INTRODUCTION:Buccal mucosa cancers are the most prevalent oral cavity cancers in South Asia, often attributed to widespread tobacco use. The current NCCN guidelines generally advise against primary surgery for locally very advanced (cT4b) buccal cancers involving the masticatory space and infratemporal fossa (ITF). However, some surgeons have adopted an aggressive surgical approach for T4b oral squamous cell carcinoma, involving composite resections and ITF clearance. MATERIALS AND METHODS:This is a retrospective analytical survival study of 91 patients with very locally advanced buccal mucosa cancers with involvement of ITF (cT4b), who underwent radical surgery in the form of bi-alveolar composite resection with ITF clearance and Modified Neck Dissection from 2017 to 2023. RESULTS:At a median follow-up of 27 months, 54.9% of patients were alive and disease-free. The estimated mean 3-year overall survival (OS) and disease-free survival were 48% and 44%, respectively. In multivariate survival analysis, maxillary sinus involvement (p = 0.008), no response to neoadjuvant chemotherapy (p = 0.004), and nodal involvement (p = 0.05) were independent predictors of poor OS. Patients with high ITF involvement (n = 23) had a higher rate of distant metastasis compared to those with low ITF involvement (n = 68; p < 0.015). Presence of extra-nodal extension also significantly reduced survival across both groups (median OS: 10 months vs. 6.8 months; p = 0.037). CONCLUSION:ITF clearance is a safe and effective approach for managing locally very advanced (cT4b) buccal cancers.

AIM:High-grade neuroendocrine carcinoma of the head and neck (HN-NEC) is a rare, aggressive malignancy with limited evidence on outcomes with multimodality therapy. MATERIALS AND METHODS:This single-centre retrospective cohort study (2011-2020) analysed 48 newly diagnosed patients with poorly differentiated HN-NEC treated with curative intent. Multimodality therapy comprised neoadjuvant chemotherapy (NACT) in patients with advanced disease, followed by surgery with adjuvant (chemo)radiotherapy or definitive chemo-radiotherapy. Primary outcomes were overall survival (OS) and progression-free survival (PFS); major pathological response (MPR) was defined as ≤10% residual tumour post-NACT. RESULTS:Median age was 45 years (IQR = 32-58); 85% had sinonasal primaries. Thirty-nine patients (81.2%) received NACT, while eight underwent primary surgery. At a median follow-up of 88.3 months, 5-year OS and PFS were 48% (95% CI: 35.2-65.3) and 36.7% (24.8-54.3), respectively. Age<50 years (p = 0.024), advanced local stage (p = 0.02), nodal metastasis (p = 0.058), and non-sinonasal primary (p = 0.02) were independent predictors of poor OS. MPR predicted significantly better 5-year OS (85.7% vs 18.5%, p = 0.019). Most patients failed at distant sites (57.7%). Only two patients (4.2%) developed brain metastases; none received prophylactic cranial irradiation (PCI). Elective nodal irradiation (ENI) significantly improved regional control (100% vs 68.6% at 5 years; p = 0.037). CONCLUSION:Multimodality therapy integrating NACT, surgery, and radiotherapy optimises outcomes in advanced HN-NEC. Younger age, non-sinonasal origin and higher locoregional extent are poor prognostic factors, while MPR post-NACT achieves excellent survival. ENI should be considered in curative regimens. Omitting PCI appears to be safe. Future research should focus on therapeutic strategies for NACT non-responders and optimise systemic control.

BACKGROUND:Oral squamous cell carcinoma (OSCC) frequently progresses during delays before definitive treatment, yet the biological behavior of tumours during this interval remains poorly characterized. We prospectively evaluated tumour growth kinetics, stage progression, and anatomic pathways of spread using serial pre-treatment imaging. METHODS:This prospective observational study included 483 patients with treatment-naïve OSCC treated between July 2020 and December 2023. Eligible patients underwent at least two clinically indicated pre-treatment imaging studies separated by ≥ 3 weeks. Gross tumour volume (GTV), tumour volume doubling time (TVDT), stage progression, and subsite-specific spread patterns were analyzed and correlated with survival outcomes. RESULTS:The median interval between serial imaging studies was 7.1 weeks. Median tumour volume increased from 12.9 cm3 to 19.4 cm3, corresponding to a median growth rate of 7.3% per week and a median TVDT of 7.9 weeks. Stage progression occurred in 30% of patients, while nodal progression was observed in 23%. Tongue tumours demonstrated predominantly longitudinal spread, buccal tumours extended laterally and posteriorly, alveolar tumours showed early bone invasion, and retromolar trigone tumours preferentially invaded deep spaces. Patients with TVDT ≤ 8 weeks demonstrated significantly worse survival. CONCLUSIONS:OSCC demonstrates rapid progression during untreated intervals and follows reproducible subsite-specific pathways of spread.

