e13727 Background: Literature demonstrates that non-actionable biomarkers (BMs) can co-occur with actionable ones in NSCLC and impact patient outcome. Our research sought to examine oncologists’ perspectives on hierarchy of clinical relevance of established and emerging BMs, their decision framework for managing co-occurring BMs, and how it could play out in future when these non-actionable BM become actionable. Methods: Between November-December 2025, 50 US-based Oncologists from a diverse set of practice settings and experience managing patients with metastatic NSCLC were recruited. They completed a 45-minute one-on-one interview where they shared perspective on their BM-informed treatment philosophy – BM prioritization, treatment algorithm over multiple lines of therapy when co-occurring BM are detected, and how they arrived at those beliefs in the present context. Results: Among the oncologists included in the study, 60% practiced in community settings and 40% in academic settings. Across practice types, the primary factors guiding treatment selection were efficacy, safety, alignment with clinical guidelines and FDA approval. Overall, 92% of respondents (45/49) reported that NCCN guidelines were useful for evidence-based decision-making, including 28% (14/49) who found them extremely helpful. Despite this reliance on guidelines, nearly 60% of responders (29/49) indicated that there is no clearly defined protocol for managing co-occurring BM or reported being unfamiliar/uncertain about available guidance. When presented with a clinical scenario involving co-occurring EGFR and TP53 mutation, 28 oncologists shared their perspectives. Approximately half (15/28) reported they would initiate therapy with an anti-TP53 drug followed by EGFR inhibitor, provided the anti-TP53 drug demonstrated ~20% higher efficacy in comparison to 'historical EGFR inhibitor outcomes in patients with co-occurring EGFR and TP53 mutation’, even if the registrational trial for anti-TP53 drug did not give details on patients with co-occurring mutations, or if such patients were excluded from the trial. Remaining oncologists preferred initiating treatment with an EGFR inhibitor and sequencing anti-TP53 therapy upon progression, citing greater familiarity with EGFR-directed treatments. These perspectives were similarly distributed across community and academic practice settings. Conclusions: This study shows that in the absence of clear regulatory or clinical guidance, treatment decisions for patients with co-occurring BMs may vary widely. While clinicians draw on conferences data and published research, this evidence base is insufficient to ensure consistent care. Our findings underscore the need for coordinated action from researchers, regulators and guideline bodies to establish clear standards of care to improve outcomes for patients with BM-complex disease.

PURPOSEAdvanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India.PATIENTS AND METHODSA total of 238 adults with histologically confirmed, unresectable advanced HNSCC eligible for palliative platinum-based chemotherapy were randomly assigned 1:1 after stratification by tumor site and Eastern Cooperative Oncology Group (ECOG) performance status. Arm A received PC plus OMCT; Arm B received PC alone. The primary end point was OS. Secondary end points included progression-free survival (PFS), quality of life (QoL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Functional Assessment of Cancer Therapy—Head & Neck), and safety.RESULTSAmong 238 patients (119 per arm), the median age was 47 years; 97.8% were male, and 78% had ECOG performance status (PS) 0-1. The median OS was 10 months (95% CI, 8.3 to 11.7) with PC + OMCT versus 5 months (95% CI, 3.9 to 6.1) with PC alone (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72]; P < .001). The median PFS was 6 months versus 2 months, respectively (HR, 0.38 [95% CI, 0.28 to 0.50]; P < .001). QoL analyses demonstrated clinically meaningful preservation across multiple domains in the PC + OMCT arm. Grade ≥3 toxicities did not increase with the addition of OMCT.CONCLUSIONIn platinum-sensitive advanced HNSCC, the addition of triple OMCT to PC significantly improved OS and PFS with acceptable toxicity. PC + OMCT represents a feasible and cost-conscious first-line option in resource-constrained settings.

