Prognostic and predictive roles of cancer stem cell markers in head and neck squamous cell carcinoma patients receiving chemoradiotherapy with or without nimotuzumab.

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we present predictive and prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Pretreatment tumour tissues of 404 HPV-negative LA-HNSCCs patients, a subset of-phase 3-randomised study comparing cisplatin-radiation(CRT) and nimotuzumab plus cisplatin-radiation(NCRT) were examined. The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival(PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.63 (0.46-0.88)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.10-0.62); OS: HR (95% CI) = 0.38 (0.19-0.74)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. Bootstrap resampling confirmed the predictive effect of CD44 (Interaction P = 0.015) and CD44v6 (Interaction P = 0.041) for OS. Multivariable Cox analysis revealed an independent negative prognostic role of CD98hc membrane expression for LRC [HR (95% CI) = 0.63(0.39-1.0)] and OS[HR (95% CI) = 0.62 (0.40-0.95)]. CONCLUSIONS: CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).

Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab.

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42-0.93)], LRC [HR (95% CI) = 0.56 (0.37-0.86)] and OS [HR (95% CI) = 0.63 (0.43-0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37-0.82), LRC:HR (95% CI) = 0.55 (0.36-0.85) and OS:HR (95% CI) = 0.54 (0.36-0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008). CONCLUSIONS: High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).

The role of chemotherapy in patients with small cell lung cancer and poor performance status.

BACKGROUND: There are limited data on the role of chemotherapy in patients with small cell lung cancer (SCLC) and poor performance status (PS). METHODS: This was a retrospective analysis of a prospective observational study in patients with SCLC and PS 3 or 4. We recorded the initial therapy, symptom improvement, response rate, overall survival (OS), and the impact of various factors on OS. RESULTS: From June 2010 to August 2019, we enrolled 234 patients; 185 (79%) with PS 3 and 49 (21%) PS 4. Initial therapy was best supportive care (BSC) in 49 patients (21%), standard full dose chemotherapy in 31 (13%), and attenuated chemotherapy in 154 (66%). In 89% patients treated with attenuated chemotherapy, symptom-relief occurred at a median of 3 days (IQR, 1-7). Grade 3 and higher toxicities developed in 60% patients treated with initial attenuated chemotherapy, commonly hyponatremia in 39%, neutropenia in 16%, anemia in 11%, and infection in 10%. Grade 3 and higher toxicities as a result of standard chemotherapy occurred in 89% patients treated with upfront standard full dose chemotherapy compared to 69% of patients who received initial attenuated chemotherapy with subsequent treatment escalation. Overall, there were 6 (2.6%) toxic deaths. The response rate to chemotherapy was 77%. The median OS of the patients who received any chemotherapy was significantly longer at 6 months (95% CI, 4.8-7.2) compared to 1 month (95% CI, 0.4-1.6 months) in patients who were managed with BSC, p < 0.001; hazard ratio, 0.39 (95% CI, 0.27-0.56). The disease stage, lactate dehydrogenase level, and receipt of chemotherapy significantly impacted survival. CONCLUSION: Chemotherapy prolongs survival in patients with SCLC and poor PS. Administering an initial attenuated chemotherapy regimen followed by standard full-dose chemotherapy when the PS improves may lower toxicity and improve tolerance.

A Study to Assess the Feasibility of Introducing Early Palliative Care in Ambulatory Patients with Advanced Lung Cancer.

