Pleural effusion supernatant: a reliable resource for cell-free DNA in molecular testing of lung cancer.

INTRODUCTION: DNA extracted from malignant pleural effusion (PE) sediments is the traditional source of tumor DNA for predictive biomarker molecular testing (MT). Few recent studies have proposed the utility of cell-free DNA (cfDNA) extracted from effusion cytology centrifuged supernatants (CCS) in MT. The aim of this study was to assess the feasibility and utility of molecular testing on cfDNA extracted from PE CCS in lung cancer patients. METHOD: The study was of prospective design. All PE CCS were collected and stored. Subsequently, in patients confirmed as primary lung adenocarcinoma (LUAD) and where patient matched effusion sediment/tissue biopsy/plasma was being tested for EGFR mutations, cfDNA extraction and EGFR MT by real-time polymerase chain reaction (qPCR) were performed. Custom panel targeted next-generation sequencing (NGS) (Ion Torrent; Thermo Fisher, Carlsbad, CA) was also performed wherever feasible. RESULTS: Out of 299 PE CCS collected, 20 CCS samples were included in the study. Concordant EGFR mutations were detected in pleural effusion CCS of 10 of 11 (91%) EGFR mutant cases as per qPCR performed on the matched sediment DNA (n = 8), lung biopsy (n = 2), and plasma (n = 1) samples. In 1 positive sample, CCS detected additional EGFR T790M mutation. Among 10 CCS samples also tested by NGS, additional EGFR mutations missed by qPCR were picked up in 2 (2 of 10). Success of mutation detection in CCS cfDNA did not correlate with cfDNA quantity or tumor fraction in sediment. CONCLUSIONS: cfDNA from effusion CCS is a reliable and independent source of tumor DNA highly amenable for MT and complement results from other tumor DNA sources for comprehensive mutation profiling in LUAD patients.

Retrospective application of WHO reporting system for lung cytopathology with assessment of risk of malignancy.

INTRODUCTION: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category. MATERIALS AND METHODS: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually. RESULTS: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%. CONCLUSIONS: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

SMART-ESAS: Smartphone Monitoring and Assessment in Real Time of Edmonton Symptom Assessment System Scores for Patients With Cancer.

PURPOSE: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting. METHODS: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden. RESULTS: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001). CONCLUSION: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

Concordance of Immunohistochemistry and Fluorescence In Situ Hybridization in the Detection of Anaplastic Lymphoma Kinase (ALK) and Ros Proto-oncogene 1 (ROS1) Gene Rearrangements in Non-Small Cell Lung Carcinoma: A 4.5-Year Experience Highlighting Challenges and Pitfalls.

CONTEXT.­: ALK and ROS1 rearrangements are essential biomarkers to be tested in advanced lung adenocarcinomas. While D5F3 Ventana assay is a companion diagnostic for anaplastic lymphoma kinase-targeted therapy, immunohistochemistry is only a screening tool for detecting ROS1 rearrangement. Confirmation by cytogenetic or molecular techniques is necessary. OBJECTIVE.­: To evaluate the utility of ALK and ROS1 fluorescence in situ hybridization as a complement to immunohistochemistry in routine predictive biomarker testing algorithms. DESIGN.­: The study was ambispective, spanning 4.5 years during which lung adenocarcinoma samples were subjected to EGFR mutation testing by real-time polymerase chain reaction, and ALK/ROS1 rearrangement testing by immunohistochemistry (Ventana D5F3 assay for anaplastic lymphoma kinase protein; manual assay with D4D6 clone for Ros proto-oncogene 1 protein). Fluorescence in situ hybridization was performed in all anaplastic lymphoma kinase equivocal and Ros proto-oncogene 1 immunopositive cases. RESULTS.­: Of 1874 samples included, EGFR mutations were detected in 27% (481 of 1796). Anaplastic lymphoma kinase immunohistochemistry was positive in 10% (174 of 1719) and equivocal in 3% (58 of 1719) of samples tested. ALK fluorescence in situ hybridization showed 81% (77 of 95) concordance with immunohistochemistry. Ros proto-oncogene 1 immunopositivity was noted in 13% (190 of 1425) of cases, with hybridization-confirmed rearrangements in 19.3% (26 of 135) of samples, all of which showed diffuse, strong- to moderate-intensity, cytoplasmic staining in tumor cells. Ros proto-oncogene 1 protein overexpression without rearrangement was significantly common in EGFR-mutant and ALK-rearranged adenocarcinomas. CONCLUSIONS.­: Immunostaining is a robust method for ALK-rearrangement testing, with fluorescence in situ hybridization adding value in the rare equivocal stained case. ROS1-rearrangement testing is more cost-effective if immunohistochemistry is followed by fluorescence in situ hybridization after excluding EGFR-mutant and ALK-rearranged adenocarcinomas.

Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution.

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs.

RNA profile of immuno-magnetically enriched lung cancer associated exosomes isolated from clinical samples.