e20080 Background: Lung cancer is the second most common cancer with a high mortality rate. Understanding its genomic landscape is crucial for identifying clinically actionable biomarkers and overcoming therapeutic challenges. This study explores the genomic profile of lung cancer patients from India. Methods: The genomic profiles of 1,266 Indian lung cancer patients in advanced stage of the disease (80% with progression in first/second/third line standard of care), were retrospectively analyzed for SNVs/InDels, CNVs, gene fusions, and immunotherapy biomarkers, including TMB, MSI, and PD-L1 expression. FFPE tumor samples were assessed using NGS-based gene panels and exome sequencing. Results: Clinically significant variants/drivers were identified in 88.7% of the patients. Predominant genomic alterations included SNVs/InDels in TP53 (47.2% of cohort), EGFR (35.7%) and KRAS (4.8%) , gene amplifications in EGFR (2.3%) , MET (0.6%) , CDK4 (0.6%) , and ERBB2 (0.5%) , and ALK--EML4, ROS1 and RET gene fusion. Recurrent mutations included 23.5% in EGFR p.Leu858Arg (12.1%), p.Glu746_Ala750del (11.4%), KRAS p.Gly12Cys (4%) and p.Gly12Asp (2.6%). 15% of EGFR activating mutations were rare category mutations; this further emphasises the clinical benefit of CGP over hotspot panels. EGFR exon 20 insertions were seen in 1.5% of the cohort and ERBB2 mutations were seen in 3.6%. Variants associated with acquired resistance to TKI therapy were identified in 9.5% of the patients, with 5.5% harboring multiple co-occurring resistance variants. Clustering co-mutations identified targetable co-occurring variants AKT1 , KRAS and PIK3CA in patients where EGFR variants were the primary driver in 35.7% of the patients. Clinically actionable genomic alterations were detected in 84% of the cohort, which included 50% patients eligible for FDA approved therapies, 2.7% eligible for off-label therapies and 31.2% were eligible for therapies in clinical trials. High TMB (>10 mut/Mb) was observed in 7.7% of patients, MSI-H in 2.4% of patients and PDL1 expression (>1%) was noted in 9.2% of patients. Conclusions: 80% of the NSCLC patients opted for broad NGS panel after failure of first/second- or third-line standard of care therapy. Our study provides insights into the genomic landscape of lung cancer in India and highlights the utility of CGP in identifying clinically significant drivers and therapeutic biomarkers with implications in prognosis and therapy response in the routine clinical practice. Mutated genes targeted by FDA approved drugs (Level 1) Mutated genes targeted by off-label therapy (Level 2) EGFR (SNV & gene amplification) (Tier 1 AMP) ALK gene fusion (Tier 1 AMP) MAP2K1 BRCA2 (Tier 1 AMP) RET gene fusion (Tier 1 AMP) BRAF (Tier 1 AMP) ROS1 gene fusion (Tier 1 AMP) BRCA1 (Tier 1 AMP) RET gene fusion (Tier 1 AMP) MET (Tier 1 AMP) FGFR3 gene fusion (Tier 2 AMP) ERBB2 (SNV & gene amplification) (Tier 1 AMP) NTRK1 gene fusion

Background:Colorectal cancer (CRC) is one of the most common malignancies across the world and is the fourth most common cancer among men in India as per the Global Cancer Observatory (GLOBOCAN) data 2020. Available data suggest that approximately 30% of patients present with advanced/metastatic CRC (mCRC). This publication summarizes the latest evidence with cognizance of the unique challenges faced in India by medical oncologists treating mCRC. Methods:A panel of 38 medical oncologists held a meeting in February 2023 and reviewed the evidence available for the management of mCRC. The meeting concentrated on the recognition and management of mCRC with a focus on systemic therapeutic approaches. A literature review of these aspects of management leads to the formation of consensus statements with the level of evidence and grades of recommendation. Statements were evaluated by the modified Delphi method. Key Content and Findings:The panel comprising 38 experts formulated 51 consensus statements with regard to the management of mCRC, including oligometastatic CRC, unresectable CRC, as well as various systemic therapeutic options. Resource-constrained scenarios, specifically with regard to the economic constraints and availability of drugs in India, were evaluated as part of the statements. Conclusion:Our consensus statements offer practical, yet evidence-based management guidelines for treating mCRC in the Indian context. Stratifying and recommending treatment options in a resource-constrained scenario is an important aspect of these statements.

