Rajiv Gandhi Cancer Institute and Research Centre

Batra U., Gupta V.G., Raut N., Patil T., Panchal H., Ghadyalpatil N., Pathak A., Desai C., Bondarde S., Jain M., Reyes C.R., Parvatini S., Pai S., Toffalorio F., Thurm H., et. al.

AbstractLorlatinib is approved in India for patients with previously treated anaplastic lymphoma kinase (ALK)–positive advanced or recurrent non-small-cell lung cancer (NSCLC). Owing to the limited number of Indian patients in phase I/II and III studies, a postapproval study was conducted to report the safety and efficacy of lorlatinib in this patient population. In this phase IV study, patients with unresectable advanced and/or recurrent ALK-positive NSCLC resistant or intolerant to ≥1 prior ALK inhibitor were treated with lorlatinib. The primary endpoint was investigator-assessed incidence of treatment-related adverse events (TRAEs). Secondary endpoints were investigator-assessed objective response rate (ORR), intracranial ORR, duration of response (DOR), and intracranial DOR. Among the 100 patients enrolled, the most frequently reported TRAEs were hypertriglyceridemia (57%), hypercholesterolemia (57%), and weight increase (38%). The confirmed ORR and intracranial ORR by the investigator were 41% (95% confidence interval [CI]: 31.9–50.8%) and 36% (95% CI: 24.5–48.8%), respectively. The median systemic and intracranial DORs were not reached. The safety profile of lorlatinib was consistent with that reported in the phase I/II study. Lorlatinib showed a clinically meaningful improvement in ORR and intracranial ORR in patients with unresectable advanced ALK-positive NSCLC. These results support the use of lorlatinib in India for patients with previously treated ALK-positive advanced NSCLC.ClinicalTrials.gov identifier: NCT04541706.

Goyal J., Parihar B., Agarwal N., Manna S., Sharma A., Puri S.K.

AbstractLeiomyosarcoma (LMS) is an uncommon malignant spindle cell neoplasm of smooth muscles, accounting approximately 7% of soft tissue sarcoma. Primary LMS involving bone is an exceptional entity with very few cases described in the literature. The clinical, imaging, and pathological findings were analyzed retrospectively in three confirmed cases of primary LMS of bone. Pain and swelling were the patients' clinical symptoms. On imaging, LMS was often described as a solitary ill-defined lytic lesion with cortical breach depicted on radiograph or computed tomography (CT) scan. Magnetic resonance imaging (MRI) reveals a heterogeneous intermediate-hyperintense signal lesion on T2-weighted imaging (T2WI) with postcontrast enhancement. Histopathology reveals spindle cells arranged in fascicles with nuclear atypia and smooth muscle actin (SMA) positivity on immunohistochemistry (IHC)—consistent with diagnosis of LMS. The patients underwent surgical gross total resection with curative intent, followed by adjuvant chemotherapy or radiotherapy depending upon the stage and histological grade of LMS. On follow-up, the patients were disease free with no evidence of recurrence.

Sreenath N.D., Kushwaha N.K., R. K.M., Govind R.

Abstract Background In India, around 55,000 patients are on dialysis, with a 10–20% annual increase. With the growing dialysis population in India, cancer risk among end-stage renal disease (ESRD) patients is increasing. Managing chemotherapy in these patients is challenging due to limited data and guidelines, leading to treatment uncertainty. Objectives This study provides real-world data from India on the clinical management and outcomes of cancer patients with ESRD undergoing dialysis while receiving chemotherapy. Material and Methods This prospective study analyzed data from five cancer patients with end-stage renal disease (ESRD) on hemodialysis prior to diagnosis of cancer treated at a tertiary oncology center in India. We analyzed the demographic details, cancer staging, treatment regimens, and dosage adjustments. Treatment modifications due to renal dysfunction, toxicities, and patient outcomes were also reviewed over a 12-month follow-up. Results The cohort consisted of 80% (4/5 pts) females, with a median age of 57.8 years. Hypertensive and diabetic nephropathy were the leading causes of ESRD. Cancers included breast (3/5 pts), lung (1/5 pts), and ovarian (1/5 pts), with varying stages of diagnosis. 80% (4/5) of patients required tailored drug management. The Ovarian cancer patient experienced severe hypersensitivity to carboplatin, which was managed conservatively. No grade 3/4 immune-related adverse events occurred, and all patients were alive and disease-free at the one-year follow-up. Conclusion Carefully tailored treatment strategies and a coordinated multidisciplinary approach allowed positive outcomes for cancer patients on dialysis, emphasizing the need for personalized approaches. These findings highlight the importance of refining treatment protocols for this complex group.

