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The COVID-19 pandemic has strained the healthcare system worldwide. Our study aimed to evaluate the impact of the COVID-19 pandemic on the diagnosis and surgical care of patients with breast cancer in Amrita Institute of Medical Sciences, Kochi. This is a single-centre retrospective observational cohort study conducted in a tertiary care institution intended to analyse the management of patients with breast cancer before and after the pandemic outbreak. The number of mammograms dropped from 3689 in the pre-pandemic phase to 1901 in the post-pandemic phase, whilst the number of core biopsies remained almost the same (391 before the pandemic and 367 after the pandemic). The number of new patients decreased by 57.7% (from 614 to 354). However, the number of breast cancer surgeries has remained almost the same (318 before the pandemic and 287 after the pandemic). The number of breast conservation surgeries dropped from 127 in 2019 to 93 in 2020 (

Abstract: Von Hippel-Lindau disease is an autosomal dominant disorder characterised by renal cell carcinomas, pancreatic neuroendocrine tumours, central nervous system hemangioblastomas, retinoblastomas, and tumours of the reproductive tract. This disease results from loss of function mutations in the tumour suppressor gene known as the Von Hippel-Lindau gene, located on chromosome 3. Loss of function mutation in the Von Hippel-Lindau gene results in the accumulation of a protein known as a hypoxia-inducible factor, which promotes cellular proliferation and angiogenesis, leading to cancer. Belzutifan inhibits the hypoxia-inducible factor by binding to the Per-ARNT -Sim-B binding pocket on the hypoxia-inducible factor -2α, inhibiting cellular proliferation and angiogenesis. In our thorough literature review, we identified 37 relevant articles. Belzutifan showed clinically meaningful response rates for both Von Hippel-Lindau disease-associated renal cell carcinomas and non-renal cell cancers. The pharmacokinetic profile of belzutifan was much better than its congener molecules due to the optimisation of its dihalide groups from germinal to vicinal. The pharmacodynamic effect of belzutifan was confirmed by its ability to decrease serum erythropoietin, which is a direct result of hypoxia-inducible factor- 2α inhibition. The significant side effects observed were anaemia, hypoxia, fatigue, hypertension, visual impairment and weight gain. Multiple clinical trials are currently underway to determine the role of beluztifan as part of combination regimens in treating Von Hippel-Lindau diseaseassociated malignancies.

Introduction There is high risk of contracting coronavirus disease 2019 (COVID-19) among patients with cancer with risk of mortality and morbidity being high. Limited data is available on the outcomes of universal screening of cancer patients with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from lower-middle-income countries (LMICs). Objectives Our goal was to determine the prevalence of asymptomatic SARS-CoV-2 infection in patients with cancer attending the medical oncology department of a tertiary care hospital in Kerala and protect both patients and health care workers before proceeding with the systemic anticancer treatment. Materials and Methods This was a retrospective cohort study of screening patients receiving systemic anticancer therapy for COVID-19 among hospitalized patients from August 1, 2020, and both outpatients and hospitalized patients from September 1 to November 15, 2020. After clinical triaging, patients were subjected to universal screening with rapid antigen tests and/or reverse transcriptase-polymerase chain reaction (RT-PCR). Results A total of 1,722 SARS-CoV-2 tests (321 RT-PCR and 1,401 antigen tests) were performed among 1,496 asymptomatic patients before their scheduled chemotherapy/immunotherapy. Eight hundred forty-eight patients were screened more than twice. The patient cohort's median age was 59 years (range 01–92 years); 44.98% of patients were males, and 55.01% were females. 58.77% of patients were on adjuvant or neoadjuvant chemotherapy and 41.22% on chemotherapy for metastatic cancer. The most common malignancy was breast cancer (26.53%), followed by lung (8.35%) and gastrointestinal (16.4%) cancers. The prevalence of asymptomatic infections in our study was 0.86%. Only one patient who had undergone chemotherapy after a negative SARS-CoV-2 test developed confirmed COVID-19 during subsequent testing. From these index cases, none of the other patients, health care workers, or their caretakers contracted COVID-19. Conclusion The prevalence of asymptomatic COVID-19 infections in our study was low (0.86%). With proper health education, clinical triaging, and screening of the high-risk group, it is possible to continue cancer treatment during the peak of the COVID-19 pandemic, even in LMICs.