HER2-positive metastatic breast cancer (MBC) represents a challenging subtype of breast cancer, characterized by aggressive disease and poor clinical outcomes. Trastuzumab emtansine (TDM1), an antibody-drug conjugate combining trastuzumab and emtansine, has demonstrated efficacy in clinical trials as a second-line treatment for patients progressing after prior therapies. This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients. A retrospective analysis was conducted on 70 HER2-positive MBC patients treated with TDM1 at our centre between January 2020 and December 2022. Clinical characteristics, progression-free survival (PFS), overall survival (OS), response rates, and toxicity were evaluated using hospital records. PFS and OS were calculated using Kaplan-Meier methods, and survival curves were compared with log-rank tests. The median age of patients was 47 years, with a majority presenting with advanced disease and prior treatment lines. The median PFS was 6.1 months (95% CI, 4.5-7.6), and the median OS was 14.4 months (95% CI, 10.2-18.0). The objective response rate was 75.7%, with 12.8% achieving a complete response and 62.8% a partial response. PFS was significantly longer in hormone receptor-positive patients compared to hormone receptor-negative patients (8.1 vs. 4.1 months, p = 0.035). Toxicity was manageable, with grade 3-4 adverse events including elevated transaminases (8.5%), thrombocytopenia (5.7%), and anemia (4.2%). The efficacy of TDM1 in this real-world cohort aligns with clinical trial data, though PFS and OS were somewhat lower compared to trials, likely due to the inclusion of patients with more extensive disease and prior treatments. Notably, TDM1 demonstrated activity against CNS metastases and a manageable safety profile, with higher incidence of hepatic and hematologic toxicities. Our study supports the use of TDM1 as a viable option for treating HER2-positive MBC in routine clinical practice, confirming its effectiveness and safety profile observed in clinical trials.

Background: Due to the complex histological and genomic nature of sarcomas, diagnosing and treating them has proven challenging. Delving into the genomic profiles and molecular markers linked to different sarcoma subtypes will aid in overcoming these obstacles and identifying new potential therapeutic targets. Objectives: The primary objective of this study was to investigate the genomic complexity of sarcoma, while the secondary objective was to identify potential therapeutic targets in the patients with sarcoma from India. Materials and Methods: This retrospective observational study was conducted from January 2020 to February 2024 at 4basecare Precision Health Pvt. Ltd., Bengaluru, India. We carried out comprehensive genomic profiling using gene panels or exome sequencing, including assessment of immunotherapy biomarkers (tumor mutation burden (TMB), microsatellite instability (MSI), programmed death-Ligand 1 (PD-L1)), in a cohort of 263 patients with sarcoma, categorized into 25 sarcoma types, for the present retrospective analysis. Results: We included 263 patients with sarcoma in our study and identified a diverse landscape of pathogenic variants across 138 genes, in 69.5% (183 patients) of the cohort. SNVs were prevalent in TP53 (25.1%; 66 patients), KIT (5.7%; 15 patients), PTEN (4.6%; 12 patients), and RB1 (4.6%; 12 patients), while CDK4 (5.2%; 17 patients) and MDM2 (5.7%; 15 patients) gene amplifications and SS18-SSX2 (1.1%; 3 patients), EWSR1-FLI1 (0.8%; 2 patients), and ASPSCR1-TFE3 (0.8%; 2 patients) gene fusions were recurrent. The majority of the patients harbored mutations affecting cell cycle control (39.2%; 103 patients), PI3K/AKT/MTOR (17.9%; 47 patients), and RAS/RAF/MAPK (14.8%; 39 patients) pathways. The average TMB was 7 mutations/mb, with 13.3% (35 patients) classified as TMB-H. Around 59.3% of the cohort (156 patients) harbored clinically actionable variants of therapeutic significance, including 8.7% of the cohort (23 patients) who were eligible for FDA/NCCN approved therapies. Conclusion: The findings emphasize the clinical usefulness of genomic profiling in guiding precision medicine for sarcoma treatment. Our research offers valuable insights into the genetic makeup of sarcomas, serving as a basis for devising efficient and precise diagnostic approaches and for planning preclinical and clinical studies to develop innovative treatment strategies.