Malhotra P., Jain S., Sharma R., Pahuja A., Goyal R., Sharma A., Kapoor G.

Gupta R., Fielder T., Bal M., Chiosea S.I., Dahlstrom J.E., Kakkar A., Kiss K., Laco J., Mittal N., Pasricha S., Samra S., Zidar N., Bullock M., Chernock R., Faquin W., et. al.

Extranodal extension (ENE) increases the risk of recurrence and death in head and neck squamous cell carcinoma (HNSCC) patients and is an indication for treatment escalation. Histopathology forms the mainstay of diagnosing ENE. There is substantial variation in the diagnosis of ENE and related terminology. Harmonising the diagnostic criteria for ENE was identified as a priority by the Head and Neck Consensus Language for Ease of Reproducibility (HN CLEAR) Steering Committee and its global stakeholders. An international working group including 16 head and neck pathologists from eight countries across five continents evaluated whole slide images of haematoxylin and eosin-stained sections depicting potential diagnostic problems through nine virtual meetings to develop consensus guidelines. ENE should be diagnosed only when viable carcinoma extends through the primary lymph node (LN) capsule and directly interacts with the extranodal host environment with or without desmoplastic stromal response. Identifying the original LN capsule and reconstruction of its contour can assist in the detection and assessment of ENE. The term matting is recommended for confluence of two or more nodes due to histologically identifiable tumour extending from one LN to another. Matting constitutes major form of ENE. On the other hand, the terms fusion/adhesion/confluence/conglomeration and other synonyms of adhesion should be limited to confluence due to fibrosis or inflammation without histologically identifiable tumour between involved lymph nodes. Tumour extension along narrow needle tracks or spillage of cyst contents following an FNA do not constitute ENE. The consensus recommendations encompassing the definition of ENE, macroscopic and histologic examination of lymph nodes (LN) and practical guidelines for handling challenging cases are provided.

Doval D.C., Maksud T., Nagarkar R., Thunagappa S.C., Taran R., Prasad S., Manoharan A.T., Jain M., Mehta D., Mohapatra P.N., Gupta S., Singh K.N., Pruthi A., Arora R.