Objectives: Paclitaxel and docetaxel are two commonly used chemotherapeutic agents in the treatment of various types of cancers. However, debilitating taxane-induced arthralgia and myalgia are among the most common adverse reactions associated with taxanes, which has greatly influenced medical practitioners. Most of the mild and moderate analgesics were found to be less effective in the management of taxane induced pain. So we used flupirtine, a non-opioid analgesic, in the treatment of taxane-induced pain. Materials and Methods: In this study, we analysed the baseline pain score and follow-up data of 60 patients receiving a taxane-based chemotherapy regimen. Baseline data of these study populations experiencing significant taxane-induced pain were compared with follow-up data after treating them with analgesic flupirtine (200 mg/day). The baseline and follow-up data representing pain were assessed with the help of the Visual Analogue Scale (VAS), and the quality of life was determined using the Brief Pain Inventory (BPI) scale questionnaire. Results: The mean baseline and follow-up VAS score was compared using paired sample t-test, which showed a significant reduction in taxane-induced pain after treatment with flupirtine (P < 0.001). Similarly, the mean BPI score representing the quality of life before and after treatment with flupirtine was compared, and a notable improvement in quality of life was seen after treatment with flupirtine. The mean and follow-up data of aspartate aminotransferase and alanine aminotransferase levels of patients were also compared to assess the adverse drug reaction profile of the drug, and the analyzed data was found to be statistically insignificant (no significant liver toxicity) which indicates that drug can be used effectively for a period of Conclusion: We believe that flupirtine can be used as an effective analgesic in dire situations where patients require opioid analgesics for the management of taxane-induced pain, provided that the drug is given for

The microsatellite stable (MSS) category accounts for more than four-fifths of colon and rectal cancer (CRC). However, studies during the last two decades in the Indian population have shown that the microsatellite instable (MSI) is more than 30% of CRC cases. We have conducted a study to explore the pathogenesis of microsatellite instability in Indian CRC. In the preliminary studies, we conducted a Nanostring Pan-Cancer pathway analysis of early-stage CRC (n = 10, MSS = 5, MSI = 5) and normal tissues (n=7). We identified the differentially expressed genes associated with the tumor and correlated them against microsatellite instability status. Among them, _AXIN2_, _ETV4_, and _RNF43_ were tumor cell-specific signals that had a differential expression between MSI and MSS groups. When overlapped with the TCGA immune cell infiltration data, TIMER, these genes segregated to the tumor cells. Moreover, they were less associated with other significant genes in protein-protein interaction analysis by STRING. The expression of these genes was further validated in another set of early-stage microsatellite instable CRC (n = 15) by qPCR. The expression fold-changes of these signals suggest distinct subsets in the MSI subgroup of CRC in the Indian population.

Selinexor developed by Karyopharm Therapeutics is the first orally available small-molecule inhibitor of exportin-1 (XPO1). XPO-1 is a protein transporter responsible for the export of macromolecules such as tumor suppressor proteins and oncoprotein mRNAs from the nucleus to the cytoplasm; its inhibition results in blocking of multiple oncogenic pathways. Overexpression of XPO1 is seen in multiple myeloma and various other malignancies and is a poor prognostic marker. Pivotal positive trials have resulted in the approval of selinexor for use in refractory or relapsed diffuse large B cell lymphoma and multiple myeloma. In this review, we briefly cover the drug development, mechanism of action, indications, and toxicities of the drug, and the major pivotal trials.

Aim: To develop a method for making total serum nanoparticles (TSN) loaded with cytotoxic chemodrugs for cancer therapy. Materials & methods: TSN loaded with paclitaxel (PTX) or piperlongumine (PL) were prepared using high-pressure homogenization and tested for immunogenicity in healthy animals and antitumor properties in pancreatic cancer xenograft models. Results: TSN-PL nanoparticles of average size 104 nm and encapsulation efficiency approximately 50% showed enhanced dose-dependent cytotoxicity compared with TSN-PTX or clinically used combination of gemcitabine and nano-PTX in two pancreatic cell lines. Significant antitumor efficacy was also established in the pancreatic xenograft model. Conclusion: We developed a unique method of converting total blood serum into chemo drug-loaded nanoparticles and demonstrated its efficacy in vitro and in vivo.

