Oral Oncology

Molecular biology of oral cavity squamous cell carcinoma

10-01-2020 – Phillip J. Hsu, Kenneth Yan, Hailing Shi, Evgeny Izumchenko, Nishant Agrawal

Journal Article

Oral cavity squamous cell carcinoma (OCSCC) is a heterogeneous and complex disease that arises due to dysfunction of multiple molecular signaling pathways. Recent advances in high-throughput genetic sequencing technologies coupled with innovative analytical techniques have begun to characterize the molecular determinants driving OCSCC. An understanding of the key molecular signaling networks underlying the initiation and progression of is essential for informing treatment of the disease. In this chapter, we discuss recent findings of key genes altered in OCSCC and potential treatments targeting these genes.

Selective neck dissection in the treatment of head and neck squamous cell carcinoma patients with a clinically positive neck

17-01-2020 – Fernando López, Laura Fernández-Vañes, Patricia García-Cabo, Gianluigi Grilli, César Álvarez-Marcos, José Luis Llorente, Juan Pablo Rodrigo

Journal Article

Objective

To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (c
N+) at diagnosis.

Material and Methods

We retrospectively reviewed 159 patients with SCCHN with c
N+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death.

Results

A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the p
N classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered.

Conclusions

SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in c
N1 and c
N2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy.

Comorbidity in head and neck cancer: Is it associated with therapeutic delay, post-treatment mortality and survival in a population-based study?

10-01-2020 – Sabine Stordeur, Viki Schillemans, Isabelle Savoye, Katrijn Vanschoenbeek, Roos Leroy, Gilles Macq, Leen Verleye, Cindy De Gendt, Sandra Nuyts, Jan Vermorken, Claire Beguin, Vincent Grégoire, Liesbet Van Eycken

Journal Article

Objectives

This study aims to investigate the relationship between comorbidities and therapeutic delay, post-treatment mortality, overall and relative survival in patients diagnosed with squamous cell carcinoma of the head and neck (HNSCC).

Patients and Methods

9245 patients with a single HNSCC diagnosed between 2009 and 2014 were identified in the Belgian Cancer Registry. The Charlson Comorbidity Index (CCI) was calculated for 8812 patients (95.3%), distinguishing patients having none (0), mild (1–2), moderate (3–4) or severe comorbidity (>4). The relationship between CCI and therapeutic delay was evaluated using the Spearman correlation. Post-treatment mortality was modelled with logistic regression, using death within 30 days as the event. The association between comorbidity and survival was assessed using Cox proportional hazard models.

Results

Among 8812 patients with a known CCI, 39.2% had at least one comorbidity. Therapeutic delay increased from 31 to 36 days when the CCI worsened from 0 to 4 (rho = 0.087). After case-mix adjustment, higher baseline comorbidity was associated with increased post-surgery mortality (mild, OR 3.52 95% CI 1.91–6.49; severe, OR 18.71 95% CI 6.85–51.12) and post-radiotherapy mortality (mild, OR 2.23 95% CI 1.56–3.19; severe, OR 9.33 95% CI 4.83–18.01) and with reduced overall survival (mild, HR 1.39, 95% CI 1.31–1.48; severe, HR 2.41 95% CI 2.00–2.90). That was also the case for relative survival in unadjusted analyses (mild, EHR 1.77 95% CI 1.64–1.92; severe, EHR = 4.15 95% CI 3.43–5.02).

Conclusion

Comorbidity is significantly related to therapeutic delay, post-treatment mortality, 5-year overall and relative survival in HNSCC patients. Therapeutic decision support tools should optimally integrate comorbidity.

Prognostic and clinicopathological significance of PD-L1 and tumor infiltrating lymphocytes in hypopharyngeal squamous cell carcinoma

11-01-2020 – Chunyan Hu, Shu Tian, Lan Lin, Jiahao Zhang, Hao Ding

Journal Article

Objectives

Limited information is available regarding programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in hypopharyngeal squamous cell carcinoma (HPSCC). Therefore, we investigated the expression of PD-L1 and the volume of TILs in HPSCC to determine whether these biomarkers were associated with patient clinicopathologic characteristics and prognosis. Furthermore, we explored p16 status and analyzed its possible correlations with clinical outcomes.

Methods

Tissues of 111 HPSCC patients were immunohistochemically analyzed for PD-L1, CD8, CD4, and Foxp3 expression to assess the microenvironment. We also assessed the p16 status. The expression of PD-L1 and TILs were analyzed with respect to patient clinicopathologic variables and prognosis.

Results

Twenty-four (21.6%) patients had PD-L1 expression in ≥1% of tumor cells. PD-L1 expression was significantly correlated with a high level of TILs.

(P < 0.05). Kaplan–Meier analysis showed that higher CD8+ and Fox
P3+ TIL infiltration was strongly associated with superior overall survival (OS, P = 0.005 and P = 0.008) and disease-free survival (DFS, P = 0.015 and P = 0.048). Univariate and multivariate analyses confirmed that CD8+ TIL exhibited strong prognostic significance. The combination of PD-L1+ with CD8high expression was a prognostic factor and was associated with better OS (P = 0.025). Moreover, p16 positivity was detected in five patients (4.5%) and was only occasionally involved in HPSCC.

Conclusion

Our findings indicate that high CD8 and Fox
P3 expression in HPSCC contributes to longer patient survival. Although PD-L1 expression was not associated with outcome, PD-L1 positivity in combination with CD8high expression may have greater predictive potential.

MRI evaluation of involvement of parotid and submandibular glands by tongue squamous cell carcinoma

07-01-2020 – Aarati Panchbhai, Rahul Bhowate

Journal Article

Objectives

The majority of cases of salivary gland involvement are diagnosed in its late stages as may be missed in the evaluation, the low detection rate of involvement of salivary gland by OSCC may have significant impact on spread and recurrence of the OSCC.