Background Global phase III trials demonstrated efficacy of abemaciclib in patients with HR +/HER2– metastatic breast cancer (BC) as a first-line therapy in combination with a nonsteroidal aromatase inhibitor (MONARCH-3) or with fulvestrant following progression after endocrine therapy (ET) (MONARCH-2). However, there is limited data on safety and tolerability of abemaciclib plus ET in the metastatic BC setting among Indian patients, which the present study aims to address. Materials and Methods An open-label, single-arm, phase IV study was conducted across 16 centers in India to assess the safety and tolerability of abemaciclib in patients with HR +/HER2– locally advanced or metastatic BC. Patients were assigned to either cohort A, ET-naive patients (abemaciclib + anastrozole/letrozole) or cohort B, patients progressing after previous ET (abemaciclib + fulvestrant), targeting the same patient population as the global phase III MONARCH-3 and MONARCH-2 trials, respectively. Primary endpoints were all-cause adverse events (AEs) including serious AEs (SAEs). Statistical Analysis The statistical analysis was conducted using SAS Version 9.4. Results Two hundred patients were enrolled, with a mean age of 54 years, most (77.0%) were aged ≤ 65 years. The median duration of exposure was similar in both cohorts (cohort A vs. B: 24.3 vs. 24.4 weeks). Overall, 75.5 % of patients reported all-cause AEs, of which 38.5% of the patients reported AEs Common Terminology Criteria for Adverse Events grade 3 and above. The most common grade 3 and above all-cause AEs for abemaciclib were neutropenia (19.0%), followed by anemia (14.0%) and diarrhea (5.5%). Fourteen (7.0%) patients encountered SAEs, including infections (2.0%) and gastrointestinal disorders (1.5%). Most of the patients continued their treatments with appropriate dose reductions (25.5%) and dose omissions (40.5%), and only 2.5% of patients discontinued study treatment due to treatment-related AEs. Conclusion Abemaciclib in combination with ET was found to have an acceptable tolerability in Indian patients with HR +/HER2– advanced and metastatic BC, consistent with the established safety data as reported in the pivotal global studies. No new clinical safety concerns were identified, with most of the reported AEs and SAEs managed by dose adjustments.

Joga S., Goyal S., Mehta A., Sharma M., Koyyala V.P., Goyal P., Aggarwal C., Swamy M.S., Patel A.B., Nathany S., Suryavanshi M., Sharma A., Saraswat S.N., Soni S., Jain A., et. al.

Background Colorectal cancer (CRC) is a heterogeneous disease morphologically, histologically, and molecularly. Most of the studies are on this molecular heterogeneity and their clinicopathological correlation from the western world. Very few studies have been done in India. Objectives The aims of this study were to evaluate the clinical and pathological profile of CRCs, to determine the frequency of molecular subtypes of CRCs, to correlate between the molecular subtypes and their clinicopathological features, and to determine the association between different molecular subtypes of CRC. Materials and Methods A prospective noninvasive interventional study was done on 50 patients (both outpatients and inpatients) with newly diagnosed CRCs presenting to the Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi, from February 2019 to March 2020. Clinical and histopathological data were collected from case sheets as per the study proforma: history and physical examination, noninvasive and invasive imaging, and histopathological reports. Patients in whom tissue was insufficient or not available for testing for at least three of five molecular markers (KRAS, NRAS, BRAF, MSI, and MLH1 methylation) were excluded. The results were analyzed with SSPS 23.0 software. For comparison of the frequencies among groups, the chi-squared test and the Fisher exact test were used. A p-value of less than 0.05 was considered statistically significant. Results The median age was 53 years. The majority of the males (54%) had CRC and 44% were right-sided colon tumors. Of the 50 patients with CRC, 40, 0, 4, and 4% had KRAS mutation, NRAS and BRAF mutation, and deficient mismatch repair (dMMR), respectively. KRAS mutation was significantly associated with upfront liver metastases (p = 0.02) and well/moderate differentiation (p = 0.02). BRAF wild-type tumors were likely to be well differentiated (p = 0.02), and moreover, half of them (52%) had MLH1 promoter methylation. The proportion of dMMR was higher in male patients (p = 0.04). Deficient mismatch repair was associated with well/moderate differentiation (p = 0.02), early stage (p =0.02), and mild peritumoral lymphocytes (p = 0.01). None of the dMMR patients had stage IV CRC. In all, 27% of the patients (3/11) with dMMR tumors had germline mutation of the dMMR genes. The majority of dMMR tumors (43%, 3 out of 7) had MLH1 promoter methylation. Overall, 45% (5/11) of dMMR tumors harbored KRAS mutation. Conclusion In conclusion, this is a prospective study evaluating the correlations between RAS/BRAF mutation and dMMR status with clinicopathological characteristics in Indian CRC patients, which is slightly similar to worldwide reports with some exceptions. To the best of our knowledge, this is the first study to evaluate the molecular marker combinations in CRC in India.