PURPOSEPlatinum-refractory advanced head and neck squamous cell carcinoma (HNSCC) has poor outcomes and limited treatment options, especially in resource-constrained settings. Triple oral metronomic chemotherapy (OMCT), involving low-dose continuous administration of chemotherapeutic agents, has shown promise in phase II studies but lacks evidence from randomized controlled trials. This study evaluated whether triple OMCT improves overall survival (OS) compared with chemotherapy of physician discretion (CPD).PATIENTS AND METHODSIn this phase III randomized open-label study, 214 patients with advanced HNSCC who had previous platinum-based chemotherapy were randomly assigned 1:1 to receive either triple OMCT (arm A) with erlotinib, celecoxib, and methotrexate, or CPD (arm B). The primary end point was OS, with secondary end points including progression-free survival (PFS), quality of life (QOL), and safety. Kaplan-Meier and log-rank tests were used for OS and PFS, and Cox-proportional hazard models estimated hazard ratios. QOL was evaluated using European Organisation for Research and Treatment of Cancer QLQ-C30 and FACT H&N.RESULTSMedian OS was 5 months in arm A and 3.1 months in arm B (hazard ratio [HR], 0.63 [95% CI, 0.47 to 0.83]; P = .00011). Median PFS was 4.8 months in arm A and 2.7 months in arm B (HR, 0.67 [95% CI, 0.52 to 0.87]; P < .0001). Previous treatment was a significant prognostic factor for OS, while age, tumor site, and previous treatment were significant for PFS. Triple OMCT improved global health status, physical functions, fatigue, and insomnia. It was well tolerated, with fewer grade 3 or higher adverse events than CPD (28.0% v 39.3%, P = .03).CONCLUSIONTriple OMCT is an effective and safe treatment for advanced HNSCC after platinum-based chemotherapy.

Hereditary cancer syndromes, driven by pathogenic germline mutations such as those in BRCA1 and BRCA2 and mismatch repair genes, represent a critical but under-addressed frontier in cancer care in low- and middle-income countries (LMICs), including India. Genetic clinics—multidisciplinary platforms offering counselling, testing, and cascade screening—have emerged globally as foundational to precision oncology. However, their implementation in resource-constrained settings remains highly uneven, hindered by infrastructural gaps, socioeconomic barriers, and sociocultural complexities. This narrative review critically synthesises the implementation landscape of genetics clinic for hereditary cancer care, with India as a contextual case. It offers actionable strategies for scaling equitable genetic services in low-resource settings. A targeted literature search was conducted, supplemented by policy documents and global guidelines (ASCO, IARC, WHO). Thirty-one empirical studies were reviewed. Studies were selected based on relevance to cancer genetics service delivery in clinical or public health settings, particularly in low-resource environments. A thematic synthesis approach was used to distil evidence across six domains: clinical value, operational frameworks, barriers to access, ethical and cultural challenges, public engagement, and delivery innovations. Genetics clinic demonstrate significant clinical and preventive impact through risk stratification, targeted therapy, and cascade testing. However, integration into routine care in LMICs is constrained by limited workforce capacity, poor awareness, financial inaccessibility, and weak policy frameworks. Ethical concerns—such as inadequate informed consent and fear of genetic discrimination—compound these barriers. Promising delivery models include tele-genetic counselling, mobile clinics, and decentralised integration into existing oncology services. Effective strategies combine institutional partnerships, legal safeguards, and culturally contextualised communication. Genetics clinic hold transformative potential for hereditary cancer care in resource-limited settings. Achieving equitable implementation requires a locally adapted, ethically grounded, and policy-integrated approach. Investments in training, infrastructure, public education, and governance must align with community needs to enable sustainable genomic integration in LMIC health systems.