PURPOSE: Early palliative care is beneficial in advanced lung cancer patients. We aimed to assess the feasibility of introducing early palliative care in ambulatory advanced lung cancer patients in an Indian tertiary cancer center. METHODOLOGY: In a longitudinal, single-arm, and single-center study, fifty patients were recruited and followed up every 3-4 weeks for 6 months, measuring the symptom burden using Edmonton Symptom Assessment Scale (ESAS) and quality of life (QoL) with European Organization for Research and Treatment of Cancer-QoL tools. The primary end point of feasibility was that at least 60% of the patients should complete 50% of the planned palliative care visits and over 50% of the patients should complete QoL questionnaires. Analysis was done using Statistical Package for the Social Sciences version 20. RESULTS: Twenty-four of fifty patients (48%) completed the planned follow-up visits. All patients completed the questionnaires at baseline and 31 (62%) at their follow-up visits. The patients' main reasons for not following up in the hospital palliative care clinic were logistics and fatigue. Tiredness, pain, and appetite loss were the highest rated symptoms at baseline (ESAS scores 3, 2.2, and 2.1, respectively). Improvement in pain and anxiety scores at follow-up visits 1 and 2 was significant (P < 0.05). Scores on QoL functioning scales improved during the follow-up period. CONCLUSIONS: We did not meet the feasibility criteria for the introduction of early palliative care in our advanced lung cancer patients in a resource-limited country.

Preoperative Chemotherapy and Metronomic Scheduling of Chemotherapy in Locally Advanced Oral Cancers.

Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral cancers. Preoperative chemotherapy has failed its expectations to improve disease-free survival or overall survival in resectable oral cancers. Its use as an organ preservation tool is being studied. Induction chemotherapy followed by assessment for surgery is an appropriate option for borderline resectable or technically unresectable oral cancer. Metronomic chemotherapy is being studied as a bridge to surgery and as adjuvant chemotherapy in locally advanced oral cancers. The role of induction chemotherapy in unresectable oral cancers is unproven. Metronomic chemotherapy has shown improved progression-free survival and overall survival in oral cancers in comparison to intravenous cisplatin. A phase 3 study for confirmation of this finding has begun.

Aggressive Surgery in Palliative Setting of Lung Cancer: Is it Helpful?

With increase in survival and progression-free survival in the advanced metastatic cancers, the expectation of quality of life (QOL) has increased dramatically. Palliative care plays a vital role in the management of these advanced cancer patients. At present scenario, palliative care in advanced cancer has seen a completely different approach. Aggressive surgical procedures have been performed to improve the QOL in the advanced cancer patients. We report a case of advanced lung cancer with pathological femur fracture, treated with extensive total femur replacement surgery to provide better QOL.

Burden and outcomes of pressure ulcers in cancer patients receiving the kerala model of home based palliative care in India: results from a prospective observational study.

AIM: To report the prevalence and outcomes of pressure ulcers (PU) seen in a cohort of cancer patients requiring home-based palliative care. MATERIALS AND METHODS: All patients referred for home care were eligible for this prospective observational study, provided they were living within a distance of 35 km from the institute and gave informed consent. During each visit, caregivers were trained and educated for providing nursing care for the patient. Dressing material for PU care was provided to all patients free of cost and care methods were demonstrated. Factors influencing the occurrence and healing of PUs were analyzed using logistic regression. Duration for healing of PU was calculated using the Kaplan Meier method. P < 0.05 are taken as significant. RESULTS: Twenty-one of 108 (19.4%) enrolled patients had PU at the start of homecare services. None of the patients developed new PU during the course of home care. Complete healing of PU was seen in 9 (42.9%) patients. The median duration for healing of PU was found to be 56 days. Median expenditure incurred in patients with PU was Rs. 2323.40 with a median daily expenditure of Rs. 77.56. CONCLUSIONS: The present model of homecare service delivery was found to be effective in the prevention and management of PUs. The high prevalence of PU in this cohort indicates a need for greater awareness for this complication. CLINICAL TRIAL REGISTRY NUMBER: CTRI/2014/03/004477.

Real-world analysis of the use of lenvatinib in differentiated thyroid cancers.