Background Unmet needs of cancer patients prompt them to seek care from Traditional, Complementary and Alternative Medicine (TCAM) practitioners. Objective To investigate the prevalence of TCAM use in a multi-specialty tertiary cancer center in South India. Materials and methods A cross-sectional survey of cancer patients who used TCAM during the study period. The patients were recruited based on covenience sampling method. Result 320 cancer patients were approached, out of which 279 (87.2%) patients responded, and the prevalence of TCAM use was 34.4%. Home remedies (36%) figure prominently, with family advice (40%) being the primary influence for the TCAM use. The key expectation was an improvement in the quality of life (49%). TCAM use was pronounced during the chemotherapy phase (50%). Most patients (76%) using TCAM reported satisfaction with the treatment. Majority of the patients did not disclose concomitant use of TCAM to their treating physicians (71%). Conclusion TCAM use by cancer patients is prevalent in Kerala. The study results point towards a need for large scale surveys, implementation of pharmacovigilance, patient education and research to identify and integrate TCAM interventions in cancer care that are safe and have beneficial effects.

Epithelioid sarcoma affects three in 10 million people, usually teenagers and young adults. Tumours grow under the skin of the extremities or they can affect the trunk, head, or neck. It grows slowly, but can infiltrate surrounding tissues, later on, it frequently metastasis to lymph nodes. For advanced case, doxorubicin-based chemotherapy regimen is recommended. In January 2020, FDA approved the first-in-class, small molecule enhancer of zeste homolog 2 (EZH2) inhibitor, tazemetostat (Tazverik) to treat adults and paediatric patients aged 16 years and older with locally advanced or metastatic epithelioid sarcoma not suitable for complete resection. The recommended dosage is 800 mg twice daily until disease progression or unacceptable toxicity. The first-in-human study of tazemetostat was a phase 1 open-label multi-centered dose-escalation study. Tazemetostat is having an oral bioavailability of approximately 33%. Apparent volume of distribution at steady-state (Vss/F) is 1230 L (46%) with 88% bound to human plasma proteins. Metabolism takes place via CYP3A. 15% and 79% of radioactivity is excreted through urine and feces respectively. ≥20% of the adverse reactions and above was fatigue, pain, constipation, nausea, anorexia and vomiting. This article summarizes the history, chemistry, physical properties, mechanism of action, indications, and drug–drug interactions of tazemetostat and we also discuss briefly the results of various clinical trials.

Carcinoma of the endometrium is the second most common and the fourth leading cause of mortality due to gynecological cancer among women worldwide. About 80% of endometrial carcinomas present as localized disease and have a 5-year survival rate of more than 95%. Most of the recurrent and metastatic endometrial cancers have a poor prognosis, and the response to chemotherapy is poor. The treatment options for advanced and recurrent endometrial carcinoma are limited. Several trials investigated the role of immune checkpoint inhibitors in endometrial cancer. Based on these trials, pembrolizumab was approved for individuals with unresectable recurrent or metastatic disease. In the current era of advancing immunotherapy, identification of mismatch repair deficiency or microsatellite instability status can predict response to drugs like pembrolizumab. Here, we report a 62-year-old lady with metastatic endometrial cancer who progressed on first-line therapy with lung and lymph nodal metastases. She was oxygen dependent and was bedridden. As she was not fit for chemotherapy, and her MSI status was found to be unstable, she was treated with pembrolizumab and had a remarkable recovery.

Gastrointestinal stromal tumors (GISTs) are rare primary neoplasms of the gastrointestinal tract, mesentery, or omentum. In the past, for patients with resectable tumors, surgery was the only viable treatment option. However, therapy of GISTs has undergone a fundamental change with the advent of receptor tyrosine kinase inhibitors primarily targeting the tyrosine-protein kinase KIT and the platelet-derived growth factor receptor alpha (PDGFRA). Ripretinib is one such novel Type-II tyrosine switch control inhibitor which is used in the treatment of advanced KIT proto-oncogene-driven and PDGFRA-induced tumors, including GISTs. The Food and Drug Administration approved ripretinib on May 15, 2020, for the treatment of adult patients with progressive GISTs who had undergone prior treatment with three or more kinase inhibitors. A comprehensive search in PubMed and other sources were done, using the search terms, “GIST” and ripretinib. On combining all the abstracts and conference proceedings, here we present a comprehensive review on ripretinib's history, pharmacology, and clinical applications.

