Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.

A Comparative Study Evaluating the Quality of Life and Survival Outcomes in Patients Receiving Chemotherapy Versus Oral Tyrosine Kinase Inhibitor in the Third Line and Beyond Setting for Advanced NSCLC.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was -28 in the chemotherapy arm and -26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04-137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15-4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1-2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83-1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96-9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85-9.14); hazard ratio at 1.033 (95% CI: 0.80-1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.

PURPOSE: The purpose of this study was to understand the impact of population diversity and geographic variation on tumor mutation burden (TMB) scores across cancers and its implication on stratification of patients for immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: This retrospective study used whole-exome sequencing (WES) to profile 1,233 Indian patients with cancer across 30 different cancer types and to estimate their TMB scores. A WES-based pipeline was adopted, along with an indigenously developed strategy for arriving at true somatic mutations. A robust unsupervised machine learning approach was used to understand the distribution of TMB scores across different populations and within the population. RESULTS: The results of the study showed a biphasic distribution of TMB scores in most cancers, with different threshold scores across cancer types. Patients with cancer in India had higher TMB scores compared with the Caucasian patients. We also observed that the TMB score value at 90th percentile (predicting high efficacy to ICI) was high in four different cancer types (sarcoma, ovary, head and neck, and breast) in the Indian cohort as compared with The Cancer Genome Atlas or public cohort. However, in lung and colorectal cancers, the TMB score distribution was similar between the two population cohorts. CONCLUSION: The findings of this study indicate that it is crucial to benchmark both cancer-specific and population-specific TMB distributions to establish a TMB threshold for each cancer in various populations. Additional prospective studies on much larger population across different cancers are warranted to validate this observation to become the standard of care.

Real-World Evidence of EGFR Targeted Therapy in NSCLC- A Brief Report of Decade Long Single Center Experience.

The significance of EGFR targeted therapy in the lung adenocarcinoma is paramount. Several controlled clinical trials have reported considerable survival of EGFR mutation positive patients on receiving the EGFR tyrosine kinase inhibitor (TKI). However, the real-world evidence of benefits of EGFR TKI would be further useful to understand how the designated therapeutic regimen benefits the patients. In this study, we report a decade long real-world evidence of EGFR molecular testing in lung cancer at Tata Memorial Hospital (Mumbai, India). Laboratory and hospital records containing basic demographic details, clinical characteristics, treatment regimen, survival outcome were collected retrospectively. Statistical association and survival analysis were performed using the R programming. The cohort includes 9,053 lung cancer patients tested for EGFR mutations during 2011 to 2019. Baseline T790M and compound mutations were the only mutations observed co-occurring while all other EGFR mutations were mutually exclusive. Furthermore, the baseline T790M were also observed to be associated with TTF1 positivity, smoking and local metastasis. Overall survival of the patients harboring co-occurring compound mutations was significantly lesser than the other EGFR positive patients. Overall, our study suggests that EGFR TKI may provide real-world benefit to the lung cancer patients harboring mutually exclusive EGFR mutations. On the other hand, further systematic study is essential to develop better therapeutic regimen for co-occurring baseline EGFR T790M and other compound mutations.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.

PURPOSE: The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS: This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS: One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744). CONCLUSION: To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.

Characteristics and clinical outcomes of pulmonary sarcomatoid carcinoma: experience from Tata Memorial Centre.

Background: Pulmonary sarcomatoid carcinoma (PSC) constitutes a heterogeneous group of poorly differentiated non-small cell lung cancers. Since these are rare tumours, we sought to determine the characteristics and clinical outcomes of these patients treated at our centre. Methods: We did a retrospective evaluation of all patients diagnosed with PSC between January 2013 and September 2020 at the Tata Memorial Hospital, Mumbai, India. Baseline demographic and treatment data and outcomes were obtained retrospectively from electronic medical records and survival was calculated by using the Kaplan-Meier method. Results: Out of 151 patients diagnosed with PSC during this period, 129 were included in the final analysis. The clinical stage was stage I in 3 (2.03%), stage II in 4 (3.1%), stage III in 35 (27.1%) and stage IV in 87 (67.4%). The median follow-up duration was 32 months (range, 15.0-48.9). The median overall survival (OS) of patients who received curative surgery was 18 months (95% confidence interval (95% CI), 2.59-33.4); concurrent chemoradiation was 11 months (95% CI, 2.99-19); palliative chemotherapy was 8 months (95% CI, 5.24-10.75) and best supportive care was 1 month (95% CI, 0.43-1.57, p = 0.001). On multivariate analysis, the presence of brain metastasis (p = 0.018; hazard ratio (HR), 2.47; 95% CI, 1.34-4.49) and the administration of chemotherapy (p = 0.037; HR, 2.2; 95% CI, 1.04-4.94) were the only factors impacting the OS. Conclusion: PSC usually presents in advanced stages and is associated with a poor prognosis.