The study aimed to evaluate involvement of parotid and submandibular salivary glands by tongue oral squamous cell carcinoma.

Material and method

The 144 histo-pathologically proven cases of tongue squamous cell carcinoma were evaluated for clinical staging, margins and extent of tumor and involvement of salivary gland on T1T2 Weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences and data was subjected to analysis.

Results

In tongue OSCC, total 9 (6.25%) patients showed salivary gland involvement, 2 of them involved parotid glands and 7 of them involved submandibular gland. The OSCC involving the salivary glands were in Stage 4 except for 2 cases with predilection for antero-lateral border and tendency towards midline crossing. Out of 9 cases that showed salivary gland involvement, the 5 cases showed direct involvement from the spreading lesion, the 3 cases showed the infiltration from adjacent lymph nodes and 2 cases showed infiltration from sublingual gland and medial pterygoid muscle.

Conclusion

The present study revealed the greater percentage of OSCC with salivary gland involvement as compared to previous studies; in contradiction present study demonstrated higher involvement of submandibular gland compared to parotid gland with additional imaging features in salivary glands (15.97%) suggesting the likely possibility of their involvement by OSCC in near future.

Oncological safety of submental island flap for reconstruction of pathologically node-negative and node-positive T1–2 oral squamous cell carcinoma-related defects: A retrospective study and comparison of outcomes

04-01-2020 – Jinbing Wang, Yiran Tan, Yi Shen, Mingming Lv, Jun Li, Jian Sun

Journal Article

Objectives

To evaluate the oncological safety and reliability of the submental island flap (SIF) technique in patients with pathologically node-negative (p
N0) and node-positive (p
N+) T1–2 oral squamous cell carcinoma (OSCC) undergoing surgical tumor resection and concurrent SIF reconstruction.

Patients and methods

Retrospectively, we reviewed patients with p
N0 and p
N+ T1–2 OSCC who underwent tumor resection and defect reconstruction with SIF from April 2008 to September 2016, focusing on flap viability, patterns and predictors of locoregional failure, salvage treatments, and oncologic prognosis.

Results

Of 160 patients with primary T1–2 OSCC, 33 were p
N+ and 127 were p
N0. All SIFs beside two were successful (98.75%). During follow-up, 18 patients experienced locoregional tumor relapse, of which 14 were p
N0 and four were p
N+. The 5-year recurrence-free survival was 88.73% vs. 86.93% for the p
N0 and p
N+ groups, respectively (p = .847). The p
N + patients had poorer prognosis than p
N0 patients (5-year overall survival, 66.35% vs. 91.10% respectively p = .005; disease-specific survival, 74.87% vs. 91.88% respectively p = .016). Multivariate analyses indicated there was no independent predictor for locoregional recurrence, but p
N+ was predictive for poor prognosis (p = .03).

Conclusion

SIF is a reliable flap for the reconstruction of OSCC-related small- and medium-sized soft tissue defect. With careful neck dissection and appropriate postoperative adjuvant treatment, the application of SIF did not increase the risk of locoregional tumor recurrence in patients with p
N+ T1–2 OSCC compared with those with p
N0 T1–2 OSCC.

The effectiveness of probiotics in prevention and treatment of cancer therapy-induced oral mucositis: A systematic review and meta-analysis

11-01-2020 – Zekai Shu, Peijing Li, Bingqi Yu, Shuang Huang, Yuanyuan Chen

Journal Article, Review

Oral mucositis (OM) is a common and troublesome adverse side effect of many cancer therapy modalities (chemotherapy, radiotherapy, and chemo-radiotherapy), which can cause pain, ulceration, dysphagia, malnutrition, even treatment interruption. Probiotics may be effective in preventing and treating of cancer therapy-induced OM. We performed a systematic review and meta-analysis of the effectiveness of probiotics in prevention and treatment of cancer therapy-induced OM. Four databases and one trial registry were searched as of the 12th of May 2019 to identify all eligible randomized controlled trials (RCT). Five studies involving 435 patients were included in this study. Methodological quality and outcomes were evaluated in every study included. Pooled results showed a moderate heterogeneity (P = 0.15, I2 = 44%). The pooled RRs indicated that the use of probiotics decreased the risk of OM for grade ≥3 (RR = 0.66, 95%CI = 0.54–0.81, P < 0.0001) as well as all grades (RR = 0.83, 95% CI = 0.72–0.97, P = 0.02). There was no significant difference between probiotics and placebo for cancer therapy completion rate (RR = 1.14, 95%CI = 0.65–2.00, P = 0.64). The subgroup analysis indicated that the use of probiotics was not statistically significant for patients receiving chemo-radiotherapy (RR = 0.52, 95% CI = 0.26–1.04, P = 0.07). In conclusion, probiotics may reduce the incidence and mitigate the severity of cancer therapy-induced OM. Further trials with a randomized, double-blind and multicentric study design are needed to confirm this effect. The PROSPERO registration number of this systematic review and meta-analysis is CRD42019130414.

