superior OS (89% vs. 78%, p = 0.04) and CSS (95% vs. 80%, p = 0.02). Patients receiving HDC experienced higher rates of grade 3 leukopenia (25% vs. 11%, p < 0.001), weight loss ≥20% from baseline (21% vs. 8%, p < 0.001), and gastrostomy-tube placements (66% vs. 27%, p < 0.001).

Conclusion

TC demonstrated comparable outcomes to HDC for stage I or II HPV-associated OPSCC but was inferior to HDC for stage III disease. TC was associated with less toxicity and may be a potential de-intensification agent for early-stage disease.

Impact of dysplastic surgical margins for patients with oral squamous cell carcinoma

20-08-2019 – Tseng-Cheng Chen, Huei-Lun Chang, Tsung-Lin Yang, Pei-Jen Lou, Yih-Leong Chang, Jenq-Yuh Ko, Cheng-Ping Wang

Journal Article

Objectives

Dysplastic changes at the surgical margin of oral squamous cell carcinoma (OSCC) could be encountered frequently. However, the impact of a dysplastic surgical margin on patients with OSCC remains unclear.

Materials and methods

Retrospectively, we reviewed patients with OSCC who were diagnosed and treated at the National Taiwan University Hospital between January 2010 and December 2015. Patients were divided into four groups: clear (≥5 mm), close (<5 mm), positive, and dysplastic margins.

Results

Of 1642 patients, 596 had clear margin, 169 had positive margin, 707 had close margin, and 170 had dysplastic margin. The mean age at diagnosis was 55 ± 11 years (range, 16-97 years). Dysplastic margins were frequently present in patients with primary T1/T2 OSCC (odds ratio OR = 1.7, p = 0.009), tumor without perineural invasion (OR = 1.48, p = 0.04), and tumor thickness ≤10 mm (OR = 1.94, p = 0.001). In patients with clear, close, positive, and dysplastic margins, the 5-year disease-free survival rates were 63.1%, 51%, 37.2%, and 54.7%, respectively; overall survival (OS) rates were 71.1%, 61.9%, 49%, and 72%, respectively. Disease-free and overall survival were not significantly different in patients with dysplastic and clear margins (p = 0.37 and p = 0.38, respectively). Adjuvant radiotherapy had no significant benefit for patients with dysplastic margins. Finally, a multivariate analysis showed that the presence of a dysplastic margin was not an independent risk factor for disease-free (p = 0.43) and overall survival (p = 0.71).

Conclusions

The survival rates of the patients with OSCC who had dysplastic margin were significantly better than those with positive margin.

Liquid biopsy in head and neck squamous cell carcinoma: Prognostic significance of circulating tumor cells and circulating tumor DNA. A systematic review

20-08-2019 – Dorina Lauritano, Luca Oberti, Federica Gabrione, Alberta Lucchese, Massimo Petruzzi, Francesco Carinci, Lorenzo Lo Muzio

Journal Article, Review

Accuracy of computer-assisted mandibular reconstructions with free fibula flap: Results of a single-center series

21-08-2019 – Femke Goormans, Yi Sun, Michel Bila, Joseph Schoenaers, Joris Geusens, Heinz-Theo Lübbers, Wim Coucke, Constantinus Politis

Journal Article

Objectives

We evaluated the accuracy of computer-assisted mandibular reconstructions.

Patients and methods

We retrospectively reviewed data for 26 patients who had mandibular reconstruction with a microvascular free fibula flap, January 2015 to June 2018. Postoperative mandible models were obtained from computed tomography scans. After registering the models to the corresponding preoperative plan, we performed comparative measurements. Patients were grouped by condylar involvement and subdivided based on number of fibular segments used for reconstruction. For each segment, we measured length and osteotomy angles. For the final postoperative outcome, we compared intercoronoid, intergonial, and anteroposterior distances and intersegmental plane shift.

Results

Means (SD) for deviation of each osteotomy angle and fibular segment length were 1.98° (2.98) and 1.78 mm (2.69), respectively, remaining constant across subgroups. Other mean values were as follows: intercoronoid distance deviation, 3.86 mm (range, 0.20–11.21 mm); intergonial distance deviation, 3.14 mm (range, 0.05–8.28 mm); anteroposterior distance deviation, 2.92 mm (range, 0.03–8.49 mm); and intersegmental plane shift, 11.00° (range, 2.76–24.15°). Where the condyle was preserved, the intercoronoid and intergonial deviation means differed significantly (respectively 5.02 mm and 4.88 mm, both P < 0.05) for one-segmented and three-segmented fibular reconstructions. Furthermore, reconstructions involving the condylar region compared with condyle preservation showed significantly different intersegmental plane shifts (7.18°; P < 0.05).

Conclusion

Computer-assisted surgery provides cutting guides for obtaining accurate fibular segments, but current fixation methods lead to inaccuracies and reproducibility errors. In multisegmental transfer with condylar involvement, computer-assisted fixation is recommended to ensure accuracy of the preoperative plan.

Exploring the role of Mir204/211 in HNSCC by the combination of bioinformatic analysis of ceRNA and transcription factor regulation

20-08-2019 – Jingyi Cai, Yeke Yu, Yuzi Xu, Hao Liu, Jiawei Shou, Liangkun You, Hanliang Jiang, XuFeng Han, Binbin Xie, Weidong Han

Journal Article

Objectives

This study aimed to reveal the regulatory roles of micro
RNAs in head and neck squamous cell carcinoma (HNSCC) through comprehensive ce
RNA, mi
RNA-transcription factor (TF)-hub gene network and survival analysis.