Clinical Utility of Liquid Biopsy (Cell-free DNA) Based EGFR Mutation Detection Post treatment Initiation as a Disease Monitoring Tool in Patients With Advanced EGFR-mutant NSCLC.

INTRODUCTION: Plasma cfDNA-based mutation analysis has shown disease-monitoring potential in various cancers. We assessed the potential of cfDNA-based EGFR mutation testing as a monitoring tool in patients with NSCLC. PATIENTS AND METHODS: Patients with NSCLC harboring EGFR mutations receiving first-line treatment as per institutional protocol were enrolled. EGFR mutation status was determined using plasma samples at baseline and post treatment initiation. Patients in whom EGFR mutation was detected or persisted after treatment initiation were considered circulating tumor DNA (ctDNA)-positive. Progression-free survival (PFS) and overall survival (OS) for ctDNA-positive and negative patients post treatment initiation were the primary endpoints; concordance for baseline EGFR status between tissue and plasma and proportion of patients who were ctDNA-positive post treatment initiation were the secondary endpoints. RESULTS: We enrolled 158 patients; 76 received gefitinib, and 82 received gefitinib plus chemotherapy. Median follow-up duration was 42 months. About 25% of patients were ctDNA-positive post treatment initiation. Median PFS for ctDNA-negative patients post treatment initiation was 14 (95% confidence interval [CI], 12.0-17.0) months, while that for ctDNA-positive patients was 8 (95% CI, 6.0-10.0) months. Median OS for ctDNA-negative patients post treatment initiation was 27 (95% CI, 24.0-32.0) months, while that for ctDNA-positive patients was 15 (95% CI, 11.0-19.0) months. Concordance at baseline between tissue and plasma samples was 75.4%. CONCLUSION: Plasma-based EGFR mutation detection post treatment initiation can be used as a predictive marker for outcome in patients with EGFR-mutant NSCLC receiving first-line treatment.

Audit of Demographics, Treatment Patterns and Outcomes of Differentiated Thyroid Cancers Treated with Tyrosine Kinase Inhibitors.

The real-world patterns of TKI use in differentiated thyroid cancer (DTC) are largely governed by the accessibility and financial feasibility of the patient with more sorafenib use compared to lenvatinib. There are limited data available on the toxicity profile, safety and tolerance of sorafenib and lenvatinib in DTC. Hence, we audited our practice on DTC. This is a retrospective single-centre analysis of patients with DTC who were referred to the Department of Medical Oncology for systemic therapy. Baseline demographics (age, sex, ECOG PS, comorbidities, substance use), tumour details (site of metastasis), previous treatment details, clinical features at metastasis (symptoms), the pattern of treatment, adverse events and outcomes including progression and death were extracted. There were 67 patients with DTC referred for systemic therapy; the median age was 56 (33-81) with a male preponderance (55.6%). The most common reason to start TKI therapy was radioactive iodine (RAI) cumulative dose > 600 milliCurie, followed by low iodine uptake in the RAI low-dose scan done at progression. The most common TKI used in the first line was sorafenib in 56 (83.6%) patients followed by lenvatinib in 9 (13.4%) patients. Papillary thyroid carcinoma was the most common histology (51, 76.1%), and the rest were follicular carcinoma (16, 23.9%). With a median follow-up of 36 months, the median PFS was 13.2 months (95% CI 10.4-16.0). The median OS was 18.8 months (95% CI 10.0-27.6). Among variables tested, no factors had a significant impact on the PFS or OS. The most common adverse events were hand-foot syndrome (54, 80.5%), diarrhoea (23, 33.3%) and transaminitis (24, 34.4%). The pattern of care of patients with RAI-refractory DTC is TKI therapy, especially sorafenib and lenvatinib in the real-world settings with comparable efficacy and safety profile compared to international literature.

Quality of life in patients with locally advanced head and neck squamous cell carcinoma undergoing concurrent chemoradiation with once-a-week versus once-every-3-weeks cisplatin.