The role of adjuvant (chemo-)radiotherapy in oral cancers in the contemporary era

10-01-2020 – Shao Hui Huang, Ezra Hahn, Simion I. Chiosea, Zhi-Yuan Xu, Ji-Shi Li, Lin Shen, Brian OSullivan

Journal Article

Squamous cell carcinoma of oral cavity (OSCC) is predominantly managed with surgery. Post-operative radiotherapy (PORT) and chemoradiotherapy (POCRT) enhance disease control in OSCC patients with adverse anatomic and pathologic primary and nodal features. Knowledge about disease behavior, surgery and radiotherapy advances, and the emergence of new systemic agents prompt refinement of PORT volumes and POCRT regimens. Traditional and emerging prognostic models that include adverse histopathological features underpin such approaches. This review summarizes research over recent decades with emphasis on the 2015 to Feb 2019 period describing: (1) Indications for PORT and/or POCRT, addressing surgical “margin status” including the definition of a “clear” margin to permit withholding PORT/POCRT; these concepts include characterizing the specimen yielding these measurements, the optimal time point to assess these findings, and the putative value of a “revised margin” performed during the same operative procedure, (2) Emerging prognostic factors including nodal burden (total number of involved lymph nodes) and perineural invasion, (3) PORT volume design, dose/fractionation and optimal surgery-to-PORT interval, (4) Chemotherapy dose, schedule, and agents, and (5) On-going clinical trials involving systemic agents and combinations of chemotherapy with immunotherapy.

Management of recurrent and metastatic oral cavity cancer: Raising the bar a step higher

15-12-2019 – Petr Szturz, Jan B. Vermorken

Journal Article

In recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN), the armamentarium of systemic anti-cancer modalities continues to grow in parallel with innovations in and better integration of local approaches. The backbone of cytotoxic chemotherapy remains cisplatin with 5-fluorouracil or a taxane. In contrast to cisplatin, the tumoricidal activity of carboplatin monotherapy is debatable. Adding the epidermal growth factor receptor (EGFR) inhibitor cetuximab to a platinum/5-fluorouracil doublet (the so-called EXTREME regimen) produced a statistically but also clinically significant improvement of survival and became thus the standard first-line palliative treatment in adequately fit patients. Interestingly, three large randomized trials (EXTREME, SPECTRUM, and ZALUTE) evaluating different anti-EGFR monoclonal antibodies (cetuximab, panitumumab, and zalutumumab, respectively) demonstrated preferential anti-tumour efficacy in patients with primary cancer in the oral cavity. Modern immunotherapy with immunomodulating antibodies, dubbed immune checkpoint inhibitors, such as anti-programmed cell death protein-1 (anti-PD-1) inhibitors nivolumab and pembrolizumab, showed unprecedented activity in one first-line (KEYNOTE-048) and several second-line trials (Check
Mate-141, KEYNOTE-012, KEYNOTE-055, and KEYNOTE-040). In a minority of also heavily-pretreated patients, these agents generate long-lasting responses without the typical chemotherapy-related toxicity, however, at a price of a low overall response rate, rare but potentially life-threatening immune-related adverse events, the risk of hyperprogression, and high costs. In oligometastatic disease, emerging data indicate long-term benefit with locally ablative techniques including metastasectomy and stereotactic radiotherapy of pulmonary but also hepatic and other distant lesions. In the frame of highly-individualized cancer care, a particularly intriguing approach is a combination of systemic and local therapies.

Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma

31-12-2019 – Lingeng Lu, Stephen G. Gaffney, Vincent L. Cannataro, Jeffrey Townsend

Journal Article

Objectives

To investigate how T-cell activation interacts with NSUN2 to influence HNSCC patient survival.

Materials and Methods

The relationships between T-cell activation status (Activation, Intermediate, and Exhaustion), NSUN2 expression, and patient survival were evaluated using Kaplan-Meier survival curves and multivariate Cox regression models in a public dataset with 520 HNSCC patients. HPV status was determined based on a Virus
Scan analysis of RNA-seq data.

Results

Among the patients with high NSUN2 expression, the Activation group exhibited longer survival than the Exhaustion group (trend P = 0.056). Adjusted hazards ratios (HRs) were 0.77 (95% CI: 0.49–1.19) for the Intermediate vs Exhaustion, and 0.61 (0.36–1.03) for Activation vs. Exhaustion. In contrast, there is a positive association between T-cell activation score and mortality in the patients with low NSUN2 expression (trend P = 0.016). The adjusted HRs were 1.97 (1.12–3.47) for the Intermediate vs Exhaustion, and 2.06 (1.16–3.68) for the Activation vs Exhaustion. In multivariate cox models with or without HPV status, the interaction between T-cell activation status and NSUN2 expression was statistically significant (P = 0.004 for with HPV status, and P = 0.002 for without, respectively). When not controlling for NSUN2 expression, there was no significant association between T-cell activation score and patient mortality (P = 0.84).

Conclusions

An interaction between NSUN2 expression and T-cell activation status affects patient survival in HNSCC regardless of HPV status, suggesting that NSUN2 is a potential precision marker for immune-checkpoint blockade, and a potential therapeutic target.

Low skeletal muscle mass is a strong predictive factor for surgical complications and a prognostic factor in oral cancer patients undergoing mandibular reconstruction with a free fibula flap

28-12-2019 – E. Ansari, N. Chargi, J.T.M. van Gemert, R.J.J. van Es, F.J. Dieleman, A.J.W.P. Rosenberg, E.M. Van Cann, R. de Bree

Journal Article

Background

Fibula free flaps (FFF) are effective in accomplishing successful reconstruction for segmental defects of the mandible. Potential risk factors for FFF complications have been described in previous research, e.g. age, comorbidity and smoking. Low skeletal muscle mass (SMM) has shown to be an emerging predictive factor for complications and prognostic factor for survival in head and neck cancer. This study aims to identify the predictive and prognostic value of low SMM for surgical FFF related complications, postoperative complications and survival in patients who underwent mandibular reconstruction with FFF after oral cavity cancer resection.

Materials and methods

A retrospective study was performed between 2002 and 2018. Pre-treatment SMM was measured at the level of the third cervical vertebra and converted to SMM at the level of the third lumbar vertebra (L3). SMM at the level of L3 was corrected for squared height. Low SMM was defined as a lumbar skeletal muscle index (LSMI) below 43.2 cm2/m2.