Nivolumab, a PDL1 antagonist is an immunotherapeutic agent that is effectively used for the second-line treatment of advanced or metastatic lung carcinoma. Although Nivolumab improved the overall survival of patients with non-small cell lung cancers in the setting, it is known to result in adverse events called immune-related adverse events (irAEs) like colitis, pneumonitis, skin disorders, and myasthenia gravis. The majority of cutaneous reactions associated with Nivolumab therapy are Grade 1or Grade 2 but Grade 3 skin reactions are very rare. The grade 3 skin reactions are macules or papules covering >30% of body surface area with moderate or severe symptoms (pruritis, burning, tightness) often impacting the patient’s quality of life. This is a case of a 78-year-old man with Stage 4 metastatic squamous cell lung carcinoma (SqCC), treated with Nivolumab following disease progression after 4 cycles of Paclitaxel / Carboplatin chemotherapy. The patient developed mild hyperpigmentation over the upper and lower limbs after eight cycles of Nivolumab, which progressed to Grade 3 skin reaction with intense pruritis after the eleventh cycle. He was treated with systemic steroids and Nivolumab was discontinued after which the patient’s condition improved. Health care professionals should be aware of the immunological side effect profile of Nivolumab. Close monitoring, periodic dermatological evaluation, and appropriate clinical management is recommended in patients on immunotherapy.

Background Multiple acyl-CoA dehydrogenase deficiency (MAAD) is a rare metabolic disorder resulting from an abnormality in fatty acid oxidation. There are three types of presentations: neonatal onset with or without congenital anomalies and the late-onset type. There is much clinical heterogeneity in the presentation of late-onset variants; hence, the diagnosis is often delayed or missed. Case presentation Here, we report the successful management of a 41-year-old female with late-onset MAAD due to mutation in the ETFDH gene who presented with carcinoma of the breast. Chemotherapy was challenging because there were no previous reports regarding the treatment of such cases. Conclusion The diagnosis was made based on metabolic workup and gene mutation analysis. Unplanned surgery and chemotherapy can be fatal in these patients due to metabolic complications. With proper precautions and monitoring, the patient tolerated surgery and chemotherapy without any complications.

The global incidence of lung cancer among women is rising. By 2030, lung cancer in women is expected to increase by 43%. The factors thought to predispose women to lung cancer are exposure second hand smoke, air pollution and biofuels used for cooking. Our objectives was to study the clinical and pathological features of lung cancer in women. Material: A retrospective review of medical records of women with lung cancer who attended Amrita institute of medical sciences, Kochi, between 2015-2019 was done. Data was collected using our institution's Electronic medical records (EMR). Demographic details and clinicopathologic features were extracted from the EMR manually. Data was tabulated using Microsoft Excel. Categorical variables were expressed as frequencies and percentages., Observation :Out of the 1683 lung cancer cases seen during 2015-2019, 389 (23.1%) were females. 250 patients for whom complete data was available was included in this study. Majority of the women were above 50 years old (N= 216, 86.4%). The median age of diagnosis was 64 years (range 33- 95 years). 14 patients (5.0%) had history of pulmonary tuberculosis. The median duration of symptoms was 8.7 weeks (IQR 4.3 -13). Cough (N=173, 69.2%), dyspnoea (N=117, 46.8%) and chest pain (N = 105, 42%) were the most common symptoms. Data regarding the use of cooking medium used (biofuel/LPG) was available only in 107 patients. 15/107 (14%) patients were using biofuels for cooking. 75.2% of them presented in advanced stages (Stage IV N=188). The most common sites of metastasis were bone (N=88, 35.2 %), lung (N = 55, 22%), lymph nodes (N=55, 22%) brain (N= 38, N= 15.2%), liver (N=32, 12.8%) and adrenal gland (N=31, 12.4%). 113 patients had one and 77 patients had multiple metastatic sites. The site of primary tumour was-right upper lobe N=67 (26.8%), Right middle lobe N =11 (4.4 %%), Right Lower lobe N=46 (18.4%), Left upper lobe N=65 (25%) and left lower lobe N=52(20.8%). Adenocarcinoma was the predominant histological type (N=224, 89.6%) followed by squamous cell carcinoma (N=12, 4.8%). Actionable mutations observed were EGFR in 44% and ALK 2% and BRAF 1.2%. Conclusion: Male to female ratio in our study (4.3:1) was higher compared to the lung cancer demographics from other states in India. This finding along with rising global incidence warrants special attention and screening for women with suspicious symptoms. The incidence of EGFR mutation was also high (44%) compared to other studies from India.