Materials and methods

Expression analysis was performed using the edge
R package based on The Cancer Genome Atlas database. The ce
RNA network was screened by intersecting prediction results from mi
Rcode, mi
RTar
Base, mi
RDB and Target
Scan. GSE30784, GSE59102 and GSE107591 from the Gene Expression Omnibus repository were chosen for cross-validation. Hub genes were identified using a protein-protein interaction network constructed by Search Tool for the Retrieval of Interacting Genes. The Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TTRUST) was utilized to map the mi
RNA-TF-Hub gene network. Patient overall survival was analyzed using the ‘survival’ package in R. Structural and functional analysis of mi
R-204/211 was based on mi
Rbase and RNAstructure.

Results

A ce
RNA network of 178 lnc
RNAs, 19 mi
RNAs and 55 m
RNAs was generated, and a TF regulatory network with 11 mi
RNAs, 11 TFs and 18 hub genes was constructed from the 52 hub genes identified through the protein–protein interaction (PPI) network. Survival analysis demonstrated that the dysregulated expression of 11 lnc
RNAs and 14 m
RNAs was highly related to overall survival. Furthermore, mi
R-204 and mi
R-211 were significantly involved in the network with identical mature structures, indicating them as key mi
RNAs in HNSCC.

Conclusion

This study reveals the comprehensive molecular regulatory networks centralized by mi
RNAs in HNSCC and uncovers the crucial role of mi
R-204 and mi
R-211, which may become potential diagnostic and therapeutic targets.

The effect of time between diagnosis and initiation of treatment on outcomes in patients with head and neck squamous cell carcinoma

20-08-2019 – Luke H. DeGraaff, Alexis J. Platek, Austin J. Iovoli, Kimberly E. Wooten, Hassan Arshad, Vishal Gupta, Ryan P. McSpadden, Moni Abraham Kuriakose, Wesley L. Hicks, Mary E. Platek, Anurag K. Singh

Journal Article

Objectives

To quantify the effect that time to initiation of treatment after diagnosis has on the outcomes of patients with head and neck squamous cell carcinoma (HNSCC).

Methods

This is a single institution retrospective analysis of 633 HNSCC patients treated from 2004 to 2017. Clinical information was abstracted from the medical records. Patients were divided into quartiles based on the time to treatment initiation (0–27 days, 28–41 days, 42–60 days, and >60 days). Kaplan-Meier overall survival (OS) curves and multivariate cox proportional hazard ratios were determined for time to treatment quartiles.

Results

Differences in Kaplan-Meier estimates for OS based on treatment time quartiles were statistically significantly (p = 0.02), and multivariate Cox Proportional hazard ratios for OS revealed that patients in the 42–60 day treatment time group had better OS (hazard ratio = 0.55) compared to patients treated >days after diagnosis (p < 0.01).

Conclusions

For our study population, increased time to initiation of treatment did not impact overall survival. These results may help to alleviate patient anxiety while allowing time for useful interventions such as smoking cessation, nutritional counseling, and others that can affect clinical outcomes.

APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma

20-08-2019 – Daniel L. Faden, Fei Ding, Yan Lin, Shuyan Zhai, Fengshen Kuo, Timothy A. Chan, Luc G. Morris, Robert L. Ferris

Journal Article

HNSCC is an immunologically active tumor with high levels of immune cell infiltration, high mutational burden and a subset of patients who respond to immunotherapy. One of the primary sources of mutations in HNSCC is the cytidine deaminase APOBEC3, which is a known participant in innate immunity. Why particular HNSCCs have higher rates of APOBEC mutations and how these mutations relate to the immune microenvironment remains unknown.

Utilizing whole exome and RNA-Seq datasets from TCGA HNSCCs we annotated APOBEC mutations, immune cell populations, activating and end effectors of immunity and neoantigens in order to interrogate the relationship between APOBEC mutations and the immune landscape.

Immune cell populations and composite scores of immune activation were tightly associated with APOBEC mutational burden (p = 0.04–1.17e-5). HNSCC had the highest levels of IFNy across cancer types with high APOBEC mutational burden, with the highest IFNy scores in HPV mediated HNSCC. Tumor specific neoantigens were significantly correlated with APOBEC mutational burden while other sources of neoantigens were not (0.53 0.24, 0.76 p = 8e-5). The presence of a germline APOBEC polymorphism was more prevalent in non-white, non-black patients and within this group, patients with the polymorphism had higher APOBEC mutational burden (p = 0.002).

APOBEC mutations are tightly linked to immune activation and infiltration in HNSCC. Multiple mechanisms may exist within HNSCC leading to APOBEC mutations including immune upregulation in response to neoantigens and viral infection, via induction of IFNy. These mechanisms may be additive and not mutually exclusive, which could explain higher levels of APOBEC mutations in HPV mediated HNSCC.

pDC depletion induced by CD317 blockade drives the antitumor immune response in head and neck squamous cell carcinoma

20-08-2019 – Lei-Lei Yang, Liang Mao, Hao Wu, Lei Chen, Wei-Wei Deng, Yao Xiao, Hao Li, Lu Zhang, Zhi-Jun Sun

Journal Article

Objectives

Dysregulation of immune cells in the tumor microenvironment is a hallmark of head and neck squamous cell carcinoma (HNSCC). Increased infiltration of p
DCs has been reported in the microenvironment of HNSCC. However, the precise immunological role of p
DC and the therapeutic effects of p
DC depletion in HNSCC need to be further investigated.

Materials and methods

CD317 antibodies were applied for depleting p
DCs in an immunocompetent transgenic HNSCC mouse model. Tumor volume was monitored. Flow cytometric analysis was conducted for studying the immune profile changes after p
DC depletion. In addition, immunohistochemical staining was carried out in a human HNSCC tissue microarray for detecting the infiltration of p
DCs. We also analyzed the survival implication of p
DCs and its correlation with other immune related markers in human HNSCC.