Background Immunotherapy has improved outcomes in many advanced solid tumors. In resource-constrained settings, less than 2% of patients can afford standard dose immunotherapy. A recent phase II study showed the efficacy of low-dose immunotherapy in this setting. We used low-dose immunotherapy on a compassionate basis in patients who had progressed on available standard treatment options and standard dose immunotherapy was not feasible. Patients and Methods We retrospectively collected data from the medical oncology department for consecutive patients who had initially received standard lines of therapy followed by low-dose immunotherapy (nivolumab 40 mg) on a compassionate basis. The demographic details, histology, prior treatment, clinical and radiological response, date of disease progression, date of death, and toxicity data were collected. Results A total of 54 consecutive patients, who received low-dose immunotherapy with nivolumab from January 1, 2018 to February 14, 2020, were included in this analysis; 4 patients were not radiologically evaluable. The median age was 50.4 years (range 35–74 years), male:female ratio was 6:1. The most common comorbidities were hypertension and diabetes seen in 12 (22.2%) and 6 (11.1%) patients, respectively. The majority of the patients (70.4%) were of head and neck cancer. The median follow-up was 4.5 months (range 0.5–11.7). Clinical benefit was observed in 18 (33.3%) patients. Partial response and stable disease were achieved in 9 (16.7%) and 5 (9.3%) patients, respectively. Median survival was not reached for these patients. Six months progression-free survival and overall survival were 100 versus 8.7% (hazard ratio [HR] 0.05, 95% confidence interval [CI]: 0.01–0.36; p = 0.003) and 100 versus 29.7% (HR 0.03, 95% CI: 0.00–0.95; p = 0.047), respectively, for responders and nonresponders. The side effects were manageable. Conclusion In resource-constrained settings, low-dose immunotherapy with nivolumab seems to be an effective treatment option. Further studies are warranted to evaluate this approach.

BackgroundALK-positive lung cancers are known to have favorable responses with oral tyrosine kinase inhibitors. Lorlatinib is an approved treatment option post first and second-line ALK inhibitors and is now also in first line. We present a retrospective observational study of the safety and efficacy of patients receiving Lorlatinib in second-line and beyond.MethodsWe conducted a retrospective observational study of ALK-positive patients who received Lorlatinib post-progression or intolerance to initial therapy at the Medical Oncology department. The patients who were started on Lorlatinib between January 2018 to December 2019 were included. The patients underwent routine blood and radiological evaluation every two to three months.ResultsA total of 38 patients received Lorlatinib in the specified period. The median age was 48 years (range 23-68), with 53% of patients being male, 37% having comorbidities; the most common being hypertension and diabetes and 79% of patients were of ECOG-PS1. Twenty-two patients (58%) had received two prior TKIs. The most common sites of metastasis before starting Lorlatinib were brain (55%) and bone (53%). All patients except one received prior whole-brain radiotherapy with 4 receiving radiation twice. The median follow-up period was 49 months (95% CI: 46.4-51.6). Eighty-four percent showed disease control with median progression-free survival (PFS) and overall survival (OS) of 16 months (95% CI 5.4-26.6) and 22 months (95% CI 9.9-34.1) respectively. Twelve patients died without documented progression. Five out of twelve with documented progression had brain involvement while six had lung involvement. Twelve out of twenty-four patients who progressed received subsequent chemotherapy. The most common grade 3 and above toxicities were hypercholesterolemia and hypertriglyceridemia. Three (7.8%) patients required dose reduction.ConclusionThis real-world data confirms the efficacy of Lorlatinib in the second line and beyond with adverse effects matching that of registration studies.