Results

78 patients were included, of which 48 (61.5%) had low SMM. Low SMM was associated with an increased risk of FFF related complications (HR 4.3; p = 0.02) and severe postoperative complications (Clavien-Dindo grade III-IV) (HR 4.0; p = 0.02). In addition low SMM was a prognosticator for overall survival (HR 2.4; p = 0.02) independent of age at time of operation, ACE-27 score and TNM stage.

Conclusion

Low SMM is a strong predictive factor for FFF reconstruction complications and other postoperative complications in patients undergoing FFF reconstruction of the mandible. Low SMM is also prognostic for decreased overall survival.

Patient-reported financial toxicity and adverse medical consequences in head and neck cancer

27-12-2019 – Whitney H. Beeler, Emily L. Bellile, Keith A. Casper, Elizabeth Jaworski, Nicholas J. Burger, Kelly M. Malloy, Matthew E. Spector, Andrew G. Shuman, Andrew Rosko, Chaz L. Stucken, Steven B. Chinn, Aleksandar F. Dragovic, Christina H. Chapman, Dawn Owen, Shruti Jolly, Carol R. Bradford, Mark E.P. Prince, Francis P. Worden, Reshma Jagsi, Michelle L. Mierzwa

Journal Article

Objectives

Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT.

Materials and methods

We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT.

Results

The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23–3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03–1.48), p = .02), and require supportive infusions (1.10 (1.02–1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14–2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment.

Conclusion

HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

Distinct biomarker and behavioral profiles of human papillomavirus-related oropharynx cancer patients by age

28-12-2019 – Carole Fakhry, Tim Waterboer, William H. Westra, Lisa M. Rooper, Melina Windon, Tanya Troy, Wayne Koch, Christine G. Gourin, Noemi Bender, Siddhartha Yavvari, Ana P. Kiess, Brett A. Miles, William R. Ryan, Patrick K. Ha, David W. Eisele, Gypsyamber DSouza

Journal Article

Background

HPV-positive oropharynx squamous cell cancer (HPV-OPC) patients were initially described as younger, however incidence has increased among older age-groups. It is unknown why some patients present at a younger age and others at a later age.

Methods

Multi-institutional prospective study of HPV-OPC cases (n = 163) and matched controls (n = 345) with detailed behavioral survey, and serum tested for HPV antibodies by fluorescent bead-based technology. Age at diagnosis was used to stratify patients into younger (≤50 years), middle-age (51–65), and older (>65).

Results

By age, demographic characteristics were largely similar, but HPV biomarkers and sexual acts differed. Younger cases were more likely to be HPV16-positive than older cases (100% vs 77%, p = 0.009). Similarly, younger cases were more likely to be HPV16 E6 or E7 seropositive (100% vs 82%, p = 0.03). Younger cases had a higher number of oral sex partners per year, a marker of sexual intensity (sex-years, p = 0.003), but a similar number of lifetime oral sex partners (measure of cumulative sexual exposure), compared to older cases. While sex-years were higher for younger cases and controls, cases had significantly higher sex-years than matched controls in each age-group (p < 0.001). Younger patients were also more likely to perform oral sex at sexual debut, and were younger at sexual debut (each p < 0.03).

Conclusions

Younger, middle-age and older HPV-OPC have distinct biomarker and behavioral profiles. Younger HPV-OPC cases have higher intensity of sexual exposure than older cases and controls, which may in part explain earlier disease onset. The distribution of HPV16-positive tumors among HPV-OPC differs by age group.

The value of preoperative radiotherapy in the treatment of locally advanced nasal cavity and paranasal sinus squamous cell carcinoma: A single institutional experience

24-12-2019 – Zekun Wang, Yuan Qu, Kai Wang, Runye Wu, Ye Zhang, Xiaodong Huang, Shiping Zhang, Jianping Xiao, Junlin Yi, Li Gao, Guozhen Xu, Jingwei Luo

Journal Article

Objectives

This study aimed to explore the value of preoperative radiotherapy in the comprehensive treatment of locally advanced nasal cavity and paranasal sinus squamous cell carcinomas (LA-NPSCCs).

Materials

This retrospective study included 140 patients with stage III-IVB NPSCCs treated with pre-/postoperative radiotherapy plus surgery. The complete resection rate, pathologic complete response (p
CR) rate, and orbital content retention rate were calculated. The overall survival (OS), local control (LC), distance metastasis free survival (DMFS) and disease-free survival (DFS) between treatment groups were evaluated.

Results

With a median follow-up of 92.3 months, the 5-year OS, LC, DMFS, and DFS of entire cohort were 62.0%, 65.5%, 85.4%, and 57.8%, respectively. The preoperative radiotherapy group achieved similar LC, DFS, DMFS, and OS rates compared to postoperative radiotherapy group, despite higher rates of stage IV and orbital content/apex invasion. The preoperative radiotherapy resulted in significantly improved complete resection rate (93.3% vs 38.0%, p < 0.001). In the preoperative radiotherapy group, one third of patients achieved pathologic complete response. The p
CR subgroup achieved statistically higher 5-year OS, LC, DFS (p < 0.05), but similar 5-year DMFS (p > 0.05) compared to non-p
CR subgroup. The actual orbital content retention rate in preoperative radiotherapy group was 85.7%, superior to 58.3% in postoperative radiotherapy group (p = 0.049).

Conclusion

On the basis of multimodality therapy becoming standard paradigm for LA-NPSCCs, preoperative radiotherapy significantly improved complete resection rate and orbital content retention rate. Therefore, preoperative radiotherapy followed by surgery might be desirable for LA-NPSCCs, especially for those with organ preservation intention.