Neuroendocrine tumors (NETs) are rare entity and most common location in head and neck region is larynx. Given the rare occurrence, only few studies exist describing prognosis and management of these cancers. The case presented below is a grade 2 well-differentiated NET which is unique in its location, grade discordance and intermediate prognosis. Additionally, we reviewed the existing literature for tumour characteristics, diagnosis, grouping, treatment modalities and prognosis.

ABSTRACT Objectives HPV‐negative oropharyngeal squamous cell cancer (OPSCC) is associated with poor clinical outcomes. The main objective of this study was to evaluate prognostic factors of OPSCC treated with definitive chemoradiotherapy (CTRT). Materials and Methods Consecutive patients of OPSCC treated with definitive CTRT in a tertiary care center from January 2013 to December 2017 were analysed retrospectively. Kaplan–Meier method was used for survival analysis, Log‐rank test was used for univariate analysis (UVA), and Cox regression method was used for multivariate analysis (MVA). Results Out of 630 eligible patients, 543 (86.1%) had locally advanced stage according to AJCC 7th edition. HPV status was known for 500 patients, of which 55 (11%) tested p16 positive, reflecting a predominantly HPV‐negative cohort. Chemo‐radiotherapy was offered to 447 (71%) patients. Intensity‐modulated‐radiotherapy (IMRT) technique was used for 163 (25.9%) patients. On UVA KPS ≤ 80 (p = 0.001), p16 negative tumours (p < 0.001), T3‐T4 stage (p < 0.001), advanced group stage (AJCC 8th ed.) (p < 0.001), conventional RT technique (p < 0.001), RT dose < 66 Gy EQD2 (p < 0.001) and residual disease after treatment (p < 0.001) were associated with poor Locoregional control (LRC) rates. On MVA p16 negative tumours (HR 3.1 [95% CI 1.8–5.3]), T3‐T4 stage (HR 1.6 [95% CI 1.2–2.2]), conventional RT technique (HR 1.6 [95% CI 1.5–2.3]), RT dose < 66 Gy EQD2 (HR 2.2 [95% CI 1.5–3.4]) were independent prognostic factors for poor LRC. These variables were also significant for local control, disease‐free free and overall survival. Conclusion In this predominantly HPV‐negative OPSCC cohort, HPV status, T stage, RT technique, and RT doses > 66 Gy were independent prognostic factors for all outcomes.

IDH-mutant (IDHmt) high-grade gliomas (HGG) differ significantly from IDH-wildtype (IDHwt) HGG, or glioblastoma (GBM). MGMT promoter methylation (MGMTp) is an established prognostic marker in GBM, but its role in IDHmt HGG remains unclear. We evaluated the prognostic impact of IDH mutation and MGMTp in 395 uniformly treated HGG patients in India. All patients underwent maximal safe resection followed by adjuvant radiotherapy and concurrent plus maintenance temozolomide (TMZ). MGMTp was assessed by methylation-specific PCR, and IDH1/2 mutations by immunohistochemistry and targeted sequencing. Median age was 50 years; median follow-up was 63 months. IDH mutations were present in 15.4 % of patients, and MGMTp in 36.7 %. Median overall survival (OS) was 19 months; 2-year OS was 41.5 %. Age > 50 years (HR 1.77, p < 0.001), <6 cycles of TMZ (HR 2.3, p < 0.001), and IDHwt status (HR 3.02, p < 0.001) predicted poorer outcomes. MGMTp status did not impact OS in IDHmt patients (p = 0.97). However, in IDHwt patients, unmethylated status was associated with worse OS (HR 3.66, p < 0.001) compared to methylated (HR 2.16, p = 0.009). These findings reaffirm the prognostic significance of IDH mutations and MGMTp methylation in GBM, underscoring their relevance in clinical stratification and treatment planning.

BACKGROUND:Acute toxicity is a key endpoint in head and neck radiotherapy (RT) and chemoradiotherapy (CRT) trials and is most commonly reported as maximum toxicity per patient. However, the reproducibility of clinician-reported toxicity grading remains incompletely characterized. We evaluated interobserver agreement in acute toxicity assessment, focusing on maximum toxicity as the primary endpoint. METHODS AND MATERIALS:This predefined subgroup analysis was conducted within a prospective randomized controlled trial of patients with head and neck squamous cell carcinoma (HNSCC) undergoing curative-intent RT/CRT. Acute toxicities were assessed weekly using CTCAE v5.0 by two independent, blinded radiation oncologists. Four domains were evaluated: dermatitis, oral mucositis, dysphagia, and xerostomia. The primary endpoint was patient-level maximum toxicity, dichotomized as ≥Grade 2 and ≥Grade 3. Interobserver agreement was assessed using Cohen's κ. RESULTS:Seventy-four patients were included. For maximum ≥Grade 2 toxicity, incidence (O1 vs O2) was: dermatitis 55.4% vs 45.9%, mucositis 91.9% vs 70.2%, dysphagia 95.9% vs 91.9%, and xerostomia 55.4% vs 58.1%, with κ of 0.33, 0.35, 0.41, and 0.23, respectively (fair to moderate). For ≥Grade 3 toxicity, κ values were: dermatitis 0.79, mucositis 0.41, dysphagia 0.63, and xerostomia 0.25. Pooled weekly agreement for ≥Grade 2 toxicity was higher (κ = 0.49-0.89), with peak concordance during weeks 5-6. CONCLUSIONS:Interobserver agreement for maximum acute toxicity was fair to moderate across domains in head and neck RT/CRT, with the largest discordance for oral mucositis even between observers at the same centre. Although maximum toxicity remains a pragmatic and widely used endpoint, caution is warranted in its interpretation, and weekly assessment may offer a more reproducible complementary endpoint, particularly for cross-trial comparisons.