Introduction: Lenvatinib is one of the approved treatments for radioiodine-refractory differentiated thyroid cancers. However, there is very limited data from India on real-world efficacy and adverse events of Lenvatinib and hence this analysis was performed. Methods: This was a retrospective analysis in which patients of radioiodine-refractory differentiated thyroid cancer as per the SELECT study criteria, who received lenvatinib, were selected for the study over the last 4 years. The baseline demographic characteristics, adverse events of lenvatinib, the date of progression and the date of overall survival (OS) were extracted from the electronic medical records of Tata Memorial Hospital. SPSS version 20 was used for analysis. Results: The median starting dose of lenvatinib was 20 mg. Fifteen events for progression had occurred and the median progression-free survival (PFS) was 12.2 months [95% CI: 4.4-not available (NA)]. The events for OS analysis were 12. The median OS was 35.3 months (95% CI: 11.4-NA). There was no impact on starting dose on PFS or OS. Conclusion: The real-world data of Lenvatinib suggest a lot of variability in the starting dose. In spite of this variability, the response rates and OS are similar to that noted in pivotal study. This suggests a case for need for more studies evaluating lower doses of Lenvatinib.

Neoadjuvant chemotherapy in a rare type of very locally advanced sinonasal carcinomas - long-term results from a tertiary care centre.

Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.

Real world data on long term outcome of neoadjuvant chemotherapy in locally advanced esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation - Results from a single centre study.

INTRODUCTION: Esthesioneuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are the most common histological subtypes of non-squamous Sinonasal Tumors. A multidisciplinary approach is preferred for locally advanced unresectable esthesioneuroblastoma and SNEC. METHODS: From June 2010 to October 2021, 59 patients with esthesioneuroblastoma and SNEC received NACT. NACT consists of 2-3 cycles of Etoposide-Platinum based chemotherapy. Depending upon response and performance status, subsequent therapy was planned. SPSS descriptive statistics were performed for analysis. Kaplan Meir methods were used for the estimation of Progression Free Survival (PFS) and Overall Survival (OS). RESULTS: 45 (76.3 %) Esthesioneuroblastoma and 14 (23.7 %) SNEC patients received NACT. The median age of the population was 45 years (range 20-81 years). The majority of patients received 2-3 cycles of Platinum (Cisplatin or Carboplatin) + Etoposide as NACT. 28 patients (47.5%) underwent surgery and 20 patients (33.9%) received definitive chemoradiotherapy after NACT. The most common grade 3 or above adverse events were anemia (13.6%), neutropenia (27.1), and hyponatremia (45.8%). At the time of analysis, the median PFS was 56 months (95% CI 31 months to 77 months), and the median OS was 70 months (95% CI 56 months to 86 months). The most common late toxicities noticed were metabolic syndrome (42.4%), hyperglycemia (39%), nasal bleeding (33.9%), hypertension (17%), dyslipidemia (8.5%), and hypothyroidism (5.1%). CONCLUSION: The study shows that NACT is safe, and can be easily delivered without any life-threatening toxicities, with a favorable response and improved survival in this subset of patients.

Association of Immune-Related Adverse Effects and Survival in Solid Tumor Patients Treated with PD1 Inhibitors.

Kumar PrabhashBackground The development of immune-related adverse effects (irAEs) can corroborate with the response to immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD1) inhibitors. However, there is extremely limited data on the association of irAEs with survival in patients who have shown a response to ICIs. Patients and Methods This study is a retrospective audit of the prospectively collected database of patients who received PD1 inhibitors for advanced solid tumors. Responders were defined as patients who attained the best response of either complete response or partial response. Time-to-event analysis was done using the Kaplan-Meier estimator, and the hazard ratio (HR) was calculated by using Cox proportional model. A point-biserial correlation was used to find out the potential influence of irAEs on overall survival (OS). Results A total of 155 patients (49% lung cancer, 31% head and neck cancer) who received ICI during the specified period were evaluated for this study. The overall response rate was 19.4% and disease control rate was 43.2%. The median (OS) for patients who developed irAE was 12.3 months (95% confidence interval [CI]: 8.9-15.6), while it was not reached for patients without irAE (HR: 10.5, 95% CI: 1.2-NR, p = 0.007). One-year OS for the corresponding group of patients was 53.6% (standard deviation [SD]: 15.6) versus 92.9% (SD: 6.9), respectively. Among responders, 12 (40%) developed at least grade 1 irAE, while among nonresponders, 38 (30.4%) developed irAE ( p = 0.312). Conclusions In our study, we found significant improvement in survival of solid tumor patients treated with ICIs who developed irAEs on treatment as compared with those who did not. On specifically analyzing patients who responded to ICIs, there was no difference in OS who developed irAEs versus those who did not. However, this needs to be studied in a larger sample to reach a definite conclusion.

Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer: A Retrospective Review.

Akhil KapoorIntroduction The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also depends on baseline metastatic sites number as well as location with liver metastases being a poor prognostic factor. However, the clinical and prognostic association of baseline liver metastases in ALK fusion-positive mNSCLC is not well known. Material and Methods We performed a retrospective analysis of ALK fusion-positive mNSCLC patients to assess prognostic impact of liver metastases. Records were obtained from lung cancer audit database and electronic medical records. Patients were started on either chemotherapy, ALK-directed tyrosine kinase inhibitors, or given best supportive care as per the clinical scenario. Radiological response was assessed every 2 to 3 months or earlier at clinical suspicion of progressive disease. Adverse events were evaluated as per Common Terminology Criteria for Adverse Events v4.02. Results A total of 441 patients were screened, out of which 76 had baseline liver metastases. Median age was 49 years with 64.5% males. Median progression-free survival (mPFS) was 14.2 months (95% confidence interval [CI] 8.9-19.4) in patients with baseline liver metastases. In patients who received first-line ALK inhibitor therapy versus who received first-line chemotherapy, mPFS was significantly better in the ALK-directed therapy subgroup, 15.3 months (95% CI 11.7-18.9) versus 5.9 months (95% CI 2.7-9.1), respectively (hazard ratio [HR] 0.3 [95% CI 0.17-0.54]; p < 0.001). Median overall survival (mOS) was 27.6 months (95% CI 17.4-37.7) in patients with baseline liver metastases which was not statistically significant from patients without baseline liver metastases which was 32.3 months (95% CI 28.8-35.7) (HR 1.32 [95% CI 0.91-1.9]; p = 0.22). Use of ALK-directed therapy in patients with baseline liver metastases resulted in better OS, mOS not reached versus 15.7 months (95% CI 2.7-28.8) in the chemotherapy group (HR 0.33 [95% CI 0.16-0.67]; p < 0.001). Conclusion In patients with ALK fusion-positive mNSCLC, baseline liver metastases was not found to be an independent prognostic factor. However, the use of ALK-directed therapy resulted in a significantly better PFS and OS as compared with chemotherapy in patients with baseline liver metastases. This underscores the importance of the use of ALK-directed therapy whenever feasible in this group of patients.

Caregiver burden in older Indian patients with cancer- Experience from a tertiary care center.

INTRODUCTION: Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer. MATERIALS AND METHODS: This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis. RESULTS: Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60-90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6-20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level. DISCUSSION: Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden.

Audit of screen failure in 15 randomised studies from a low and middle-income country.

Background: Growth and development in patient management occurs via randomised studies. Screen failure is a significant hurdle while conducting randomised studies. There is limited data available from low and middle-income countries about factors resulting in screen failure. Hence, this audit was performed to identify the proportion of patients who screen failed and to elucidate reasons for the same. Methods: This was an audit of 15 randomised studies performed by medical oncology solid tumour unit II of Tata Memorial Centre. The screening logs of these studies were acquired. From the screening logs, data regarding the number of patients who had screen failed & reason for the same were obtained. Descriptive statistics were performed. Results: A total of 7,481 patients were screened for 15 randomised clinical studies. Out of these, 3,666 (49.0%) patients were enrolled into trials and 3,815 (51.0%) screen failed. The most common reason for screen failure was 'not meeting inclusion criteria' (54.9%) followed by declining to take treatment (22.2%). Other factors that affect enrolment were 'not willing to stay in the locality of the trial site' (6.2%), being recruited in other studies (3.7%), poor performance status (PS) (3.4%), non-compliance (2.2%), meeting exclusion criteria (0.9%) and 'other' (6.5%). Conclusion: The commonest causes of screen failure in lower and middle-income countries are non-meeting of inclusion criteria followed by declining to take treatment, not willing to stay in locality of trial site, recruited into other studies, poor PS, non-compliance, meeting exclusion criteria & 'other'. This information would help analysing and hence planning of newer strategies to decrease the rate of screen failure.