Results

p
DC depletion in the transgenic HNSCC mouse model significantly delayed tumor growth. After p
DCs were depleted, T cells were markedly revitalized, and the proportions of regulatory T cells (Tregs) and monocytic myeloid-derived suppressor cells (MDSCs) were decreased. In human HNSCC microenvironment, p
DC infiltration was upregulated and its high infiltration conferred a poor prognosis. Moreover, p
DC infiltration was closely correlated with the expression of Foxp-3, PD-1, TIM-3, and LAG-3.

Conclusion

Our findings demonstrated that p
DCs play a negative immunomodulatory role in HNSCC and may present as a target for effective immunotherapy.

Non-invasive screening of a microRNA-based dysregulation signature in oral cancer and oral potentially malignant disorders

20-08-2019 – T. Yap, C. Seers, K. Koo, L. Cheng, L.J. Vella, A.F. Hill, E. Reynolds, A. Nastri, N. Cirillo, M. McCullough

Journal Article

Introduction

We have previously shown that oral swirls are a robust source of micro
RNA protected by extracellular vesicles, potentially useful to detect oral squamous cell carcinoma (OSCC)-associated molecular aberration.

Objectives

To study a developed dysregulation score and risk classification algorithm based upon a panel of OSCC-associated micro
RNA in oral swirls from individuals with OSCC and oral potentially malignant disorders (OPMDs).

Materials and methods

An OSCC-associated panel of 5 micro
RNAs (mi
R-24; mi
R-21; mi
R-99a; let-7c; mi
R-100;) was quantified by q
PCR in 190 individuals with and without mucosal abnormalities, including OSCC (n = 53) and OPMDs (n = 74). Each sample was analyzed using a developed dysregulation score (d
SCORE) and risk classification algorithm, allocating a LOW- or HIGH-RISK score. The influence of demographic, systemic, oral health and mucosal disease factors on the developed test was analyzed.

Results

Micro
RNA for analysis can be predictably isolated from oral swirls sourced from individuals with a range of demographic, systemic and oral health findings. Utilizing the presence of HIGH-RISK identified OSCC patients with 86.8% sensitivity and 81.5% specificity. Older age and female gender were associated with higher d
SCOREs and higher proportions of HIGH-RISK classification amongst individuals with no mucosal abnormalities. The d
SCOREs for all subgroups of OPMDs were significantly different from the OSCC group.

Conclusion

This is the first comparison of micro
RNA sourced from oral swirls from individuals with OPMDs with individuals with and without OSCC. A HIGH-RISK dysregulation signature was found to be accurate in indicating the presence of OSCC and exampled to parallel malignant transformation.

Health-related quality of life of patients treated with chemoradiotherapy plus or minus prophylactic antibiotics to reduce the number of pneumonias for locally advanced head and neck cancer, the PANTAP study

20-08-2019 – Janneke C. Ham, Carla M.L. van Herpen, Chantal M.L. Driessen, Winette T.A. van der Graaf, Olga Husson

Journal Article

Objectives

The recent PANTAP trial showed that administration of prophylactic antibiotics in locally advanced head and neck carcinoma (LAHNC) patients treated with chemoradiotherapy reduced fever, hospitalization and costs. The current study describes the effect of prophylactic antibiotics on health-related quality of life (HRQoL), another secondary endpoint of the trial.

Materials and methods

In this multicenter randomized trial, LAHNC patients treated with chemoradiotherapy received prophylactic antibiotics or standard care. HRQoL was assessed at baseline (before chemoradiotherapy), day 28 of chemoradiotherapy (one day before starting prophylactic antibiotics), the final day of radiotherapy, and 3.5 months after the end of chemoradiotherapy, using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC H&N35 module, and the Performance Status Scale for Head & Neck cancer patients (PSS-HN).

Results

Ninety-five patients were randomized: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. Thirty-four patients in the standard group (70.8%) and 28 patients in the prophylaxis group (59.6%) completed the questionnaires at baseline and at follow-up. No significant differences in HRQoL were found at baseline and at day 28. At the end of radiotherapy, the prophylaxis group performed better on almost all functional subscales of the EORTC QLQ-C30 and reported less symptoms. At the end of follow up, almost no differences were seen between the two treatment groups.

Conclusion

Prophylactic antibiotics during chemoradiotherapy for LAHNC patients improved HRQoL at the end of the radiotherapy, however no differences were found 3.5 months after the end of chemoradiotherapy.

Elective neck dissection for salvage laryngectomy: A systematic review and meta-analysis

20-08-2019 – Chen Lin, Sidharth V. Puram, Mustafa G. Bulbul, Rosh K. Sethi, James W. Rocco, Matthew O. Old, Stephen Y. Kang

Journal Article

Objective

Elective neck dissection (END) for salvage laryngectomy remains controversial due to variability in reported occult nodal metastasis rates and postoperative complications. We performed a meta-analysis to examine the role of END for treatment of the clinically N0 (c
N0) neck in the salvage setting.

Methods

A PubMed search, without limit on years searched, was conducted for English language articles. Additional sources were found by reviewing bibliographies of pertinent articles. Studies had to include END data for salvage laryngectomy for locally recurrent squamous cell carcinoma of the larynx with clinically negative regional metastasis. For patients who underwent END, pathological node status had to be reported. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Data were pooled using a random-effects model.

Results

Nineteen studies were included in the analysis. Within the END group, 31% were supraglottic, 61% were glottic, 6% were transglottic, and 1% were subglottic. The pooled rate of occult nodal metastasis was 14% (95% CI = 0.11–0.17) for all subsites. In subsite-specific analyses, occult nodal metastasis rates were 24% for supraglottic, 9% for glottic, and 17% for transglottic recurrences. Occult nodal metastasis was higher in recurrent T3/4 tumors (21%) compared to recurrent T1/2 tumors (9%) (relative risk (RR) = 2.17, 95% CI = 1.23–3.63, p = 0.003). The RR of postoperative complications with END compared to observation was 1.72 (95% CI = 0.96–3.10, p = 0.07).