Bansal N., Sachdeva I., Bhurani D., Agarwal N.

Abstract Background Multi-drug resistance in gram-negative bacilli is major cause of concern in managing patients with febrile neutropenia particularly among hematology-oncology patients. Reversing AMR has never been demonstrated previously in this setting. Table of various parameters comparing Cohort A and B Methods This retrospective study compares clinical and microbiological outcomes of patients admitted to hematology-oncology unit of a tertiary care center in India with febrile neutropenia and gram-negative bacteremia. Patients admitted from April 2019- April 2020 were included in Cohort A and April 2023-April 2024 were included in Cohort B. Bar diagram showing change in resistance pattern in two cohorts Results A total of 212 patients (Cohort A: 114, Cohort B 98) were included in this study (Table 1). Mean age (53 ± 21.2 years vs 46.5 ± 17.5; p = 0.417) and gender distribution (females: 40.3% vs 36.7%; p = 0.58) were comparable and so was distribution of malignancies. Mean Sequential Organ Failure Assessment Score (6 ± 2.29 vs 5 ±3.50; p = 0.245), mean Charlson co-morbidity Index (3 ± 2.4 vs 3 ± 2.1; p = 0.65), mean Pitts Bacteremia score (1 ± 1.46 vs 1 ± 1.58; p = 0.334) and 30 day crude mortality (28.7% vs 28.6%; p = 0.935) were not statistically significant between the two cohorts. Incidence (Figure 1)of carbapenem resistance (CR) Klebsiella pneumoniae (56 (90.3%) vs 16 (47.1%); p < 0.01), CR E. coli (14 (43.7%) vs 6 (23.1%); p = 0.099) and DTR (difficult-to-treat) Pseudomonas aeruginosa (10 (83.3%) vs 2 (10.0%); p < 0.01) significantly reduced in Cohort B as compared to Cohort A. Involvement of Infectious Disease (ID) service, following antibiotic stewardship (AMS) team advice, improved diagnostic facility and infection control were major interventions during the study period. Conclusion This study highlights that incorporating ID service and following AMS activities along with other infrastructure development can reverse AMR in high risk setting like febrile neutropenia among hematology-oncology patients. Disclosures All Authors: No reported disclosures

Rai S., Pasricha S., Tandon S., Singh A., Bharadwaj R., Gupta M., Agarwal M.

Oral cavity verrucous growth can be benign, malignant, or have the potential for malignant transformation. The present study aims to explore the hypothesis that all preoperatively diagnosed oral cavity verrucous hyperplasia (OCVH) carry a risk of malignancy in subsequent resection specimens and to re-analyse the risk factors that would indicate malignancy in these patients. This is a retrospective analysis of consecutively diagnosed 30 patients with OCVH on diagnostic biopsy who presented at our institute between February 2018 and January 2021. Among these, patients with malignancy in their final histopathological examination (HPE) were re-analysed for potential clinicopathological risk factors that could anticipate malignancy preoperatively. On subsequent resection, 53.4% (16) of patients had invasive malignancy, 10% (3) of patients had high-grade dysplasia, and 3.3% (1) of patients had mild dysplasia on the final HPE. Thus, only 30% (9) of patients had retained the pre-operative diagnosis of verrucous hyperplasia without dysplasia (3.3% (1) patient was given radical radiotherapy and was excluded from analysis). In addition, age ≥ 50 years (p value = 0.006), repeat biopsies (p value = 0.009), and bone erosion on imaging (p value < 0.001) were clinical-radiological risk factors significantly associated with the risk of malignancy at diagnosis in linear regression analysis. The risk of malignancy can be stratified with proper patient evaluation after a thorough history and clinical-radiological assessment in patients with OCVH on diagnostic biopsy. Thus, these lesions should undergo formal oncologic resection if clinical-radiological suspicion is high, even if preoperative biopsy is negative.

Bansal N., Sukhwani K.S., Ganta V.