An Audit of Systemic Therapy in Medullary Carcinoma Thyroid.

There is a paucity of evidence of the impact of sorafenib on MCT and it is the preferred therapy used in India. We decided to do an audit of all patients of MCT who were referred to us for systemic therapy. The objective of this exercise was to identify the treatment pattern, outcomes, and adverse events with therapy in MCT. Baseline demographics (age, gender, ECOG PS, comorbidities, habits), tumor details (site of metastasis), previous treatment details, clinical features at metastasis (symptomatic or asymptomatic), the pattern of treatment, adverse events (CTCAE version 4.02), date of progression, date of death and status, and follow-up were extracted from the rare tumor database and electronic medical records. Out of 75 patients referred for therapy for MCT, 47 (62.7%) patients were considered for immediate tyrosine kinase inhibitors as they had symptomatic status and 28 (37.3%) patients were kept on observation due to the asymptomatic nature of the disease. Out of the 28 patients, 15 (53.6%, n = 28) patients were subsequently started on TKI while in 13 (46.4%, n = 28) patients observation was continued. In the overall cohort, the median PFS was 18.9 months (95% CI 11.9-29.9) and OS was 26.6 months (95% CI 14.4-39.0). Among variables tested, only female gender had an impact on PFS (hazard ratio = 0.364 95% CI 0.148-0.895; P = 0.028) and the absence of lung metastasis had a positive impact on OS (hazard ratio = 0.443 95% CI 0.207-0.95; P = 0.037). Most commonly used TKI was sorafenib (n = 61) and sunitinib in 1 patient. The most common adverse events with TKI were palmo-plantar dysesthesia (50, 80.6%) and oral mucositis (25, 40.2%). The strategy of treating symptomatic MCT and observing in asymptomatic MCT is associated with reasonable PFS and OS. Sorafenib is the most commonly used TKI in our setup and provides similar outcomes as globally.

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial.

Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) has activity in glioma both in-vivo and in-vitro, and is well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: In this phase II randomized open-label trial, adult patients with ECOG PS 0-3, with recurrent GBM who were not eligible for re-radiation, were randomized 1:1 to the CCNU-MBZ and TMZ-MBZ arms. CCNU was administered at 110 mg/m2 every 6 weeks with MBZ 800 mg thrice daily and TMZ was administered at 200 mg/m2 once daily on days 1-5 of a 28 days cycle with MBZ 1600 mg thrice daily. The primary endpoint was OS at 9 months. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. OS was analyzed using intention to treat (ITT) and per-protocol (PP) analyses. Per-protocol analysis was used for safety analysis. Clinical Trials Registry-India number, CTRI/2018/01/011542. Findings: Participants were recruited from 14th March 2019 to 18th June 2021, 44 patients were randomised on each arm. At 17.4 months, 68 events for OS analysis had occurred, 33 in the TMZ-MBZ and 35 in the CCNU-MBZ arm. The 9-month OS was 36.6% (95% CI 22.3-51.0) and 45% (95% CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively, in the ITT population. ECOG PS was the only independent prognostic factor impacting OS (HR-0.48, 95% CI 0.27-0.85; P = 0.012). Grade 3-5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. There were no treatment related deaths. Interpretation: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients having poor PS of 2-3. Funding: Brain Tumor Foundation (BTF) of India, Indian Cooperative Oncology Network (ICON), and India Cancer Research Consortium (ICRC) under ICMR (Indian Council of Medical Research).

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings.

