Search

Byline: S. Moorthy, H. Elhateer, SKD. Majumdar, S. Mohammed, R. Patnaik, Narayanamurty. Aim of Study: Breast conserving surgery (BCS) is the standard treatment for stage I and II breast cancer. [...]

Background: Hand-foot syndrome (HFS) is one of the most common toxicities experienced by patients receiving systemic chemotherapy agents such as capecitabine and multikinase inhibitors such as sorafenib. Several randomised controlled trials (RCTs) have investigated the efficacy and safety of prophylactic agents such as pyridoxine, celecoxib, urea cream and cystine/theanine in managing HFS. This network meta-analysis (NMA) evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS., Objective: To examine the comparative efficacy and safety of interventions for preventing systemic chemotherapy-induced HFS in patients with cancer., Methods: We searched PubMed, Embase and clinical trial registry for RCTs of interventions for preventing HFS. Bayesian NMA was performed to estimate the OR with 95% credible intervals (CrI) from both direct and indirect evidence. The outcome measures were the incidence of HFS (grade ≥1) and moderate to severe HFS (grade ≥2). Adverse drug reactions were discussed descriptively., Results: A total of 15 RCTs with 2715 patients with 12 prophylactic strategies were included. The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68). But none of the preventive interventions could prevent the incidence of HFS (grade ≥1)., Conclusion: Only celecoxib (200 mg two times per day) showed significant prevention of the incidence of moderate to severe HFS. Pyridoxine (400 mg once daily) and urea cream (10%) have to be evaluated further in larger randomised trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors have no conflicts of interest to disclose.

CMTM6, a type 3 transmembrane protein, is known to stabilize the expression of programmed cell death ligand 1 (PD-L1) and hence facilitates the immune evasion of tumor cells. Recently, we demonstrated that CMTM6 is a major driver of cisplatin resistance in oral squamous cell carcinomas (OSCC). However, the detailed mechanism of how CMTM6 rewires cisplatin resistance in OSCC is yet to be explored. RNA sequencing analysis of cisplatin-resistant OSCC lines stably expressing Nt shRNA and CMTM6 shRNA revealed that CMTM6 might be a potential regulator of the ribosome biogenesis network. Knocking down CMTM6 significantly inhibited transcription of 47S precursor rRNA and hindered the nucleolar structure, indicating reduced ribosome biogenesis. When CMTM6 was ectopically over-expressed in CMTM6KD cells, almost all ribosomal machinery components were rescued. Mechanistically, CMTM6 induced the expression of C-Myc, which promotes RNA polymerase I mediated rDNA transcription. In addition to this, CMTM6 was also found to regulate the AKT-mTORC1-dependent ribosome biogenesis and protein synthesis in cisplatin-resistant lines. The nude mice and zebrafish xenograft experiments indicate that blocking ribosome synthesis either by genetic inhibitor (CMTM6KD) or pharmacological inhibitor (CX-5461) significantly restores cisplatin-mediated cell death in chemoresistant OSCC. Overall, our study suggests that CMTM6 is a major regulator of the ribosome biogenesis network and targeting the ribosome biogenesis network is a viable target to overcome chemoresistance in OSCC. The novel combination of CX-5461 and cisplatin deserves further clinical investigation in advanced OSCC., (© 2022 Federation of American Societies for Experimental Biology.)

Introduction: Despite the development of targeted therapies for the management of oral cancer patients, the cost of treatment is a concern in middle- and low-income countries. The present study assessed the feasibility of low-cost metronomic therapy as an alternative treatment modality in patients with unresectable or inoperable oral cancers., Methodology: The study was a prospective, single-arm study. Unresectable, inoperable, and metastatic lip and oral cavity cancers were started on metronomic therapy, a combination of oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily, as palliative therapy. The primary endpoint was overall survival. The secondary endpoints were a response to metronomic therapy, compliance, and toxicity., Results: From June 2018 to May 2020, 25 patients were started on metronomic therapy. The median age was 60 years. The median overall survival was 8.8 months. At eight weeks of therapy, 11 patients (44%) had a partial response, ten patients had stable disease (40%), and four patients had progressive disease (16%). The compliance with the therapy was 100%, and one patient (4%) developed grade III toxicity., Conclusions: Considering the resource constraints and cost limitations in low and middle-income countries, oral metronomic therapy in the form of methotrexate and celecoxib should be regarded as a suitable regimen in the palliative treatment of patients with unresectable, metastatic, or advanced, recurrent cancers.