Spleen tyrosine kinase expression is correlated with human papillomavirus in head and neck cancer

23-12-2019 – Morgan Black, Farhad Ghasemi, Ren X. Sun, William Stecho, Alessandro Datti, Jalna Meens, Nicole Pinto, Kara M. Ruicci, M. Imran Khan, Myung Woul Han, Mushfiq Shaikh, John Yoo, Kevin Fung, Danielle MacNeil, David A. Palma, Eric Winquist, Christopher J. Howlett, Joe S. Mymryk, Laurie Ailles, Paul C. Boutros

Journal Article

Objectives

Spleen tyrosine kinase (SYK) is a promoter of cell survival in a variety of cell types, including normal and cancerous epithelial cells. We hypothesized that SYK would an important therapeutic target to inhibit for the treatment of HNSCC.

Materials and methods

SYK protein abundance in patient tumours was evaluated. SYK protein and m
RNA abundance was used to examine patient survival and human papillomavirus (HPV) status. Small-interfering RNAs and gene editing with CRISPR/Cas9 were used to evaluate SYK expression on proliferation in HNSCC cell lines. The potency of SYK inhibitor ER27319 maleate on cellular proliferation was tested using a panel of 28 HNSCC cell lines and in vivo in HNSCC patient-derived xenograft (PDX) models.

Results

Moderate to high protein expression of SYK was observed in 24% of patient tumors and high SYK expression was exclusively observed in HPV-positive samples (p < 0.001). SYK inhibition with RNA interference, gene editing or a SYK inhibitor (ER27319) decreased cell proliferation and migration. Treatment of PDXs with ER27319 maleate was observed to reduce tumour burden in vivo in two of three models.

Conclusions

HPV-positive HNSCC harbours high SYK protein levels. We demonstrate that proliferation, migration and overall burden of these tumours can be reduced by genetic or pharmacologic inhibition of SYK. Taken together, these data establish SYK as a therapeutic target for HNSCC.

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab

22-12-2019 – Mioko Matsuo, Ryuji Yasumatsu, Muneyuki Masuda, Satoshi Toh, Takahiro Wakasaki, Kazuki Hashimoto, Masahiko Taura, Ryutaro Uchi, Takashi Nakagawa

Journal Article

Objectives

Immune-related adverse events (ir
AEs) have been shown to be associated with higher antitumor responses and a clinical benefit in non-small cell lung carcinoma, renal cell carcinoma, and melanoma patients. However, little is known regarding the association between ir
AEs and the clinical effect of nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC).

Materials and methods

We evaluated 108 patients treated with nivolumab for R/MHNSCC at 2 participating institutions. Ir
AEs were identified and profiled. We analyzed the association of each immune-related adverse effect with the clinical outcome of the patients.

Results

Among 108 patients, the objective response rate (ORR) was 29.6% (32/108 patients), and the disease control rate (DCR) was 50.0% (54/108 patients). Ir
AEs were observed in 41 patients (38.0%). Patients with ir
AEs had a significantly higher ORR and DCR than those without ir
AEs (46.3% vs. 19.4%, P = 0.004 and 75.6% vs. 34.3%, P < 0.001, respectively). The median progression-free and overall survival rates in patients with ir
AEs were significantly longer than in those without ir
AEs.

Conclusions

There was a significant relationship between ir
AEs and efficacy in R/MHNSCC patients treated with nivolumab. Our results indicate that the development of ir
AEs may aid in the earlier prediction of anticancer effects in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.

Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma

23-12-2019 – Roberto Carmagnani Pestana, Melody Becnel, Maria Laura Rubin, Danice K Torman, James Crespo, Jack Phan, Ehab Hanna, Diana Bell, Bonnie S Glisson, Jason M. Johnson, J. Jack Lee, Renata Ferrarotto

Journal Article

Objectives

Prior reports have demonstrated a potential enhancement in overall response rate (ORR) to chemotherapy after exposure to immunotherapy. The goal of this study was to evaluate the ORR and survival to chemotherapy and/or targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients who progressed on immune checkpoint inhibitors (ICI).

Materials and Methods

We retrospectively collected clinical and pathologic data from patients with recurrent/metastatic HNSCC who progressed on ICI and subsequently received chemotherapy or targeted therapy. ORR was assessed by RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results

A total of 43 patients met criteria for inclusion. The majority were male (91%) and former smokers (60%). Most patients received ICI as first-line (58.14%); the vast majority was platinum exposed (90.7%). The ORR to ICI was 21%. The ORR to systemic therapy before ICI was 47%, and the ORR after ICI failure was 42%. After progression on ICI, the median PFS and OS on the subsequent line of therapy were 4.2 and 8.4 months respectively.

Conclusion

In our cohort of recurrent/metastatic HNSCC patients, the ORR and OS to systemic therapy after progression on ICI were higher than historical controls for second-line or beyond. Further investigations are warranted to better characterize optimal sequencing and combination strategies.

Head and neck free flap survival when requiring interposition vein grafting: A multi-instiutional review

22-12-2019 – Nolan B. Seim, Matthew Old, Daniel Petrisor, William Thomas, Akash Naik, Alia J. Mowery, Stephen Kang, Ryan Li, Mark K. Wax

Journal Article

Objective

Interposition vein grafting in free flap reconstruction is often viewed as a risky procedure, but is necessary in cases of inadequate pedicle length.

Materials and methods

Two tertiary care centers retrospectively.reviewed 3008 head and neck free flap reconstructions from 2008 to 2017 91 patients were identified requiring interposition vein grafting during reconstruction. Pre and perioperative characteristics were recorded Univariate and multivariate analyses were conducted with a p value <0.05 indicating statistical significance.