Conclusions

The highest rates of occult nodal metastasis are associated with supraglottic recurrence and recurrent T3/T4 tumors. These data should be considered when deciding whether to perform END for salvage laryngectomy.

Value of diffusion MR imaging in differentiation of recurrent head and neck malignancies from post treatment changes

20-08-2019 – Ankush Jajodia, Deepa Aggarwal, Arvind K. Chaturvedi, Avinash Rao, Vivek Mahawar, Munish Gairola, Mudit Agarwal, Sumit Goyal, Venkata Pradeep Babu Koyyala, Sunil Pasricha, Rupal Tripathi

Journal Article

Purpose

Role of diffusion-weighted (DW) MR imaging in differentiating residual or recurrent neck malignancies from postoperative/post-radiation changes with histopathological correlation and comparison with PET-CT.

Methods and materials

Prospective observational study for a period of 1 year in 62 post-radiation/post-operative patients suspected to have residual/recurrent tumors of neck with lesion diameter more than 5 mm measured on MRI.

Results

Mean ADC for recurrent/residual tumors: 1.008 ± 0.220 × 10−3 mm2/s – significantly lower than mean ADC value for post-treatment changes of 1.69 ± 0.40 × 10−3 mm2/s (p < 0.0001). The overall diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the qualitative assessment for the use of DWI in differentiating tumors recurrence from post-treatment changes were 96.6%, 96% and 83.3%, respectively. Upon quantitative analysis of the DW imaging data, a threshold ADC value of 1.3 × 10−3 mm2/s used for differentiating between post-treatment changes and recurrent cancers showed the highest combined sensitivity of 94%, specificity of 83.3%, accuracy of 93.6%, positive predictive value of 95.9%, and negative predictive value of 83.3%.

Conclusion

DW MRI is a promising non-invasive MRI technique used to differentiate recurrent/residual head and neck malignancies from posttreatment changes based on ADC values. DWI offers advantage as it has a short scanning time and can be safely added to standard MRI protocol with minimum patient discomfort. Complementary use of DWI and PET/CT imaging may increase diagnostic confidence for differentiating recurrent disease from radiation therapy-induced changes after 6–12 months in posttreatment cases.

Immune profiles in primary squamous cell carcinoma of the head and neck

20-08-2019 – Vassiliki Saloura, Evgeny Izumchenko, Zhixiang Zuo, Riyue Bao, Michael Korzinkin, Ivan Ozerov, Alex Zhavoronkov, David Sidransky, Atul Bedi, Mohammad O. Hoque, Hartmut Koeppen, Michaela K. Keck, Arun Khattri, Nyall London, Nikita Kotlov, Aiman Fatima, Theodore Vougiouklakis, Yusuke Nakamura, Mark Lingen, Nishant Agrawal

Journal Article

Objectives

In this study we describe the tumor microenvironment, the signaling pathways and genetic alterations associated with the presence or absence of CD8+ T-cell infiltration in primary squamous cell carcinoma of the head and neck (SCCHN) tumors.

Materials and Methods

Two SCCHN multi-analyte cohorts were utilized, the Cancer Genome Atlas (TCGA) and the Chicago Head and Neck Genomics (CHGC) cohort. A well-established chemokine signature classified SCCHN tumors into high and low CD8+ T-cell inflamed phenotypes (TCIP-H, TCIP-L respectively). Gene set enrichment and i
PANDA analyses were conducted to dissect differences in signaling pathways, somatic mutations and copy number aberrations for TCIP-H versus TCIP-L tumors, stratified by HPV status.

Results

TCIP-H SCCHN tumors were enriched in multiple immune checkpoints irrespective of HPV-status. HPV-positive tumors were enriched in markers of T-regulatory cells (Tregs) and HPV-negative tumors in protumorigenic M2 macrophages. TCIP-L SCCHN tumors were enriched for the β-catenin/WNT and Hedgehog signaling pathways, had frequent mutations in NSD1, amplifications in EGFR and YAP1, as well as CDKN2A deletions. TCIP-H SCCHN tumors were associated with the MAPK/ERK, JAK/STAT and m
TOR/AKT signaling pathways, and were enriched in CASP8, EP300, EPHA2, HRAS mutations, CD274, PDCD1LG2, JAK2 amplifications.

Conclusions

Our findings support that combinatorial immune checkpoint blockade and depletion strategies targeting Tregs in HPV-positive and M2 macrophages in HPV-negative tumors may lead to improved antitumor immune responses in patients with TCIP-H SCCHN. We highlight novel pathways and genetic events that may serve as candidate biomarkers and novel targeted therapies to enhance the efficacy of immunotherapy in SCCHN patients.

Beavertail modification of the radial forearm free flap in total oral glossectomy reconstruction: Technique and functional outcomes

20-08-2019 – Peter T. Dziegielewski, Jana Rieger, Mohamed A. Shama, Daniel A. OConnell, Jeffrey R. Harris, Hadi Seikaly

Journal Article

Objective

The total oral tongue (anterior 2/3 glossectomy) defect is seldom addressed in the literature. This is the first series to describe a consistent technique for its reconstruction. The aim of the study is to describe the use of the beavertail modified radial forearm free flap (BTRFFF) to reconstruct a total oral tongue defect and the functional and quality of life outcomes associated with it.

Study design

Retrospective review of prospectively collected data from 2000 to 2010.