ABSTRACT: Immune checkpoint inhibitors (ICIs) are rapidly being incorporated as treatment option either alone or in combination with chemotherapy in most of the solid tumors. Since there is very limited data of ICI in patients with poor performance status (PS) from the real world settings, we performed a retrospective audit of patients who received ICI and report the analysis based on ECOG PS of these patients.This study is a retrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. All statistical calculations were performed using SPSS statistical software for windows version 20.0.A total of 155 patients who received ICIs during the specified period were evaluated for this study. Baseline ECOG PS 0-1 (n = 103, 66.4%) patients was associated with median OS 9.1 (95% CI [confidence interval], 4.4-NR) months when compared to ECOG 2-4 (n = 52, 33.5%) which had a median OS of 2.9 (95% CI; 1.8-5.5) months (HR, 1.7, 95% CI, 1.1-2.7, log rank P = .017). The disease control rate for the poor PS group was 34.6%. However, 27.3% patients (95% CI: 20.3-34.3) were still alive at 1 year. Median OS in patients with PS 2 was 3.7 months (95% CI: 0-11.6) as compared to 1.8 months (95% CI: 0.2-3.4) for those with PS 3-4 (HR-2.0; 95% CI: 1.0-3.9, P = .041). The tolerance to ICIs was good with no grade 3/4 toxicities in 44 (84.6%) patients.Immune checkpoint inhibitors are a safe and effective therapeutic option even in solid tumor patients with poor performance status.

Weight loss and its impact on outcome in head and cancer patients during chemo-radiation.

BACKGROUND: Weight loss during chemotherapy and its impact on the cancer outcomes have been invariably reported in the literature. We also did a post-hoc analysis of a randomized phase III trial to see the same. MATERIALS AND METHODS: The database of a recently published randomized study comparing cisplatin-radiation with nimotuzumab cisplatin-radiation was used for this analysis. Week-wise weight loss during the course of treatment was noted. The impact of severe weight loss (grade 2-3) on progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) was studied using the Kaplan Meier method. Binary logistic regression analysis was used to see the effect of various factors. RESULTS: Out of a total of 536 patients, weight loss was captured in 524. Out of these 524 patients, any degree of weight loss was seen in 293 (55.91%) patients. Grade 1 weight loss was noted in 192 (36.6%) patients, grade 2 in 96 (18.3%) and grade 3 in 5 (1%) patients. The 2-year PFS was 53% and 57.1% in severe and non-severe weight loss groups respectively (p-value = 0.36). The 2-year LRC was 60% in patients with severe weight loss, while it was 63.5% in those with non-severe weight loss (p-value = 0.47). The 2-year OS was 59.3% versus 62.2% in severe and non-severe weight loss cohorts respectively (p-value = 0.21). None of the factors was found to be associated with severe weight loss. CONCLUSION: Severe weight loss was uncommon in our patients. Weight loss during treatment was not associated with poor survival outcomes.

Post hoc analysis of a randomized controlled trial comparing concurrent chemoradiation with cisplatin versus nimotuzumab-cisplatin, focusing on acute oral mucositis.

BACKGROUND: Acute oral mucositis has been infrequently studied in the patients with head and neck squamous cell carcinoma (HNSCC) receiving once-weekly cisplatin-based chemoradiotherapy (CRT). Hence, this analysis was conducted to explore the various aspects of the same. RESULTS: The overall incidence of mucositis was 96.9% (n = 508) and of grade 3-5 mucositis was 61.3% (n = 321). The overall incidence of oral mucositis was similar in both the arms (CCRT and NCRT) (p value = 0.58) while grade 3-5 mucositis was more common in the NCRT arm (p value = 0.01). Out of all factors listed, the presence of nimotuzumab was the only significant risk factor for the development of grade 3 or more oral mucositis (p value = 0.01); (OR = 1.64, 95%CI 1.15-2.32). Delays in the treatment delivery were similar in both the arms. CONCLUSION: Acute oral mucositis is a common occurrence in locally advanced-HNSCC patients receiving chemoradiotherapy. Nimotuzumab is a significant factor for development of grade 3 and above oral mucositis.