INTRODUCTION:There is limited evidence on the role of adjuvant external beam radiotherapy in differentiated thyroid cancer (DTC). METHODS:We conducted a retrospective study of patients with DTC treated with adjuvant Intensity Modulated radiotherapy (IMRT) from 2011 to 2024. RESULTS:Fifty-nine patients were analyzed with median follow-up of 53 months. All the patients had undergone total thyroidectomy. Gross extrathyroidal extension was seen in 76% of patients, while 54% had R1/R2 resection. High-risk histological types were seen in 51% of patients, while 34% had recurrent disease. The 5-year locoregional control (LRC) was 89.3% while 5-year overall survival (OS) was 84.6%. Acute Grade 3 dermatitis and dysphagia were seen in 12% and 10%, respectively. Late toxicity, including tracheostomy placement and feeding tube dependence, was seen in three and one patient, respectively. CONCLUSION:Adjuvant IMRT in patients with DTC with high risk of locoregional recurrence resulted in good LRC with acceptable toxicities.

Oral cavity squamous cell carcinoma (OCSCC) is the second most common cancer in India with an age standardised ratio of 10.3 per 100,000 (both sexes combined) (1). Most patients (60%-80%) present in advanced stages with a high risk of nodal involvement. The current standard of care involves surgery followed by adjuvant radiotherapy (RT), often including elective nodal irradiation (ENI) even in pathologically node-negative patients. However, recent evidence suggests that well-selected patients with adequate surgical clearance may be adequately treated with limited volumes of ENI, potentially sparing them unnecessary toxicity. The APRON study is a single-arm, phase II trial evaluating whether limiting ENI is non-inferior to standard adjuvant RT in carefully selected patients with lateralized oral cavity cancers. Eligible patients are adults with biopsy-proven squamous cell carcinoma of the bucco-alveolar region or oral tongue who have undergone margin-negative resection and adequate elective nodal dissection (≥18 nodes). Only well-lateralized tumours (≥1 cm from midline for tongue cancers) are included. The primary endpoint is regional control at 2 years, defined as any nodal recurrence (ipsilateral or contralateral). Secondary endpoints include swallowing function (MD Anderson Dysphagia Inventory; modified barium swallow), local and regional recurrence-free survival, disease-free and overall survival, acute/chronic toxicity, quality of life, salvage rates for recurrence, and dosimetry comparisons. The study also assesses the safety and efficacy of moderate hypofractionation (50 Gy/20 fractions) in the adjuvant setting. A sample size of 106 patients is planned, with early stopping rules for safety. Statistical analysis will use the Clopper-Pearson method for nodal failure rates and propensity score matching with historical controls for non-inferiority testing. By limiting ENI in well-selected patients, APRON aims to reduce treatment-related morbidity while maintaining oncologic efficacy, potentially improving functional outcomes and preserving regional immune function. The study is expected to provide valuable evidence for de-escalated adjuvant strategies in OCSCC management. CTRI NUMBER: CTRI/2025/03/082341.

PURPOSE:To report the impact of didactic lectures with hands-on cadaveric training for head and neck brachytherapy (BT) as part of a teaching course. MATERIALS AND METHODS:The 1st BT teaching course under Elekta BrachyAcademy for head and neck cancer (HNC) and breast cancer was conducted at Tata Memorial Hospital, Mumbai, India. Didactic lectures with cadaveric workshop and hands-on training for planning procedure were taught to the participants. Both precourse survey and postcourse evaluation were conducted. RESULTS:Total 33 radiation oncologists (ROs) and seven medical physicists were trained. The major goals of participating in the master course were to increase confidence in performing brachytherapy and to begin practicing it, as indicated by 23 and 20 responses, respectively. Nine ROs were already doing the BT for HNC, 18 participants were willing to start HN BT procedure within 1year from the training course and five participants did not have the necessary equipment in the postcourse evaluation, 95% and 94% of participants acknowledged adequate coverage of the scope of the topic and the clarity of the content, respectively, as very good or good (5 or 4) in a scale of 5. The training course met the expectation of 94% of the participants. The hands-on training on cadavers for buccal mucosa cancer was considered as very good by 96% of participants and was most useful and needed. One participant insisted on the lacuna of systematic training program for BT in India. CONCLUSIONS:Didactic training with hands-on procedure led to increase in confidence and appears to be one of the suitable methods for training HN BT.