Methods

All patients at the University of Alberta undergoing head and neck free flap surgery are enrolled in a prospective functional outcomes program. Pre-operatively and at set post-operative time points patients complete videofluoroscopic swallowing studies (VFSS), speech evaluations and quality of life questionnaires (EORTC H&N-35). Peri-operative outcomes were also measured.

Results

17 consecutive patients were included. All were gastrostomy tube free at 12 months post-operatively and tolerating a full soft diet with aspiration scores of 0. Swallowing transit times increased by a mean of 0.4 s (p = 0.32). Speech intelligibility remained high with mean sentence intelligibility at 75% and single word intelligibility at 62%. Quality of life scores returned to baseline and remained satisfactory. Complications related to the BTRFFF were limited to scarring.

Conclusions

The BTRFFF provides a robust reconstructive option for the total oral tongue defect with excellent long term functional outcomes and quality of life.

Transoral 980-nm/1470-nm dual-wavelength fiber laser microsurgery for early-stage glottic carcinoma

20-08-2019 – Faya Liang, Zhiwen Xiao, Renhui Chen, Pin Han, Peiliang Lin, Yuzhang Huang, Xiaoming Huang

Journal Article

Objectives

To investigate the effective and safety of transoral 980-nm/1470-nm dual-wavelength fiber laser microsurgery for early-stage glottic carcinoma by compared with CO2 laser surgery.

Materials and Methods

From September 2015 to July 2018, 44 patients with early glottic carcinoma underwent transoral microsurgery were divided into 980-nm/1470-nm dual-wavelength fiber laser surgery (Dual-wavelength fiber laser group) and CO2 laser surgery (CO2 laser group). The operative time, number of other hemostatic devices used, postoperative blood loss, surgical complications and postoperative length of hospital stay The time of mucosal epithelialization and Voice Handicap Index-10(VHI-10) in pre-operation, 1-month postoperation and 6-month postoperation in both two groupswere retrospectively analyzed.

Results

All the patients underwent successful operation and all the tumors received en-bloc resection with negative margins. The median operative time in Dual-wavelength laser group was faster than CO2 laser group (32.00 min vs 37.50 min, p = 0.014). There was no statistically significant difference between the two groups in the median postoperative hospital stay and the median time of mucosal epithelialization. No patient need feeding tubes place temporarily or permanently in both two groups. Tongue numbness, tear of the palatal arch, postoperative vocal cord adhesion, VHI-10 score in Pre-operation, 1-month postoperation and 6-month postoperation were similar in both two group. No recurrence was reported in both groups during follow-up.

Conclusion

Compared to the CO2 laser surgery, transoral 980-nm/1470-nm dual-wavelength fiber laser microsurgery is a safe and feasible procedure for early-stage glottic carcinoma. It can provide clearer surgical field without hemorrhage and make the operation simpler, smoother and faster.

Treatment for oral squamous cell carcinoma: Impact of surgeon volume on survival

20-08-2019 – Timothy Liu, Michael David, Owen Ellis, Tsu-Hui (Hubert) Low, Carsten E. Palme, Jonathan Clark, Martin Batstone

Journal Article

Background

The volume-outcome relationship is a well-known phenomenon in surgical oncology. The aim of this study was to quantify the impact of surgeon volume on the treatment outcome of oral squamous cell carcinoma (OSCC) patients.

Methods

All new OSCC cases treated with curative intent between 2008 and 2013 were included. A heterogeneous set of predictor variables was collected, including patient, tumour and treatment factors. The outcomes of interest were recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). To investigate the cut-off in surgeon volume, the number of OSCC resections was analysed in multiplies of 5 cases per annum according to DSS, using univariable regression analysis.

Results

534 cases were recruited. Independently, the negative predictors for patient survival were age, perineural invasion, worsening tumour staging, and extracapsular spread. High-volume surgeon was determined to be most significant at 20 cases per annum and significantly associated with improved RFS (HR: 0.67), OS (HR: 0.44), and DSS (HR: 0.39).

Conclusions

Results from this study support the rationalisation of OSCC management at high-volume centres and in the hands of experienced surgeons for better patient survival. Head and neck surgeons should perform a minimum of 20 OSCC cases per year to maintain competency in OSCC ablation.

Exome sequencing of oral leukoplakia and oral squamous cell carcinoma implicates DNA damage repair gene defects in malignant transformation

20-08-2019 – Camile S. Farah, Maryam Jessri, Nigel C. Bennett, Andrew J. Dalley, Kate D. Shearston, Simon A. Fox

Journal Article

Objectives

To map the genomic pathways of patients with oral leukoplakia (OLK) which transformed to cancer (progressive) and those which did not (non-progressive), and to compare their exomic profiles.

Materials and methods

Whole exome sequencing was performed on 42 sequential samples from five progressive and eight non-progressive patients. Association of genomic variant frequencies with progression or lesion severity were analysed by non-parametric tests (Kruskal-Wallis and Mann-Whitney-Wilcoxon) and multivariate sparse partial least squares discriminant analysis (s
PLS-DA). Enrichment analysis was used to characterise the effect of mutations upon biological pathways. Confirmatory studies used q
PCR and immunohistochemistry.

Results

Using s
PLS-DA, the variant frequency of a small number of genes could be used to classify the samples based on lesion severity or progressive status. Enrichment analysis showed that DNA damage repair gene related pathways were highly impacted in lesions which progressed to cancer. Multivariate analysis of a set of 148 DNA damage repair genes could be used to classify progressive lesions using mutation frequency. BRCA1, BRCA2 and other double strand break (DSB) repair Fanconi anaemia (FA)/BRCA pathway genes were prominent contributors to this classification.