Results

Of the 91 patients 75% had undergone reconstruction for cancer, 66% of these cases were in the setting of recurrence or complication, 33% had a previous free flap, and 52% had prior radiation therapy. Surgical site was primarily craniofacial (36%) or oral cavity (26%). The majority of vein grafts were saphenous (64%), average graft length 18 cm (SD 11 cm). Half were used for both artery and vein anastomosis. Flap survival was 85% overall and only prior free flap was predictive of failure on multivariate analysis. No other peri-operative or graft variable assessed in this study were predictive of flap failure.

Conclusion

In a multi-institutional study of head and neck free flap reconstructions using interposition vein grafts, we identified an overall 85% success rate with no significant difference between soft tissue and osteocutaneous flaps despite the complicated nature of these cases.

Virtual Surgical Planning in Subscapular System Free Flap Reconstruction of Midface Defects

23-12-2019 – Brian P. Swendseid, Dylan F. Roden, Swar Vimawala, Tony Richa, Larissa Sweeny, Richard A. Goldman, Adam Luginbuhl, Ryan N. Heffelfinger, Shachika Khanna, Joseph M. Curry

Journal Article

Objectives

Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position.

Materials and Methods

Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution.

Results

Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31–3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0–1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2–55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative ‘ideal’ bone position was <1 cm in 82% of measurements. There were no flap losses.

Conclusion

VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost.

The feasibility and survival mechanism of a large free flap supported by a novel hybrid perfusion mode

22-12-2019 – Xiaobin Luo, Junling Liu, Hongyu Chen, Baolong Li, Zeyuan Jin, Mengyao Zhao, Yutong Xie, Chenxin Yu, Xijie Zhou, Bin Zhao, Hede Yan

Journal Article

Objectives

In this study, we presented a novel hybrid perfusion mode in an attempt to provide a new strategy to improve the survival of an extended large flap and discuss its possible mechanisms.

Materials and Methods

A 14 × 10 cm flap was designed on the rabbit abdomen. Ninety-six rabbits were randomly divided into three groups based on the flap perfusion mode: control group I (CON 1, physiological perfusion mode with bilateral deep inferior epigastric vascular pedicles intact), control group II (CON 2, physiological perfusion mode with single deep inferior epigastric vascular pedicle intact), hybrid nourished group (physiological perfusion as in CON 2 combined with arterialized venous nonphysiological perfusion mode, referred to as a hybrid perfusion mode). Flap survival, status of vascular perfusion, microvasculature, histopathology, expression of CD34, e
NOs, VEGF and metabolic status of the flaps by LC-MS were assessed in each group.

Results

The results of “hybrid nourished” flaps were similar to the traditional flaps in terms of flap survival, level of vascular perfusion and microvasculature except the status of metabolites.

Conclusions

The feasibility of this novel hybrid perfusion mode will greatly extend the indications of flap transfer and efficiently improve the survival reliability of large flaps. In a sense, this mode will be an ideological emancipation for the field of flap surgery.

Skeletal muscle mass is an imaging biomarker for decreased survival in patients with oropharyngeal squamous cell carcinoma

20-12-2019 – N. Chargi, S.I. Bril, J.E. Swartz, I. Wegner, S.M. Willems, R. de Bree

Journal Article

Objectives

Low skeletal muscle mass (SMM) and sarcopenic obesity (co-presence of low SMM and obesity) are emerging prognosticators in oncology, but the prevalence and prognostic value in oropharyngeal squamous cell carcinoma (OPSCC) is not yet known.

Materials and methods

Patients with OPSCC, curative treatment intention and pre-treatment diagnostic imaging of the head and neck area were included. Patients with unknown HPV-status, palliative treatment intention or unavailable imaging were excluded, Relevant demographic and clinical characteristics were collected between 2009 and 2016. Patients were stratified into a low-, intermediate-, and high-risk group according to HPV-status, amount of pack-years, tumor and nodal stage. SMM was radiologically measured and cutoff values were determined by optimal stratification. The prognostic value of low SMM and sarcopenic obesity for overall survival (OS) and disease-free survival (DFS) was determined by Cox regression analysis and Kaplan Meier survival curves.

Results

In 216 patients, low SMM and sarcopenic obesity were present in 140 (64.8%) and 13 (6.0%) patients, respectively. On multivariate analysis, stratification into a high-risk group (HPV-negative status with ≥10-pack-years or T4-stage) was a prognostic factor for OS and DFS (HR 2.93, p < 0.01) (HR 4.66, p < 0.01). Of specific interest, sarcopenic obesity was a strong negative prognostic factor for OS and DFS (HR 4.42, p < 0.01 and (HR 3.90, p < 0.05), independent from other well-known prognostic factors such as HPV-status.

Conclusion

Low skeletal muscle mass is highly prevalent in OPSCC patients. Sarcopenic obesity is a novel pretreatment prognosticator for OS and DFS in OPSCC and should therefore be considered in clinical decision making.

The efficacy of chemotherapy in survival of stage II nasopharyngeal carcinoma

17-12-2019 – Xin-Bin Pan, Ling Li, Song Qu, Long Chen, Shi-Xiong Liang, Xiao-Dong Zhu

Journal Article

Purpose

Chemotherapy use remains controversial for stage II nasopharyngeal carcinoma (NPC). This retrospective study was conducted to identify whether chemoradiotherapy was associated with better survival compared to radiotherapy.

Materials and methods

The Surveillance, Epidemiology, and End Results (SEER) database was queried for stage II NPC patients between 2004 and 2015. Patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer-specific survival (CSS) were examined using the Kaplan-Meier method, Cox proportional hazards models, and propensity score matching analyses.