Exosomal cargo secreted from cancer cells has been associated with the development and progression of the tumour. Enriching clinically relevant tissue-specific exosomes may assist in the focused analysis of RNA molecules packaged during cancer. Therefore, this study utilized a rapid immunomagnetic enrichment approach for targeted isolation of lung cancer cell-derived exosomes from human plasma, followed by analysing their cargo RNA using high throughput sequencing. The total RNA purified from these immunomagnetically enriched exosomes provided adequate RNA quality for characterization through the Illumina platform. Differential expression analysis was performed between patients and healthy controls to study the altered exosomal RNA profile during lung cancer. Further, functional enrichment analysis was performed with the list of identified differentially expressed genes (DEGs). In total, 1383 mRNAs and 64 lncRNA were identified as differentially expressed between patient plasma exosomes than healthy controls (fold change > 2, P < 0.05). Kyoto encyclopaedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were mainly associated with cancer-related pathways, purine metabolism, calcium, and cGMP-PKG signalling pathways. In conclusion, the presented approach successfully demonstrated a novel strategy for focused disease-specific transcriptome analysis, which provides a feasible option for identifying disease-specific exosome biomarkers for detecting non-small lung cancer.

Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples.

Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC-MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well.

Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel.

BACKGROUND: Peripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy. OBJECTIVE: To compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. METHODS: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome. CONCLUSION: This study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel. TRIAL REGISTRATION: The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.

Improving the performance status in advanced non-small cell lung cancer patients with chemotherapy (ImPACt trial): a phase 2 study.

PURPOSE: This phase II trial is designed to test whether the performance status (PS) of metastatic non-small cell lung cancer (mNSCLC) patients (pts) can improve with chemotherapy if their poor PS (Eastern Cooperative Oncology Group (ECOG) PS of ≥ 2) is due to disease burden rather than comorbidities. METHODS: Age18-65 years, Charlson's comorbidity index < 9, serum albumin ≥ 3.5 g/dl, adequate bone marrow and organ function, & ECOG PS ≥ 2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60 mg/m2/dose. The primary endpoint was an improvement in ECOG PS by 1 point at 4 weeks; others: toxicity (CTCAE v 5.0), quality of life (QoL) assessment at baseline and 4 weeks by EORTC QLQ-C30 and EORTC QLQ-LC13. Optimal Simon's 2-stage design was used. RESULTS:  Forty-six patients were included with a median age of 56 years (interquartile range, IQR 54-59), 12 (26%) had comorbid conditions, and 87% with ECOG PS 3/4. PS improved in 11 pts at 4 weeks and in 7 beyond this time point. Grade 3/4 toxicities are seen in 20% (most common: anemia and diarrhea). At a median follow-up of 4.8 m (95% CI 3.27-14.9), the median progression-free survival and overall survival were 3.3 months (95% CI 2.36-5.6) and 6.8 months (95% CI 2.47-8.8), respectively. QoL improved for global QoL, role functioning, pain, dyspnea, insomnia, pain in the chest, pain in other parts, and worsened for alopecia and sore mouth. CONCLUSIONS:  Abbreviated chemotherapy is a useful, well-tolerated strategy in carefully selected poor PS mNSCLC patients that can improve PS and QoL. CLINICAL TRIAL: Clinical trial information: CTRI/2020/01/022617.

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome.

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Rapid immunomagnetic co-capture assay for quantification of lung cancer associated exosomes.

Exosomes derived from biological fluids have the potential to serve as a biomarker for the early detection of various cancers. However, the lack of reliable enrichment and detection methods posed a challenge for its clinical utility. In this work, we designed a rapid co-capture-based approach for targeted enrichment and detection of lung cancer-derived exosomes from human plasma. This method relies on the formation of a sandwich complex around the exosomes that involves magnetic nanoparticles coupled to CD151 to assist in the immunomagnetic selection of lung-derived exosomes and a secondary detection antibody (CD81) coupled to horseradish peroxidase for signal amplification. The performance of the co-capture method to detect exosomes has been optimized with known exosome concentrations in human plasma and exhibited good linearity (108-105 exosomes mL-1) with a detection limit of 60.4 exosomes µL-1. This study further investigated the potential of the developed assay to differentiate healthy and lung cancer patients using 18 clinical samples by quantifying the CD151+/ CD81+ lung-derived exosomes. In conclusion, this study demonstrated a rapid co-capture-based approach that offers simultaneous isolation and detection of exosomes compatible with low sample volume for detecting lung cancer patients.

Cost Effectiveness of Ribociclib and Palbociclib in the Second-Line Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer in Post-Menopausal Indian Women.