The global demographic and epidemiological transition have led to a rapidly increasing burden of cancer, particularly among older adults. There are scant data on the prevalence and demographic pattern of cancer in older Indian persons. This was a multicentric observational study conducted between January 2019 and December 2020. Data were retrieved from existing electronic databases to gather information on two key variables: the total number of patients registered with oncologists and the number of patients aged 60 years and above. The primary objective was to determine the percentage of older adults among patients with cancer served by these hospitals. Secondary objectives included understanding the prevalence of different types of cancer in the older population, and the sex- and geographic distribution of cancer in older Indian patients. We included 272,488 patients with cancer from 17 institutes across India. Among them, 97,962 individuals (36 %) were aged 60 years and above. The proportion of older adults varied between 20.6 % and 53.6 % across the participating institutes. The median age of the older patients with cancer was 67 (interquartile range, 63-72) years. Of the 54,281 patients for whom the details regarding sex were available, 32,243 (59.4 %) were male. Of the 56,903 older patients, head and neck malignancies were the most prevalent, accounting for 11,158 cases (19.6 %), followed by breast cancer (6260 cases, 11 %), genitourinary cancers (6242 cases, 10.9 %), lung cancers (6082 cases, 10.7 %), hepatopancreaticobiliary (6074, 10.7 %), and hematological malignancies (5226 cases, 9.2 %). Over one-third of Indian patients with cancer are aged 60 years and above, with a male predominance. Head and neck, breast, and genitourinary cancers are the most prevalent in this age group. Characterizing the burden of cancer in older adults is crucial to enable tailored interventions and additional research to improve the care and support for this vulnerable population.

Background: Metastatic breast cancer (MBC) patients have numerous options for treatment. However, it is essential to consider treatments with favorable toxicity profiles and convenient modes of administration. Eribulin has shown effectiveness in aggressive MBC, but there is a lack of sufficient real-world data specific to Indian patients. Patients and methods: We conducted a retrospective audit of patients with MBC who received intravenous Eribulin between 2019 and 2023 at a dosage of 1.4 mg/m2 on days 1 and 8 every 3 weeks. The median Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: During the specified time, 107 consecutive patients with MBC received Eribulin treatment. The median age was 52 years (range, 28-75 years) with 3 patients with male breast cancer. The median number of prior chemotherapy lines and involved sites were 3 (range, 2-5) and 3 (range, 1-6), respectively. Visceral involvement was present in 84 (78.5%) patients. A median of 3 cycles of Eribulin (range, 1-11) was administered. Eribulin resulted in partial responses in 49 (45.8%) patients, stable disease in 11 (10.3%) patients and progressive disease in 47 (43.9%) patients. The median PFS was 4.0 months (95% CI: 3.4-4.6), and the median OS was 10.0 months (95% CI: 8.3-11.7). For patients with triple-negative breast cancer (TNBC), the median OS was 8 months (95% CI: 5.6-10.4), whereas non-TNBC patients had a median OS of 11 months (95% CI: 9.1-12.8) (hazard ratio, 1.9, 95% CI: 1.2-3.1, p = 0.002). Eribulin was well-tolerated, with dose reduction was needed in 9 (8.4%) of the patients in the overall cohort. Conclusion: Eribulin is a viable and safe option for treating heavily pre-treated MBC in real-world settings. The study found comparable efficacy in both TNBC and non-TNBC patients.