Results

This study examined 908 patients, including 102 receiving radiotherapy and 806 receiving chemoradiotherapy. Chemoradiotherapy was associated with 5-year OS (78.01% vs. 75.12%; p = 0.22) and CSS (78.92% vs. 78.26%; p = 0.40) rates comparable to those of radiotherapy. Propensity score matching analyses demonstrated similar OS (HR: 0.63, 95% CI: 0.36–-1.10; p = 0.10) and CSS (HR: 0.77, 95% CI: 0.41–1.48; p = 0.44) rates with radiotherapy. Age >60 years and non-Asian patients were associated with worse survival.

Conclusion

This study revealed that chemoradiotherapy showed similar survivals to stage II NPC patients compared with radiotherapy. Due to the limitations of SEER database, further studies should be performed to verify the results.

Validation and characterisation of prognostically significant PD-L1+ immune cells in HPV+ oropharyngeal squamous cell carcinoma

16-12-2019 – Richard J. Young, Mathias Bressel, Sandro Porceddu, Janez Cernelc, Peter Savas, Howard Liu, Damien Urban, Alesha A. Thai, Caroline Cooper, Tsien Fua, Paul Neeson, Danny Rischin, Benjamin Solomon

Journal Article

We previously showed in human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) that the presence of intratumoral (IT) PD-L1+ immune cells (ICs) or CD8+ infiltrating ICs are of prognostic value. Here we report the prognostic significance of these immune biomarkers in an independent validation cohort of 177 HPV+OPSCC patients. IT and stromal (S) localisation of PD-L1+ and CD8+ ICs were scored. High abundance (≥5%) of PD-L1+ IT ICs was found in 51/167 patients (30.5%) and was associated with improved overall survival (OS) (HR, 0.21; 95% CI, 0.05–0.91; P = 0. 012) validating our previous results. High abundance (≥30%) of CD8+ IT or S ICs, found in 77/167 patients (46.1%) provided a HR of 0.45 for OS however the confidence interval was wide (95% CI 0.16–1.25, p = 0.105). Multiplex immunohistochemistry revealed CD68+ macrophages and CD3+CD8+ T cells to be the most common ICs expressing PD-L1. Gene expression analysis showed tumors with high abundance of PD-L1+ IT ICs exhibit gene signatures associated with responses to PD1 or PD-L1 inhibitors pembrolizumab and atezolizumab. These data support the role of immune biomarkers such as PD-L1+ ICs to identify subgroups of HPV+OPSCC patients with an excellent outcome that may be suitable for trials evaluating de-intensification of therapy.

Neck management in patients with olfactory neuroblastoma

14-12-2019 – Xinmao Song, Chuang Huang, Shengzi Wang, Li Yan, Jie Wang, Yi Li

Journal Article

Objective

Optimal neck management in patients with olfactory neuroblastoma (ONB), a rare malignancy, remains uncertain. This study aimed to analyse patterns of cervical lymph node metastases and corresponding clinical outcomes and to investigate the value of elective neck irradiation (ENI) in this population.

Methods and materials

This study retrospectively reviewed clinical records, imaging findings, nodal metastasis features and treatment data of 217 patients with ONB treated at our hospital during 1991–2019. Univariate and multivariate analyses were used to assess the influence of cervical lymph node involvement on treatment outcomes. Survival and regional failure rates were compared between patients with or without ENI.

Results

Thirty-two patients (14.7%) presented initially with cervical lymph node metastases, most frequently at levels II (10.6%, 23/217) and VIIa (5.5%, 12/217). Patients with and without cervical node metastasis differed significantly in overall (OS) (41.9% vs. 86.1%, p < 0.001), progression-free (PFS) (41.9% vs. 84.8%, p < 0.001), regional failure-free (45.9% vs. 89%, p < 0.001) and distant metastasis-free survival (41.5% vs. 86.1%, p < 0.001). Cervical lymph involvement was an independent factor affecting poor OS (hazard ratio, 0.184, 95% confidence interval, 0.078–0.436, p < 0.001) and PFS (hazard ratio, 0.198, 95% confidence interval, 0.088–0.445, p < 0.001). Moreover, 43.8% patients (95/217) underwent ENI, which significantly reduced the incidence of regional recurrence from 10.7% to 3.2% (χ2 = 4.396, p = 0.036) but did not significantly affect other survival outcomes. Regional failures could be resolved using salvage treatment.

Conclusions

Our findings indicate the importance of systematic therapy for patients with initial cervical lymph node metastases. ENI is not recommended for N0 disease.

Assessing the validity of EQ-5D-5L in people with head & neck cancer: Does a generic quality of life measure perform as well as a disease-specific measure in a patient population?

14-12-2019 – A. Davies, A. Waylen, S. Leary, S. Thomas, M. Pring, B. Janssen, R. Beynon, S. Lang, S. Schimansky, K. Hurley, A. Ness

Journal Article

Background

Head and neck cancer (HNC) is an important cause of morbidity and mortality globally. Radical treatment methods may result in facial disfigurement and/or functional difficulties with subsequent adverse impacts on health-related quality of life (HRQoL). Guidelines suggest that HRQoL should be measured repeatedly throughout treatment to enable refined treatment protocols and tailored follow-up support but questionnaires are often long and burdensome. We compared condition-specific and generic metrics to assess HRQoL for people with this condition.

Methods

We used data from the prospective Head and Neck 5000 clinical cohort study – 5511 participants with a new diagnosis of HNC between 2011 and 2014. HRQoL data were collected at baseline from 2065 people who completed both the condition-specific EORTC-QLQ-C30 and the shorter, generic EQ-5D-5L questionnaires.

Results

There was strong evidence of association between comparable scales on each questionnaire at baseline: higher levels of functioning and lower levels of reported symptoms assessed with EQ-5D-5L were associated with lower EORTC-QLQ-C30 symptom scores. A moderate relationship (0.61) was found between overall QoL in the EQ-5D-5L index and self-perceived health (EQ VAS).