BACKGROUND:Second Primary Malignancies (SPMs) are a common cause of morbidity and mortality in Head & Neck Squamous Carcinoma (HNSCC). Prospective data on incidence, outcomes and prognostic factors is sparse. The current publication summarizes data on 83 SPMs which developed on follow up among patients accrued on a Phase III Randomized Controlled Trial testing treatment intensification in Oral Cavity Squamous Carcinoma (OSCC). PATIENTS AND METHODS:Nine hundred patients of OSCC accrued between 2005-2013 were followed up as part of the trial protocol. Standard clinical criteria were used to determine SPM occurrence. Clinicopathological and demographic variables were summarized using descriptive statistics and analysed using measures of central tendency and dispersion. Outcomes of interest included Overall-Survival (OS) and Progression-Free-Survival (PFS) post SPM diagnosis and were analysed using the Kaplan-Meier method and factors of prognostic significance were compared using the log-rank test and multivariate analysis thereafter. RESULTS:The median follow-up of surviving patients was 95.9 months {(IQR) = 76.1-122.4 months}. A total of 83 SPMs were detected at a median time-to-occurrence of 48 months (IQR-20-87 months) (Cumulative Incidence -11 % at 5 years). The Head & Neck was the most common site of SPM. The 2-year Kaplan Meier estimates of OS and PFS post diagnosis of SPM were 30.3 % (95 %CI-20.9 %-43.9 %) and 21.6 % (95 %CI-13.8 %-34 %) respectively. Multivariate analysis revealed time-to-development of SPM more than 2 years and surgical management of SPM to be associated with superior PFS. CONCLUSIONS:SPMs can cause major morbidity and mortality in OSCC survivors. Strategies need to be developed to gear towards early detection and aggressive salvage.

This prospective cohort study quantified the biological impact of treatment delay in oral squamous cell carcinoma (OSCC) through tumour kinetics. Between July 2020 and December 2023, 483 patients with treatment-naïve OSCC, Mumbai, underwent two pre-surgery cross-sectional imaging studies at least three weeks apart. Gross tumour volume (GTV) was measured to calculate weekly percentage growth and tumour volume doubling time (TVDT) using the Schwartz exponential model. The median interval between scans was 7.1 weeks (IQR, 5.9–9.4). Median GTV increased from 12.9 cm³ (IQR, 8.1–20.2) to 19.4 cm³ (IQR, 12.3–28.6), a 7.3% median weekly rise corresponding to a TVDT of 7.9 weeks. Tongue tumours grew fastest (9.6% per week; TVDT 6.2 weeks). Stage migration occurred in 30%, leading to more extensive resections in 28%. At 25 months’ median follow-up, 2-year overall survival (OS) and disease-specific survival were 67% and 73%, respectively. Patients with TVDT ≤8 weeks had lower OS (58% vs 74%, p=0.002). On multivariable analysis, TVDT ≤8 weeks, treatment delay >8 weeks, advanced T/N-category, and perineural invasion independently predicted worse outcomes. OSCC doubles in volume within 6–10 weeks, and tumour kinetics offer a quantifiable marker of aggressiveness that should inform scheduling and prognosis.

BACKGROUND:Optimal feeding strategy (Prophylactic vs. Reactive) during Radiation Therapy (RT) for Head and Neck Cancers (HNC) remains to be established. METHODS:This phase III trial randomized (1:1) patients of HNC to prophylactic [nasogastric tube (NGT) placed at least 1 day before RT starting] versus reactive arm (NGT when required). The primary endpoint was the incidence of significant weight loss at 6 months. Secondary endpoints were weight changes, tube duration, dependence, and compliance. RESULTS:Due to high denial rates, the trial was prematurely closed. Eighty-four patients (40-prophylactic, 44-reactive) were analyzed intention-to-treat. Seventeen patients (39%) required a reactive tube insertion. The proportion of patients with significant weight loss at 6 months in the prophylactic versus reactive arms was 13 (32.5%) versus 10 (15.9%), p = 0.44. The median tube duration was 56 days (IQR: 16.5-91) versus 47 days (IQR: 24-59), p = 0.255. CONCLUSION:Our limited analysis found that a reactive NGT should be considered for most HNC patients undergoing RT. TRIAL REGISTRATION:Clinical trials registry of India: CTRI/2020/01/023049.