Conclusion

Patients with progressive and non-progressive OLK can be differentiated using the frequency of exomic variants, particularly in DNA damage repair pathway genes. To our knowledge, this is the first report of FA/BRCA (DSB) pathway involvement in malignant transformation of OLK to oral squamous cell carcinoma (OSCC).

Role of integrin β1 as a biomarker of stemness in head and neck squamous cell carcinoma

20-08-2019 – Jung Hwa Moon, Young Soo Rho, Sang Hyuk Lee, Bon Seok Koo, Hyun Joo Lee, Sung Im Do, Jae Hoon Cho, Young Gyu Eun, Min Woo Park, Hyang Ae Shin, Young Chang Lim

Journal Article

Objectives

Signaling between cancer stem cells (CSC) and their extracellular matrix has a crucial role in CSC progression and maintenance. However, mediators of this signaling pathway in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Here, we explored whether integrin β1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells.

Materials and methods

We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin β1 in primary HNSCC cells. In addition, we studied the role of focal adhesion kinase (FAK), an intracellular downstream molecule of integrin signaling, in influencing stemness of HNSCC. The relevance of Notch1 and integrin β1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin β1 and Notch1 in the samples from HNSCC patients correlated with their survival.

Results

Targeting integrin β1 in HNSCC cells inhibited self-renewal, chemoresistance, and in vivo tumor-forming capacity. Treatment with an inhibitor of FAK decreased self-renewal capacities and expression of various putative stem cell markers (Oct4, Sox2, and Nanog) in a dose-dependent manner. Moreover, knockdown of integrin β1 decreased the expression of Notch1 and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin β1 and Notch1 in their tissue samples had significantly worse survival rate.

Conclusion

Integrin β1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.

Clinical benefits from endoscopy screening of esophageal second primary tumor for head and neck cancer patients: Analysis of a hospital-based registry

20-08-2019 – Chen-Shuan Chung, Wu-Chia Lo, Kuan-Chih Chen, Cheng-Lu Lin, Ming-Hsun Wen, Chen-Hsi Hsieh, Shih-Chiang Lin, Li-Jen Liao

Journal Article

Objectives

Esophageal second primary tumors (SPTs) in head and neck cancer (HNC) patients is not uncommon. The impact of image-enhanced endoscopy (IEE) screening for esophageal SPT on the outcome of HNC patients has not been well clarified.

Methods and methods

Patients with malignancies of the head and neck region and esophagus were recruited from a hospital-based cancer registry between July 2000–December 2016. IEE screening included magnifying endoscopy with narrow-band imaging and chromoendoscopy with Lugols solution. Biopsied specimens with revised Vienna classification categories 1 and 2 were defined as group I, and those with categories 3 to 5 were defined as group II. The Kaplan-Meier estimate and Cox regression model were used for survival analysis.

Results

Totally 1577 HNC and 501 esophageal cancer patients were enrolled. The 5-year overall survival (OS) rates of stage I/II HNC, stage III/IV HNC and esophageal cancer patients were 58%, 29%, and 8%, respectively (p < 0.01). The 5-year OS rate of HNC patients with negative IEE results was higher than that of HNC patients without IEE screening, followed by IEE screening groups I, II and esophageal cancer patients (44% vs. 39% vs. 35% vs. 11% vs. 8%, respectively, p for trend <0.01). Among advanced HNC patients, those who received IEE screening had a trend of better prognosis than those without screening (5-year OS rate of 31% vs. 28%, p = 0.17).

Conclusions

IEE screening for esophageal SPTs is helpful in risk stratification and prognosis prediction for HNC patients. Routine IEE screening is recommended in HNC patients.

Direct medical cost of oropharyngeal cancer among patients insured by Medicaid in Texas

20-08-2019 – Bo Zhao, Shuangshuang Fu, Chi-Fang Wu, Kristina R. Dahlstrom, Joël Fokom Domgue, Samantha Tam, Li Xu, Erich M. Sturgis, David R. Lairson

Journal Article

Objectives

The aim of this study was to estimate the direct 2-year mean incremental medical care costs for incident oropharyngeal cancer (OPC) from the perspective of the Texas Medicaid program.

Methods

OPC patients treated from 2008 to 2012 were selected in the Texas Medicaid database. Using a two-step 1:1 propensity score matching method, we selected controls to determine the differential cost associated with OPC. Monthly and yearly direct costs were estimated for 2 years after the cancer diagnosis. For patients without 2-year complete follow-up, a generalized linear model with gamma distribution and log link function was applied to predict costs for the censored months.

Results

A total of 352 patients with OPC and the same number of controls were included in the study. Among OPC patients, 204 (58%) were covered by Medicaid and Medicare, and 148 patients (42%) were insured under Medicaid only. The adjusted first- and second-year mean differential costs were $45,102 and $11,684 for Medicaid-only enrollees and $5734 and $2162 for Medicaid-Medicare dual-eligible enrollees, respectively. Being male, Hispanic, Medicaid-only eligible, living in the Harlingen region, and having more comorbidities were positively associated with monthly cost. Lubbock residents experienced lower costs.

Conclusions

The direct incremental medical costs associated with OPCs among patients insured by Texas Medicaid were substantial in the first 2 years after cancer diagnosis and should be considered in assessing the economic consequences of increasing the investment in HPV vaccination in Texas.

Sequential alterations of Stensen’s duct and parotid gland after radical surgeries in buccal cancer

20-08-2019 – Shih-Lung Chen, Shy-Chyi Chin, Chi-Kuang Young, Huei-Tzu Chien, Chun-Ta Liao, Chung-Kang Tsao, Chung-Jan Kang, Shiang-Fu Huang

Journal Article

Objectives

The marsupialization of Stensens duct after buccal cancer excision and free flap reconstruction has seldom been reported. In this study, we evaluated the alteration in Stensens duct and parotid gland, without marsupialization or relocation, between the time of surgery and 24 months postoperatively to determine whether ductal management is needed in patients with buccal squamous cell carcinoma (BSCC).