Rathnasamy N., Lavingia V., Aggarwal S., Talwar V., Shukla P., Rohtagi N., Prathasarathy K.M., Gupta D., Pasricha R., Pasricha S., Choudhary R.K., Goyal G., Rawat S., Parikh P., Selvasekar C.

Evidence is mounting that circulating tumor deoxyribonucleic acid can be tested accurately, frequently, and in a noninvasive form. Its role in monitoring patients with cancer, particularly colorectal cancer, is increasing. In this brief review, we discuss its current role when measured using next-generation sequencing-based methods.

Lahiri A., Yadav V., Arora V., Sharma P., Dewan A.K.

Intraoperative parathyroid gland (PG) localization remains challenging during thyroid surgeries, contributing to postoperative hypocalcemia and hypoparathyroidism. This study assessed the efficacy of indocyanine green (ICG) fluorescence in identifying and preserving PGs during thyroid surgeries and its correlation with postoperative outcomes. This ambispective observational study included 57 patients undergoing thyroid surgeries using ICG and compared outcomes with 56 historical controls. ICG was administered intravenously in two 5 mg boluses. Parathyroid identification rates, fluorescence intensity, and postoperative calcium and parathormone levels were assessed. Fluorescence intensity was qualitatively scored on a 1–3 scale. ICG significantly improved PG identification (92.5% vs 69.3% with white light alone). Postoperative hypocalcemia occurred in 22.81% of ICG patients compared to 39.29% in controls (p = 0.045). Hypoparathyroidism rates were 10.53% and 32.14% respectively (p = 0.005). Higher fluorescence intensity (FI) correlated with lower risk of postoperative hypocalcemia (p = 0.026) and combined hypocalcemia and hypoparathyroidism (p = 0.046). Considering both FI 2 and 3 as positive yielded 100% sensitivity and 85.7% accuracy. When only FI 3 was considered positive, sensitivity was 78.4%, specificity was 50%, and accuracy was 69.4%. ICG fluorescence is a safe and effective tool for enhancing PG identification and preservation in thyroid surgeries, significantly reducing postoperative hypocalcemia and hypoparathyroidism. It also helps in confirming the vascularity of the PGs post thyroidectomy. Fluorescence intensity of preserved PGs, rather than quantity, better predicts postoperative outcomes. These findings support the integration of ICG fluorescence imaging and the application of our methodology in thyroid surgeries to improve postoperative results.

Batra U., Prabhash K., Noronha V., Deshpande R., Khurana S., Bhat G.M., Mistry R., Agarwala V., Rajpurohit S., Poladia B., Sharma M., Banday S.Z.

PURPOSE The spectrum of EGFR is inadequately researched in patients with early-stage non–small cell lung cancer (NSCLC) in India. EARLY-epidermal growth factor receptor (EGFR) India (ClinicalTrials.gov identifier: NCT04742192 ), as part of a noninterventional, real-world global study, evaluated the prevalence of EGFR mutations in early-stage NSCLC in India. METHODS Prospective data from adult patients with surgically resected stage IA to IIIB (American Joint Committee on Cancer eighth edition) NSCLC between March 2021 and October 2022 were analyzed. In addition to descriptive statistics, Fisher's exact test with Monte Carlo was used to determine the association between EGFR mutations and clinicodemographic parameters. RESULTS Of 74 patients (median age, 57.0 [range, 33.0-77.0] years) enrolled from eight centers in India, 73.0% (54 of 74) were males, 56.1% (37 of 66) were nonsmokers, and 95.9% (71 of 74) had adenocarcinoma. The EGFR mutation prevalence was 26.0% (19 of 73), of which Exon-19 deletions were the predominant subtype (13, 68.4%) followed by Exon 21-L858R (4, 21.1%), Exon 20-T790M (1, 5.3%), and compound (1, 5.3%) mutations. Nearly half (48.6%, 36 of 74) of the patients underwent only surgical resection. The remaining 51.4% (38 of 74) of the patients were prescribed neoadjuvant (n = 12; 16.2%) and adjuvant (n = 31; 41.9%) systemic therapies, and one patient (1.4%) received radiotherapy along with systemic therapy. In 60 patients with stage IB to IIIB NSCLC, systemic therapies, mainly platinum-based chemotherapy, were prescribed in 36 (60.0%). Only 8.1% (6 of 74) of the patients were prescribed EGFR-tyrosine kinase inhibitor (TKI), of which two received neoadjuvant and four were planned for adjuvant EGFR-TKI. Two (2.7%) patients were prescribed adjuvant immunotherapy. The univariate analysis showed higher odds of EGFR mutation for females (odds ratio, 3.96; P = .017). CONCLUSION EARLY-EGFR India results showed the prevalence of EGFR mutation to be 26%. The study emphasized the pressing need for up-front biomarker testing at diagnosis to ensure optimal and timely personalized treatment.