BACKGROUND: In this study, we evaluate the cost and outcomes of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus fulvestrant, fulvestrant alone, and conventional chemotherapy as the second-line therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in India. METHODS: Using a Markov model, the clinical effectiveness of managing HR+, HER2- MBC in postmenopausal women with either a CDK4/6i (either ribociclib or palbociclib) and fulvestrant, fulvestrant alone, and chemotherapy (single-agent paclitaxel or capecitabine) was measured in terms of quality-adjusted life-years (QALYs). The costs were estimated from two different points of view: scenario I, as per the prevailing market prices of the drugs; and scenario II, as per the reimbursement rates set up by the publicly financed national health insurance scheme. Incremental cost per QALY gained with a given treatment option was compared against the next best alternative and was assessed for cost effectiveness using a threshold of 1-time the per capita gross domestic product (GDP) in India from a societal perspective. RESULTS: In scenario I, an MBC patient was found to incur a lifetime cost of Indian Rupees (₹) 2.54 million ($34,644), ₹2.53 million ($34,496), ₹512,598 ($6,984), ₹326,026 ($4,442) and ₹237,115 ($3,230) for the ribociclib and palbociclib combination arms, fulvestrant monotherapy, single-agent paclitaxel and the single-agent capecitabine treatment arms, respectively. The lifetime cost for CDK4/6i (ribociclib and palbociclib) combination therapy, fulvestrant monotherapy, paclitaxel, and capecitabine arms was estimated to be ₹1.94 million ($26,459), ₹1.92 million ($26,220), ₹315,387 ($4,296), ₹187,392 ($2,553) and ₹153,263 ($2,088), respectively, in scenario II. The mean QALYs lived per MBC patient with CDK4/6i (either ribociclib or palbociclib) combination therapy, fulvestrant, paclitaxel and capecitabine were estimated to be 1.4, 1.0, 0.9 and 0.7, respectively. None of the treatment arms are cost effective at current prices and reimbursement rates at a threshold of 1-time the per capita GDP of India. However, a 78% reduction in the current market price or a 72% reduction in the reimbursement rate of fulvestrant in the government-funded insurance program will make it a cost-effective treatment option for HR+, HER2- MBC patients in India. CONCLUSION: CDK4/6i (ribociclib and palbociclib) therapy is not a cost-effective treatment option for MBC patients. A 72% reduction in the reimbursement rate for fulvestrant monotherapy will make it a cost-effective treatment option in the Indian context.

Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two-six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end-point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression-free survival (PFS), time to progression and overall survival (OS). An intent-to-treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow-up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide-refractory myeloma population.

Severity, Risk Factors and Quality of Life of Patients associated with Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) refers to numbness, tingling, and burning sensation caused by chemotherapy that can cause impairment in Quality of Life (QoL) of the patients. Study assesses severity, risk factors, and quality of life of patients associated with CIPN. A cross sectional descriptive study was conducted at day care ward, tertiary care hospital India. Total of 98 patients receiving paclitaxel for ≥4 months were enrolled by convenient sampling. Data regarding demographics and clinical characteristics, CIPN severity, risk factors, and QoL were collected by structured questionnaires. Study revealed that median score of autonomic symptoms was higher than sensory and motor symptoms. Mean score of FACT/GOG-Ntx sub-domain was 99.05 ± 20.87on a scale of 0 to 152. ECOG Performance status, current exercise behavior, and fruit and vegetable intake was found to be significantly (at p < .05) associated with sensory, motor, and autonomic symptom score. Therefore, CIPN was found to have debilitating effect on QoL.

Treatment outcomes and prognostic factors in locally advanced non-small cell lung cancer - An experience from normal India.

Context: Chemoradiation is the standard of care in locally advanced non-small cell lung cancer (LA-NSCLC). Clinical presentation, disease course, and available treatment options are challenges to overcome. Little is known about the ideal timing and interaction of the two modalities, its relevance in day-to-day decision-making and the treatment outcome. Aims: The study evaluates the demographic profile, treatment pattern, outcome, and radiotherapy (RT) practice and patient care of LA-NSCLC at a tertiary cancer center. Setting and Design: This is a retrospective study from a tertiary cancer centre. Archives of patients of LA-NSCLC treated between June 2016 and June 2018 were included in our study. Materials and Methods: Clinical, demographic characteristics, treatment patterns, and outcomes were recorded. RT practice and patient care process including the integration of RT with other specialties, waiting time, and compliance to treatment were documented and analyzed. Statistical Analysis: Overall survival (OS) and progression-free survival (PFS) were the primary endpoints of the study. Log-rank test was used for univariate analysis for the factors on OS, and Cox's proportional hazards model was used for multivariate analysis for cofactors on OS. Results: Two hundred and thirty-two patients of lung cancer were treated during the study period. Fifty-four patients were squamous cell carcinoma, 108 were adenocarcinoma, and 12 were others. Out of 59 patients of LA-NSCLC, 34 underwent definitive chemoradiation. The median follow-up was 11 months (0.7-29), median overall treatment time was 44 days, median PFS was 8.9 months (range: 1.6-28.6), and median OS was 9.4 months (1.7-44.8). Time to start any oncological intervention was 1 month (0.1-4.3) and time to start RT was 2.1 months (0.1-5.4). Adherence to treatment was 91.2%. Age ≥65 and performance status ≥2 were significant for OS on univariate analysis and none on multivariate analysis. Conclusions: One-third of the cases of NSCLC present in LA stage and a third are suitable for definitive chemoradiation and only 20% undergo the planned treatment.

Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.