Browsing by Author "Manjusha Pal"

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Efficacy and safety of cetuximab-based versus platinum-based chemoradiation in HNSCC: evidence from a meta-analysis of 10 randomized controlled trials
(Springer Science and Business Media Deutschland GmbH, 2025) Tarun Kumar; Nishu Kesh; Atindra Kumar Pandey; Ankita Chakrawal; Bhavana Singh; Manjusha Pal; Monika Rajput; Ruhi Dixit; Esha Pai; Manoj Pandey
Background: Platinum-based chemoradiotherapy (CTRT) is the standard treatment for head and neck squamous cell carcinoma (HNSCC). While cetuximab-based radiotherapy (CxRT) has been proposed as an alternative, its efficacy remains controversial. Multiple meta-analyses have compared CxRT with CTRT for HNSCC though they combined randomized controlled trials (RCTs) with lower-evidence studies, compromising result validity. This study presents the first meta-analysis using exclusively RCT data, providing the highest level of evidence for clinical decision-making. Methods: We systematically searched MEDLINE, Embase, Cochrane, and SCOPUS, identifying 10 RCTs (n = 2,557 patients). Primary outcomes included overall survival (OS), disease-free survival (DFS), and all-cause mortality; secondary outcomes were Grade ≥ 3 toxicities. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random effect models. Results: CxRT was associated with a 50% higher recurrence risk (HR 1.50, 95% CI 1.07–2.10) and 27% increased all-cause mortality (OR 1.27, 95% CI 1.05–1.55) compared to CTRT. OS did not differ significantly (HR 1.33, 95% CI 0.79–2.22). Toxicity profiles varied: CxRT had higher mucositis (OR 1.17, 95% CI 1.04–1.32) and skin rash (OR 3.46, 95% CI 1.28–9.36), while CTRT showed more anemia (OR 0.15, 95% CI 0.05–0.52) and nausea/vomiting (OR 0.31, 95% CI 0.19–0.53). Conclusion: CxRT is inferior to CTRT in HNSCC, with poorer disease control and survival outcomes. The lack of biomarker (EGFR/RAS) stratification in trials may have contributed to suboptimal patient selection. While CxRT may be an option for cisplatin-ineligible patients, platinum-based therapy appears to be the standard. Future research should optimize cetuximab’s role through biomarker-driven selection. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2025.
Novel mutations in a second primary gastric cancer in a patient treated for primary colon cancer
(BioMed Central Ltd, 2023) Roli Purwar; Madhumita Tripathi; Monika Rajput; Manjusha Pal; Manoj Pandey
A 60-year-old man presented with complaints of abdominal pain and melena. Patient had a history of colon cancer 16 years back and had undergone right hemi colectomy for microsatellite instability (MSI) negative, mismatch repair (MMR) stable, T2N0 disease with no mutations on next-generation sequencing (NGS). Investigations revealed a second primary in stomach (intestinal type of adenocarcinoma) with no recurrent lesions in colon or distant metastasis. He was started on CapOx with Bevacizumab and developed gastric outlet obstruction. Total gastrectomy with D2 lymphadenectomy and Roux-en-Y oesophageao-jejunal pouch anastomosis was done. The histopathology showed intestinal type of adenocarcinoma with pT3N2 disease. NGS showed 3 novel mutations in KMT2A, LTK, and MST1R gene. The pathway enrichment analysis and Gene Ontology were carried out, followed by the construction of protein–protein interaction network to discover associations among the genes. The results suggested that these mutations have not been reported in gastric cancer earlier and despite not having a direct pathway of carcinogenesis they probably act through modulation of host of miRNA’s. Further studies are needed to investigate the role of KMT2A, LTK, and MST1R gene in gastric carcinogenesis. © 2023, The Author(s).
Role of PARP inhibitors beyond BRCA mutation and platinum sensitivity in epithelial ovarian cancer: a meta-analysis of hazard ratios from randomized clinical trials
(BioMed Central Ltd, 2023) Roli Purwar; Rakesh Ranjan; Manjusha Pal; Satyanshu K. Upadhyay; Tarun Kumar; Manoj Pandey
Background: PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear. Methods: A meta-analysis of hazard ratios (HR) of randomized control trials (RCTs) was conducted to study the role of PARPi. The published RCTs comparing the efficacy of PARP inhibitors alone or in combination with chemotherapy and/or target therapies versus placebo/chemotherapy alone/target therapy alone in primary or recurrent ovarian cancer settings were selected. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: A total of 14 primary studies and 5 updated studies are considered, consisting of 5363 patients. Overall, HR for PFS was 0.50 [95% CI 0.40–0.62]. HR of PFS was 0.94 [95% CI 0.76–1.15] in the PROC group, 0.41 [95% CI 0.29–0.60] was in HRD with BRCA unknown (BRCAuk), 0.38 [95% CI 0.26–0.57] in HRD with BRCAm, and 0.52 [95% CI 0.38–0.71] in HRD with BRCAwt. In the HRP group, overall HR for PFS was 0.67 [95% CI 0.56–0.80], 0.61 [95% CI 0.38–0.99] in HRD unknown with BRCA wt, and 0.40 [95% CI 0.29–0.55] in BRCAm HR for PFS. Overall, HR for OS was 0.86 [95% CI 0.73–1.031]. Conclusions: The results suggest that PARPi have a meaningful clinical benefit in PSOC, HRD, BRACm, and also in HRP and PROC; however, the evidence is not sufficient to recommend their routine use and further studies are needed to expand their role in the HRP and PROC groups. © 2023, The Author(s).
Understanding genetic variations associated with familial breast cancer
(BioMed Central Ltd, 2024) Manjusha Pal; Doutrina Das; Manoj Pandey
Background: Breast cancer is the most frequent cancer among women. Genetics are the main risk factor for breast cancer. Statistics show that 15–25% of breast cancers are inherited among those with cancer-prone relatives. BRCA1, BRCA2, TP53, CDH1, PTEN, and STK11 are the most frequent genes for familial breast cancer, which occurs 80% of the time. In rare situations, moderate-penetrance gene mutations such CHEK2, BRIP1, ATM, and PALB2 contribute 2–3%. Methods: A search of the PubMed database was carried out spanning from 2005 to July 2024, yielding a total of 768 articles that delve into the realm of familial breast cancer, concerning genes and genetic syndromes. After exclusion 150 articles were included in the final review. Results: We report on a set of 20 familial breast cancer -associated genes into high, moderate, and low penetrance levels. Additionally, 10 genetic disorders were found to be linked with familial breast cancer. Conclusion: Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered. © The Author(s) 2024.