Purpose: To investigate and evaluate the feasibility of a simple modified Divided Planning Target Volume (DPTV) optimization method in radiation therapy planning of lung cancer patients., Methods: A cohort of 15 patients of Non-Small Cell Lung Cancer (13 patients stage III and two patients of stage II) who were previously treated with Concurrent Chemo Radiation Therapy were included in the study. The planning modality was Volumetric Modulated Arc Therapy, and the dose prescription was 60 Gray in 30 fractions. In this study, we attempted to replan by dividing the previous Single Planning Target Volume (SPTV) into a DPTV. All the treatment plans were revised and again optimized for DPTV with required dose constraints as in SPTV. The dosimetric parameters that were achieved for target and normal structures were recorded in both the optimization methods., Results: Dosimetric target coverage (D95%) (p-value = 0.0001), dose homogeneity (p-value =0.0001) and conformity (p-value = 0.044) were improved by the DPTV optimization. The volume of the oesophagus receiving 35 Gy was found to be higher in the DPTV arm (p-value = 0.02) compared to the SPTV arm, but the volume of the oesophagus receiving 50 Gy was found to be similar (p-value = 0.122)., Conclusion: In radiation therapy planning of lung cancer, the DPTV optimization method has better dose coverage to the target volume, homogeneity, as well as conformity than the stsndsrd SPTV method. Therefore, the DPTV optimization method can be a simple and efficient alternative to the SPTV method in lung cancer., (Copyright © 2022. Published by Elsevier Inc.)

Managing of radiotherapy department in many cancer centers in India has become very challenging during the COVID-19 pandemic. A radiotherapy center has to deal with multiple problems such as long treatment duration of each patient, high caseload on each radiotherapy machine, a limited number of qualified technical staff available, and equipment maintenance. For the department's smooth running, both the patient and healthcare worker must be safe from contacting COVID-19. A robust and planned strategy is required for prevention, screening, and awareness among all. To access our preparedness and evolve by gaining from other radiotherapy centers, a study was conducted using questionnaires and responses collected from different cancer centers in India., Competing Interests: None

Background: Chemoresistance is one of the major factors for treatment failure in OSCC. Identifying key resistance triggering molecules will be useful strategy for developing novel treatment methods., Methods: To identify the causative factors of chemoresistance, we performed RNA sequencing and global proteomic profiling of human OSCC lines presenting with sensitive, early and late cisplatin-resistance patterns., Results: From the common set of dysregulated genes from both the analysis, RRBP1 was identified to be upregulated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analysis of OSCC patient sample indicates that RRBP1 expression is upregulated in chemotherapy-non-responder tumours as compared to chemotherapy-responder tumours. Genetic (knockout) or pharmacological (Radezolid, represses expression of RRBP1) inhibition of RRBP1 restores cisplatin-mediated cell death in chemo-resistant OSCC. Mechanistically, RRBP1 regulates Yes-associated protein1 (YAP1), a key protein in the Hippo pathway to induce chemoresistance. The PDC xenograft data suggests that knockout of RRBP1 induces cisplatin-mediated cell death and facilitates a significant reduction of tumour burden., Conclusion: Overall, our data suggests that (I) RRBP1 is a major driver of cisplatin-resistance in OSCC, (II) RRBP1 regulates YAP1 expression to mediate cisplatin-resistance, (III) Radezolid represses RRBP1 expression and (IV) targeting RRBP1 reverses cisplatin-induced chemoresistance in advanced OSCC.

Patients with cancer are at a higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) than the general population. In India, it has become a significant health problem of utmost importance, and India's Government has issued health advisories. Lockdown brought many unforeseen problems for patients and hospitals, leading to confusion and chaos. The aim of this article is to identify various issues related to our hospital, follow-up, nutrition, treatment and psychosocial issues. Multiple changes were made in the hospital, departmental and treatment policy for cancer patients' convenience and safety. As India is in the peak of COVID-19, these types of modifications and modifications of treatment schedules will be the 'New Normal'., Competing Interests: The authors have no conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

The current retrospective multicenter study evaluated the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS; DoceAqualip) based chemotherapy in patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The medical charts of patients with gastric and GEJ adenocarcinoma, who were treated with NDLS (50-75 mg/m 2 ; 3 weekly cycles) based chemotherapy and followed-up from April 2014 to September 2018, were analyzed. The study endpoints included overall response rate (ORR) and disease control rate (DCR) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were also evaluated. Of the 43 patients with gastric (n=39) and GEJ (n=4) adenocarcinoma, efficacy evaluation was available in 35 (neoadjuvant, 17/18 patients; metastatic, 18/25 patients). In the neoadjuvant setting, an ORR of 58.82% and a DCR of 94.11% were observed, whereas in the metastatic setting, the ORR was 77.77% and the DCR was 83.33%. In the neoadjuvant setting, at a follow-up ranging from 0.7 to 41.2 months, the median OS was not reached. In the metastatic setting, the median OS was 31.9 months at a follow-up ranging from 0.2 to 50.3 months. At least one adverse event (AE) was reported in 24 patients. Anemia, lymphopenia and thrombocytopenia were the most common hematological AEs, while nausea, vomiting and weakness were the most common non-hematological AEs. NDLS based treatment was well-tolerated without any new safety concerns. Overall, NDLS-based chemotherapy was effective and well-tolerated in the management of gastric and GEJ adenocarcinoma., (Copyright © 2020, Spandidos Publications.)

Background: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma., Methods: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1)., Results: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy., Conclusion: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR., Competing Interests: None