Batra U., Nathany S.

Non-small-cell lung cancer (NSCLC) is the poster child of personalized medicine. With increased knowledge about biomarkers and the consequent improvement in survival rates, NSCLC has changed from being a therapeutic nihilistic disease to that characterized by therapeutic enthusiasm. The routine biomarkers tested in NSCLC are EGFR, ALK, and ROS1. However, several additional biomarkers have been added to the diagnostic landscape. Current guidelines recommend testing at least seven biomarkers upfront at the time of NSCLC diagnosis—emphasizing the wide range of targets and corresponding therapies that can be leveraged for disease management. Sequential single-gene testing is not only time-consuming but also leads to tissue exhaustion. Multigene panel testing using next-generation sequencing (NGS) offers an attractive diagnostic substitute that aligns with the evolving dynamics of precision medicine. NGS enables the identification of point mutations, insertions, deletions, copy number alterations, fusion genes, and microsatellite instability information needed to guide the potential use of targeted therapy. This article reviews the existing guidelines, proposed recommendations for NGS in non-squamous NSCLC, real-world data on its use, and the advantages of adopting broader panel-based NGS testing over single-gene testing.

Lohani S., Prasai G., Tandon S., Ahlawat P., Antony V., Bellige A.R., Patodi V., Mahajan S., Umesh P., Nayak A., Gairola M.

Advanced Oral Cavity Squamous Cell Carcinoma (OSCC) poses challenges for upfront resection. While surgery followed by adjuvant treatment is standard, induction chemotherapy is explored for better resectability and organ preservation. Its efficacy in unresectable cases is still uncertain and yet to be proven. A retrospective study was done at our institute by reviewing the institutional database from January 2018 to December 2020, where patients with biopsy proven OSCC who were considered unresectable disease but treated with curative intention recruited. All the patients recruited were divided into two cohorts: Radical CCRT (Arm A) or Induction Chemotherapy (IC) followed by Chemo Radiotherapy (CCRT) (Arm B) were evaluated. The patients were analyzed for progression free survival (PFS) and Overall Survival (OS). One hundred and eighty (180) patients of locally advanced unresectable OSCC were treated with curative intent. However, data of 22 (12%) patients were excluded because of incomplete data in the database. Of remaining 158 patients, 120 (76%) and 38 (24%) were divided into arm A and B, respectively. Baseline characteristics were statistically similar in both arms except for sub site distribution with higher percentage of buccal mucosa primary [25.8% vs 42.1% in arm A vs. B respectively, p-value 0.047]. With a median follow-up of 16 (range 2–73) months, the Progression Free Survival (PFS) observed was 11 vs. 12 months [p-value 0.460] and Overall Survival (OS) was 16 vs. 17 months [p-value 0.450] in arms A and B respectively. Our study showed IC doesn’t have benefit in terms of PFS or OS compared to upfront CCRT in unresectable OSCC treated in a definitive setting. However, a more robust data and literature is required to come up with a clear answer for this clinical question.