INTRODUCTION: This trial was conducted to compare the efficacy of low dose once-a-week cisplatin and once-every-3-weeks cisplatin with radiation in locally advanced head and neck squamous cell carcinoma (LAHNSCC). The current analysis focuses on the quality of life (QoL) of patients in this trial. METHODS: In this phase III randomized trial, patients with nonmetastatic LAHNSCC were randomized to receive cisplatin 30 mg/m2 once-a-week or 100 mg/m2 once every- 3-weeks concurrently with radiotherapy. The primary endpoint was locoregional control. QoL was a key secondary endpoint. QoL was assessed using EORTC QLQ-C30 and QLQ-H&N35. QoL data were assessed at baseline, days 22 and 43 during treatment; and at 6, 12, 24 months. The linear mixed-effects model was used for longitudinal analysis of QoL to determine the impact of treatment (arm) and time on QoL. RESULTS: Three hundred patients were enrolled, data of 150 patients with available baseline QoL were analyzed. There was no significant difference in the global health status/QoL of the two treatment arms (p = 0.8664). There was no significant difference in the longitudinal QoL scores between the two treatment arms in all scales except constipation (p = 0.0096), less sexuality (p = 0.0002,), and financial difficulty (p = 0.0219). There was a worsening of the QoL scores in all scales in both arms during treatment, which improved after treatment completion in most scales. CONCLUSION: The use of once-every-3-weeks cisplatin did not adversely impact QoL as compared to once-a-week cisplatin in combination with radiotherapy in LAHNSCC.

Prospective Phase II Open-Label Randomized Controlled Trial to Compare Mandibular Preservation in Upfront Surgery With Neoadjuvant Chemotherapy Followed by Surgery in Operable Oral Cavity Cancer.

PURPOSE: The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS: This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS: Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival (P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival (P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION: NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.

Anaplastic Cancer: Our Experience.

Anaplastic thyroid carcinoma (ATC) is a rare thyroid malignancy with a dire prognosis, nearly 100% disease specific mortality and a median overall survival less than 6 months. In view of the limited data from India on anaplastic thyroid cancer, we conducted this audit to analyze the treatment pattern, outcomes and factors influencing it. This is a retrospective analysis of outcomes of patients treated in a single institution between January 2008 and December 2020. Baseline characteristics, treatment received, and outcomes among adult patients with ATC were collected. Progression free survival (PFS) and overall survival (OS) were analyzed. SPSS version 20 and RStudio version 3.1.1 were used for analysis. In this cohort of 134 patients, the median age at diagnosis was 59 years, with 63.4% of them being females. At presentation, 70.9% of them had good performance status (PS 0-1). Only 38.8% received treatment with curative intent (either surgery fb adjuvant or neoadjuvant chemotherapy fb surgery and adjuvant or definitive chemoradiotherapy) while 61.2% patients received palliative treatment (either palliation alone or palliative chemotherapy or palliative surgery or palliative RT). Predominant pattern of progression was local progression (79.8%). Median PFS and OS of the overall cohort were 58 days and 80 days respectively. PFS and OS were significantly better in patients treated with curative intent vs palliative intent (116 and 134 days vs 45 and 50 days; p = 0.00 and 0.00 respectively). Among patients treated with curative intent, OS was significantly better in patients undergoing surgery vs CTRT (155 vs 76 days; p = 0.03). Among patients treated with upfront surgery, both PFS and OS were better with the addition of adjuvant CTRT/RT vs no adjuvant (332 and 540 days vs 55 and 91 days; p = 0.00 and 0.003 respectively). ATC is a rare cancer with dismal prognosis. Local therapy with surgery followed adjuvant seems to be associated with the better outcomes. Systemic therapy seems to be a better option for palliation. Our data reflects the real world data of this rare cancer.

Demographics, Pattern of Care, and Outcome Analysis of Malignant Melanomas - Experience From a Tertiary Cancer Centre in India.

BACKGROUND: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). PATIENTS AND METHODS: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). RESULTS: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. CONCLUSIONS: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

Effect of Early Palliative Care on Quality of Life of Advanced Head and Neck Cancer Patients: A Phase III Trial.