BACKGROUND:Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS:In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS:495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION:NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

The communicative interactions of 15 dyads of four- to five-year-olds during pretend play involving routine, or scripted, events were investigated as a function of the children's knowledge of the scripts. Measures of the quantity and quality of interaction and the strategies that the children used to establish mutual knowledge (i.e. assess and adapt to their discourse partner's level of expertise), which is essential to good communication, were examined. Each dyad participated in a MATCHED condition (both members had extensive knowledge of the script) and a MISMATCHED condition (one member had extensive script knowledge and the other did not). Shared script knowledge facilitated communicative interactions, as indicated by more topic maintenance and fewer requests for clarification in the matched condition than in the mismatched condition. The children attempted to establish mutual knowledge more frequently in the mismatched condition than in the matched condition and, moreover, mutual knowledge establishment was related to the children's communicative effectiveness.

Anant RamaswamyIntroduction  The overall survival (OS) of metastatic colorectal cancers (mCRCs) in clinical practice and resource-constrained low- and middle-income countries (LMICS) like India is not known. Materials and Methods  Data of patients with mCRC treated between January 2013 and August 2017 were accessed from a prospectively maintained database. Demographics, disease characteristics, chemotherapeutic regimens, use of monoclonal antibodies, and survival outcomes in treated patients were collected and analyzed. Costs of treatment options as off 2017 were also interpreted. Results  The data of 403 patients satisfied prespecified inclusion criteria and were included for analysis. The median age of the cohort was 48 years (range: 17-86) with a predominance of rectal cancers (63.3%), liver alone metastases (47.1%), and resected primary (69.7%). Signet ring histology was present in 82 patients (20.3%). The most commonly used first-line regimen (CT1) was modified capecitabine-oxaliplatin (53.3%). Two hundred and nineteen patients (54.3%) received second-line systemic therapy (CT2). Patients received a median of two lines of therapy (range: 1-6). MoAbs were used by 48 patients (13.4%) with CT1 and 34 patients (15.5%) with CT2. Median OS of the entire cohort was 17.61 months (95% confidence interval: 15.48-19.74), which was within the predicted range, as per investigator hypothesis. The presence of signet ring histology ( p <0.001), raised carcinoembryonic antigen at baseline ( p =0.017), and the absence of a resected primary ( p <0.001) predicted inferior median OS. Conclusions  Survival of patients with mCRC in a resource-constrained LMIC scenario like India is approximately 12 to 15 months lower than published trial data. Limited access to targeted therapy and newer expensive treatment options due to financial constraints may contribute to this disparity.

Abstract Kumar Prabhash Background  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.

Abstract Akhil Kapoor Purpose  Crizotinib has been one of the standard treatment options for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) based on higher progression-free survival (PFS) and objective response rates in phase III clinical trials. However, real-world data about the long-term efficacy and toxicity of crizotinib is limited. Methods  A retrospective analysis of all patients with ALK-positive NSCLC, treated with crizotinib between March 2014 and December 2016, was performed. The main outcomes measured were PFS, overall survival (OS), and adverse effects. Results  One hundred and eighty-eight patients treated with crizotinib during this period were included in this study. The median age was 50 years (range: 24–74) with a majority being males (73.2%) and 80.3% with a performance status of 0 to 1. The median duration of follow-up was 49.4 months (range: 3.4–86.3%). The median PFS of crizotinib was 17.3 months (95% confidence interval [CI], 13.0–21.6) and 12.8 months (95% CI, 8.1–17.6) when used in first line or subsequent lines, respectively. The median OS was 38.3 months (95% CI, 28.4–48.2). The patients who received crizotinib in the first line had a median OS of 45.5 months (95% CI, 29.6–61.4) as compared with 29.7 months (95% CI, 22.2–37.2) for those who received in subsequent line (hazard ratio, 0.6, 95% CI, 0.4–0.9, p =0.022). The most common all grade toxicities include transaminitis, anemia, fatigue, and corrected QT prolongation. Conclusion  This real-world study confirms the long-term beneficial effects of crizotinib in ALK rearranged NSCLC with favorable toxicity profile like that of the registration studies, in resource constrained settings.