Methods

Eighty-five patients with BSCC receiving primary radical surgery and free flap reconstruction were recruited. Alterations in Stensens duct and parotid gland were assessed by computed tomography during the postoperative period.

Results

The 81 males and 4 females enrolled in study had a tumor status of c
T2 (n = 52, 61%) or c
T3 (n = 33, 39%). In total, 52 (61%) patients received surgery alone, and 33 (39%) received adjuvant concurrent chemoradiotherapy (CCRT) postoperatively. Stensens duct on the affected side was significantly dilated compared to the non-affected side (p < 0.001). The difference in diameter of Stensens duct between the surgery plus CCRT group and the surgery alone group was not significant (p > 0.05), indicating that changes in parotid gland occurred mainly due to surgery. In both the surgery and surgery plus CCRT groups, inflammation of parotid gland had regressed by 24 months.

Conclusions

Stensens duct in BSCC dilatation peaked in the 3rd month after surgery. Changes in parotid gland on the surgically treated side regressed into fatty change by 24 months after surgery.

Nivolumab versus investigator’s choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age

20-08-2019 – Nabil F. Saba, George Blumenschein, Joel Guigay, Lisa Licitra, Jerome Fayette, Kevin J. Harrington, Naomi Kiyota, Maura L. Gillison, Robert L. Ferris, Vijayvel Jayaprakash, Li Li, Peter Brossart

Journal Article

Objectives

Many patients with squamous cell carcinoma of the head and neck (SCCHN) are ≥65 years old; comorbidities and other age-related factors may affect their ability to tolerate traditional chemotherapy. Nivolumab is the only immunotherapy to significantly improve overall survival (OS) versus investigator’s choice (IC) of single-agent chemotherapy at primary analysis in a phase 3 trial (Check
Mate 141) in patients with recurrent/metastatic SCCHN post-platinum therapy. In this post hoc analysis, we report efficacy and safety by age.

Patients and methods

Eligible patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks (n = 240) or IC (methotrexate, docetaxel, or cetuximab n = 121). The primary endpoint of the trial was OS. For this analysis, outcomes were analyzed by age < 65 and ≥65 years. The data cut-off date was September 2017 (minimum follow-up 24.2 months).

Results

At baseline, 68 patients (28.3%) receiving nivolumab and 45 patients (37.2%) receiving IC were ≥65 years. Baseline characteristics were generally similar across age groups. OS and tumor response benefits with nivolumab versus IC were maintained regardless of age. The 30-month OS rates of 11.2% (<65 years) and 13.0% (≥65 years) with nivolumab were more than tripled versus corresponding IC rates of 1.4% and 3.3%, respectively. The nivolumab arm had a lower rate of treatment-related adverse events versus IC regardless of age, consistent with the overall patient population.

Conclusion

In Check
Mate 141, nivolumab resulted in a higher survival versus IC in patients <65 and ≥65 years, with a manageable safety profile in both age groups.

Clinical
Trials.gov: NCT02105636.

Comorbidity in HPV+ and HPV− oropharyngeal cancer patients: A population-based, case-control study

20-08-2019 – Christian Grønhøj, Kathrine Kronberg Jakobsen, Eva Kjær, Jeppe Friborg, Christian von Buchwald

Journal Article

Objectives: Comorbid conditions impact outcome for patients treated for oropharyngeal squamous cell carcinoma (OPSCC) and serve as competing risk factors for death. The purpose of this study was to examine differences in comorbidities in patients with OPSCC and known HPV-DNA.

Material and methods: We included patients diagnosed with OPSCC in Eastern Denmark in 2000–2014. Patients were linked to the Danish National Patient Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at time of diagnosis and following cancer treatment. Patients were age-and sex-matched in a 1:10 ratio with a reference group and stratified according to HPV-status.

Results: In total 1,499 patients (55.0% HPV+) and 14,990 controls were included. Significantly more HPV+ patients had no comorbidities compared to HPV− patients at time of diagnosis (RR: 1.5 (1.3;1.6), n = HPV+: 522, HPV−: 302) and following treatment (RR 1.5 (1.4;1.6), n = HPV+: 342, HPV−: 142). Most prevalent comorbidity was malignancy not including OPSCCs. HPV+ patients had an increased risk of having AIDS before their OPSCC diagnosis compared to the reference population (OR: 4.8 (1.8;12.9)). HPV− patients had increased risk of multiple comorbidities including cerebrovascular disease (OR: 1.9 (1.4;2.5)), peripheral vascular disease (OR: 1.7 (1.9;3.7)), dementia (OR: 2.9 (1.4;5.8)), ulcer disease (OR: 2.6 (1.9;3.5)), liver disease, mild (OR: 9.5 (7.0;13.0)) and severe (OR: 13.9 (5.8;22.8)).

Conclusion: This study showed that HPV− patients had more comorbidities than HPV+ patients at the diagnosis time and following treatment. Irrespective of HPV-status, OPSCC patients had a significant increased risk of (secondary) malignancy compared to the reference population.

Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis

20-08-2019 – Miguel Ángel González-Moles, Isabel Ruiz-Ávila, Lucía González-Ruiz, Ángela Ayén, José Antonio Gil-Montoya, Pablo Ramos-García

Journal Article, Review

Objectives

To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development.

Material and methods

We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses.

Results

Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84–1.49), 1.88% for OLLs (95% CI = 0.15–4.95) and 1.71% for LRs (95% CI = 0.00–5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21–2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40–6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28–3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14–4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98–20.22, p = 0.053).

Conclusions

The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.