BACKGROUND: Early palliative care (EPC) is an important aspect of cancer management but, to our knowledge, has never been evaluated in patients with head and neck cancer. Hence, we performed this study to determine whether the addition of EPC to standard therapy leads to an improvement in the quality of life (QOL), decrease in symptom burden, and improvement in overall survival. METHODS: Adult patients with squamous cell carcinoma of the head and neck region planned for palliative systemic therapy were allocated 1:1 to either standard systemic therapy without or with comprehensive EPC service referral. Patients were administered the revised Edmonton Symptom Assessment Scale and the Functional Assessment of Cancer Therapy for head and neck cancer (FACT-H&N) questionnaire at baseline and every 1 month thereafter for 3 months. The primary endpoint was a change in the QOL measured at 3 months after random assignment. All statistical tests were 2-sided. RESULTS: Ninety patients were randomly assigned to each arm. There was no statistical difference in the change in the FACT-H&N total score (P = .94), FACT-H&N Trial Outcome Index (P = .95), FACT-general total (P = .84), and Edmonton Symptom Assessment Scale scores at 3 months between the 2 arms. The median overall survival was similar between the 2 arms (hazard ratio for death = 1.01, 95% confidence interval = 0.74 to 1.35). There were 5 in-hospital deaths in both arms (5.6% for both, P = .99). CONCLUSIONS: In this phase III study, the integration of EPC in head and neck cancer patients did not lead to an improvement in the QOL or survival.

Concurrent chemoradiotherapy for locally advanced unresectable adenoid cystic carcinoma of head and neck: experience from a single institute.

PURPOSE: To analyze the outcome of locally advanced unresectable adenoid cystic carcinoma (ACC) of head and neck treated with radical concurrent chemoradiotherapy (CRT) at a single tertiary care centre. METHODS: Between 2011 and 2018, 23 patients with locally advanced unresectable ACC of head and neck treated with non-surgical radical treatment with concurrent chemoradiotherapy were evaluated for outcome and toxicity. All but one patient received cisplatin-based concurrent chemotherapy and 74% of patients were treated with intensity-modulated radiotherapy. RESULTS: Median follow-up was 53 months (range 3-115 months). Following treatment, 11 patients achieved complete response (47.8%) and of the 12 patients with residual disease, 7 patients additionally had disease stabilization without local progression. Overall 15 patients had disease progression. Median time to progression was 28 months (range 6-67 months). The 3-year and 5-year overall survival, local progression-free survival (LPFS) and distant progression-free survival (DPFS) were 78%, 79.7%, 67.4% and 63%, 50.9%, 48.6%, respectively. Acute grade 3 mucositis was observed in three patients, and one patient additionally developed grade 4 neutropenia with subsequent complete recovery. No grade 3 or higher late toxicity was observed. CONCLUSION: Radical concurrent chemoradiotherapy is a promising treatment option in locally advanced unresectable ACC with acceptable toxicity.

Diclofenac versus tramadol for mucositis related pain in head and neck cancer patients undergoing concurrent chemoradiation-a phase 3 study.

BACKGROUND: Oral mucositis related pain during CTRT in head and neck cancers is a common problem. Unfortunately, in spite of it being common, there is limited evidence for selection of systemic analgesic in this situation. Hence, this study was designed to compare the analgesic effect of a non-steroidal anti-inflammatory drug (diclofenac) versus a weak opioid (tramadol). PATIENTS AND METHODS: This was an open-label, parallel design, superiority randomised controlled study. In this study, head and neck cancer patients undergoing radical or adjuvant chemoradiation, who had grade 1 or above mucositis (in accordance with Common Terminology Criteria for Adverse Events version 4.03) and had pain related to it were randomly assigned to either diclofenac or tramadol for mucositis related pain control. The primary endpoint was analgesia after the first dose. The secondary endpoints were the rate of change in analgesic within 1 week, adverse events and quality of life. RESULTS: One hundred and twenty-eight patients were randomised, 66 in diclofenac and 62 in tramadol arm. The median area under the curve for graph of pain across time after first dose of pain medication for the diclofenac arm and the tramadol arm was 348.936 units (range: 113.64-1,969.23) and 420.87 (101.97-1,465.96), respectively, (p = 0.05619). Five patients (8.1%) in the tramadol arm and 11 patients (16.7%) in the diclofenac arm required a change in analgesic within 1 week of starting the analgesic (p = 0.184). There was no statistically significant difference in any adverse events between the two arms. However, the rate of any grade of renal dysfunction was numerically higher in the diclofenac arm (10.6% versus 4.8%, p = 0.326). CONCLUSION: In this phase 3 study, evaluating diclofenac and tramadol for chemoradiation induced mucositis pain, there was no statistical difference in analgesic activity of these two drugs.