Conclusions

HRQoL data collected from the generic EQ-5D-5L and cancer-specific EORTC-QLQ-C30 questionnaires are comparable at baseline for people diagnosed with HNC. This would allow a reduced burden of data collection but the EQ-5D-5L may not be sensitive to some condition-specific symptoms. Clinicians and researchers must clarify their aims and outcomes of interest before choosing their HRQoL measures. Further work is required to examine the ability to detect change in these measures over time.

The future of robotic surgery in otolaryngology – head and neck surgery

17-12-2019 – Akina Tamaki, James W. Rocco, Enver Ozer

Journal Article, Review

Robotic surgery for management of head and neck pathologies has only been in practice for little more than a decade. Since then, there has been a rapid development in the field of transoral robotic surgery (TORS) and robotic surgery in otolaryngology. TORS has emerged as a tool in the treatment of both malignant and benign oropharyngeal, hypopharyngeal, and laryngeal disease. TORS is also a critical component of ongoing clinical trials seeking to improve the treatment of oropharyngeal squamous cell carcinoma. In addition, it’s application has expanded to treatment of obstructive sleep apnea, thyroid and parathyroid disease, and skull base pathologies. This review will provide an overview of the current application of robotics in otolaryngology as well as highlight the developing robotic platforms and technologies, and future of the field.

Treatment of end-stage pharyngeal strictures after laryngectomy with fasciocutaneous microvascular reconstruction

12-01-2020 – Janice L. Farlow, Andrew J. Rosko, Matthew E. Spector

Letter

Pharyngeal strictures can develop after laryngectomy for larynx cancer, particularly in combination with radiation. Some patients develop intractable strictures where conservative swallowing therapy and pharyngeal dilations fail. Secondary reconstruction of these patients has not been described in the literature. We report our experience with completion pharyngectomy and fasciocutaneous free tissue reconstruction for this patient population. Five subjects who had undergone laryngectomy and radiation were successfully reconstructed with fasciocutaneous free tissue transfer using the radial forearm or anterolateral thigh with minimal post-operative complications. Following surgery, enteral tube feeding requirements were eliminated, and all diets were advanced. A few patients still required a modified diet or continued dilations. We thus demonstrate that pharyngectomy with secondary reconstruction is an effective option for end-stage pharyngeal strictures, though this should only be undertaken with careful patient selection.

HPV testing: A quality metric

04-01-2020 – Antoine Eskander, Zain A. Husain

Editorial

Financial burden of oral squamous cell carcinoma in India

24-12-2019 – Rahul Anand, Deepak Pandiar, Mala Kamboj

Letter

Increased clinical and plasma EBV DNA responses to platinum-gemcitabine after nivolumab in patients with heavily platinum-pretreated nasopharyngeal cancer

24-12-2019 – S. Cabezas-Camarero, R. Pérez-Alfayate, F. Puebla, M.N. Cabrera-Martín, P. Pérez-Segura

Letter

Metachronous mediastinal and lung metastases from head and neck cancer: A case series, literature review and considerations for treatment

22-12-2019 – Federico Ampil, Carlos Previgliano, Carrie Porter, Troy Richards, Amol Takalkar

Letter

Metachronous mediastinal and lung metastases (MMLM), important sources of morbidity and mortality, in people with head and neck cancer (HNC) have received little attention. Between 1980 and 2004, 37 patients with treated HNC and MMLM diagnosed on follow-up imaging (with histological confirmation in 14 cases) were identified. The median interval from diagnosis of HNC to the appearance of MMLM was 14.5 months. The overall median survival was 4 months, and the 1-year crude survival rate (CSR) was 16%. A meaningful difference in the 1-year CSRs between the palliative radiation treated and untreated subjects (39% and 4%, respectively, p < 0.01) was observed. Because associated costs of health care utilization are considerable, and yet survival is limited, optimum management of MMLM-HNC with improvement of prognosis remains a challenge.

Intolerance to pungent spices among patients receiving radiation and chemotherapy for head and neck cancers

21-12-2019 – Akanksha Aanya, Prasanna Suresh Hegde, Christine Alexis Fernando, Shalini Thakur, Vishal Rao

Letter

Corrigendum to “Cutaneous keratinocyte cancers of the head and neck: Epidemiology, risk factors and clinical, dermoscopic and reflectance confocal microscopic features” Oral Oncol. 98 (2019) 109–117

16-12-2019 – Katie J. Lee, Mitchell Robinson, H. Peter Soyer

Published Erratum

Chemotherapy after progression on nivolumab is essential for responders with genetic alterations of driver gene: Review of two recurrent/metastatic oral squamous cell carcinoma patients

17-12-2019 – Kazuhiro Ogi, Junichi Kobayashi, Takafumi Nakagaki, Junya Okamoto, Kazushige Koike, Naoki Hirokawa, Masanori Someya, Hiroki Sakamoto, Kohichi Takada, Takashi Tokino, Yasushi Sasaki, Hiroyoshi Hiratsuka, Akihiro Miyazaki

Letter

Follicular dendritic cell sarcoma of the parotid gland: A case report

17-12-2019 – Pugen An, Yizhou Li, Jizhi Zhao

Letter

Follicular dendritic cell sarcoma (FDCS) is an exceedingly rare malignant neoplasm. The management of this tumor is fully challenging due to its rarity and lack of documentations. We share a case with primary parotid FDCS. This case report depicts the clinicopathological features of FDCS, which intends to serve as a reference to clinicians in its correct identification.

Radiation induced hypothyroidism – Why is early intervention necessary?

05-12-2019 – Kshitij Aggarwal, Shalini Thakur, Vishal Rao, Sameep S. Shetty

Letter

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

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

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

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.”

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

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