The role of DNA image cytometry in screening oral potentially malignant lesions using brushings: A systematic review

20-08-2019 – Madhurima Datta, Denise Laronde, Branko Palcic, Martial Guillaud

Journal Article, Review

It is believed that the majority of oral cancers develop from oral potentially malignant lesions (OPML). Though they can be easily detected during screening, risk stratification is difficult. During screening clinicians often find it difficult to distinguish OPMLs from benign lesions, and predicting OPML at risk of malignant transformation is particularly challenging. DNA aneuploidy has been known to be a marker of malignancy in a number of sites including the oral cavity.

We performed a systematic review to evaluate the effectiveness of DNA-ICM using brushings in differentiating OPMLs from benign/inflammatory lesions during screening and in predicting malignant transformation. MEDLINE, Pubmed, EMBASE electronic databases were systematically searched using a combination of keywords and subject headings. A total of 11 articles satisfied our inclusion criteria. These studies reported a wide range of sensitivity (16–96.4%) and specificity (90–100%) due to the differences in study design, definitions of high risk or low risk lesions and DNA-ICM protocol used. No long-term longitudinal studies were identified to assess the role of DNA-ICM using brushings in predicting malignant transformation. No studies evaluated the role of DNA-ICM in community screening settings. A number of studies combined DNA-ICM with other techniques like cytology or argyrophilic nucleolar organizer region counts leading to improved test results. In spite of DNA aneuploidy being accepted as a marker of malignancy, there is limited evidence of DNA-ICM using brushings being successful as an adjunct oral cancer screening tool. Longitudinal studies and large community screening studies need to be undertaken to draw stronger conclusion.

An ulceration on the tongue: A case report

23-08-2019 – Emmanuelle Vigarios, Aurore Siegfried, Benjamin Hebraud, Vincent Sibaud, Delphine Maret

Letter

Immune-checkpoint inhibitors in head and neck squamous cell carcinoma: cost-efficacy in second-line treatment based on programmed death-ligand 1 (PD-L1) level

23-08-2019 – Jacopo Giuliani, Andrea Bonetti

Letter

Potential role of autofluorescence imaging in determining biopsy of oral potentially malignant disorders: A large prospective diagnostic study

17-08-2019 – Linjun Shi, Chenxi Li, Xuemin Shen, Zengtong Zhou, Wei Liu, Guoyao Tang

Journal Article

Autofluorescence examination of oral tissues using the VELscope has been suggested as an adjunctive tool for cancer detection and diagnosis. This study aimed to determine the diagnostic value of VELscope in a large prospective study of 517 patients with oral potentially malignant disorders (OPMD). For the outcome assessments of discrimination of carcinoma form general OPMD and distinguishing high-risk lesions (moderate/severe dysplasia and carcinoma) from low-risk lesions (no/mild dysplasia), high sensitivity (100% and 95.9% respectively) and negative predictive value (100% and 98.2% respectively) were observed. All the carcinoma and showed loss of autofluorescence (LAF) and only 3 (0.6%) moderate/severe dysplasia were observed without LAF.

These data indicate that the cases without LAF using VELscope substantially rule out the presence of high-risk lesions including cancer. This may prove to be useful specially to alleviate patient anxiety regarding a clinically suspicious oral lesion without the LAF, and to avoid a unnecessary biopsy for these cases. Collectively, a perspective to highlight was that a no biopsy strategy may be appropriate for OPMD without LAF using VELscope after conventional oral examination.

Successful tri-modality treatment of atypical carcinoma ex-pleomorphic adenoma with more than 50 nodal metastases

14-08-2019 – Federico L. Ampil, Nestor de la Cruz

Letter

Carcinoma ex-pleomorphic adenoma (CEPA), an extremely aggressive malignant tumor, bears a significant potential for locoregional recurrence and distant metastases. Management of the disease usually involves definitive surgery with postoperative radiotherapy administered for identified nodal metastases. Two cases of CEPA with many (>50) cervical lymph node metastases and other histopathological features were managed by tri-modality treatment scheme. No evidence of disease occurred during follow-up of at least 2 years. These cases may eventually establish the value of surgery with adjuvant radiochemotherapy in patients with CEPA and supernumerary nodal metastases.

Clinical validation of the Salivary HPV DNA assessment and its link to the locoregional disease burden in advanced HPV associated oropharyngeal cancer

04-08-2019 – Rama Jayaraj, Chellan Kumarasamy, Madurantakam Royam Madhav, Sameep Shetty

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.

Limiting radiotherapy field to ipsilateral side only in unresected lateralised HPV positive N2b squamous cell carcinoma of the tonsil

17-06-2019 – Muhammad Shahid Iqbal, Josef Kovarik, Charles Kelly

Letter

Conceptual interpretation of findings on systematic review and meta-analysis of altered-fractionation radiotherapy improves local control in the early-stage glottic carcinoma

12-06-2019 – Rama Jayaraj, Chellan Kumarasamy, Shanthi Sabarimurugan, Madurantakam Royam Madhav, Sameep S. Shetty, Siddhartha Baxi

Letter

Together consideration of microenvironment and tumor cells: Analysis of papers published in Oral Oncology

11-06-2019 – Gargi S. Sarode, Sachin C. Sarode, Nilookumari Choudhary, Nilesh Kumar Sharma, Gopalakrishnan Dharmarajan, Shankargouda Patil

Letter

Corrigendum to ‘Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis’. Oral Oncol. 85 (2018) 60–67

09-06-2019 – Jie Jane Chen, Jeremy P. Harris, Christina S. Kong, John B. Sunwoo, Vasu Divi, Kathleen C. Horst, Sumaira Z. Aasi, S. Tyler Hollmig, Wendy Y. Hara

Published Erratum

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

09-06-2019 – Ana Karina Sarmiento L.

Letter