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-β family, TGF-β1 modulates most of its biological outcomes. Despite the abundant expression of TGF-β1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-β1 levels, contributing to poor prognosis and survival. Additionally, elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage

Abstract: The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetics) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-sizefits- all-fixed-dosing approach. Therapeutic drug use can be monitored based on pharmacokinetic, pharmacodynamic, and pharmacometric methods. Based on the experiences of therapeutic drug monitoring of various agents across the globe, we can look ahead to the possible developments of therapeutic drug monitoring in India.

The prevalence of microsatellite instability and deoxyribonucleic acid mismatch repair deficiency in colorectal adenocarcinoma (CRC) cases is higher in India compared to western populations. No major study on the molecular pathogenesis is currently available in the Indian population. We conducted a pilot study to explore the differences in molecular pathogenesis of microsatellite stable (MSS) and microsatellite unstable CRC from a tertiary care centre in Kerala, South India. Using Nanostring PanCancer panel assay in Stage II colorectal adenocarcinoma, tumour tissues (n = 11) were compared against normal colon tissues (n = 4). Differentially expressed (DE) genes were identified and super-imposed onto colon adenocarcinoma cohort of The Cancer Genome Atlas (TCGA) data (TCGA Colon Adenocarcinoma (TCGA COAD)), from the Genome Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource (TIMER) to compare the gene associations. Significant DE genes were 59 out of 730 (false discovery rate adj. p-value < 0.05), 18 of which had a fold-change |FC(log2)| ≥ 2. On superimposition to TCGA COAD, 33 genes were significant in both TCGA and current study. ETV4 was expressed significantly higher in MSS with no immune cell infiltration. Other significant DE genes with high FC(log2), unique to the study were INHBA, COL1A1, COL11A1, COMP, SFRP4 and SPP1, which were clustered in STRING network analysis and correlated with tumour-infiltrating immune cells in TIMER, suggesting a specific interaction pathway. The preliminary study suggests a distinct pathogenesis of MSS CRC involving ETV4 in the Indian population and warrants further clinically extensive and high-dimensional expression studies.

BackgroundNanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene-targeted siRNA nanoparticle gel (NPG) for the combinatorial silencing of 3 aberrant genes, thus inhibiting the tumorogenic potential of GSCs.MethodsNPG loaded with siRNAs targeted against FAK, NOTCH-1, and SOX-2 were prepared by the self-assembly of siRNAs with protamine–hyaluronic acid combination. Electron microscopy, DLS, and agarose gel electrophoresis were used for the physicochemical characterization. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma-derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-derived xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity.ResultsThe siRNA nanoparticles with an average size ~ 250 nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumor growth in orthotopic rat brain tumor model.ConclusionIntracranially injectable n-siRNA NPG targeted to multiple stem-cell signaling impairs glioma initiation capabilities of GSCs and inhibited tumor growth in vivo.

Gastrointestinal stromal tumours are rare neoplasms of the gastrointestinal tract that are mesenchymal in origin. The introduction of tyrosine kinase inhibitors resulted in significant improvement in survival of patients with gastrointestinal stromal tumour even in advanced disease conditions. A 43-year-old adult male who is a known case of gastrointestinal stromal tumour of the stomach, on adjuvant therapy with imatinib, presented with a history of gross haematuria of several episodes as well as persistent microhaematuria and was evaluated for the same. He was investigated for all possible causes, but all were negative. The patient was advised to withhold imatinib. Haematuria resolved 1 month after stopping imatinib. Then it was rechallenged. He had recurrence of symptoms, so it was discontinued. In view of the temporal relation of haematuria and administration of imatinib, a diagnosis of imatinib-induced haematuria was made.

Patients with severe mental illness (SMI) face health inequalities that lead to under treatment of diseases such as cancer and result in increased mortality. There is literature addressing this issue for SMI patients in high-income countries but few for those in low- and middle-income countries. This review aims to draw attention to the health inequalities and the compounding factors faced by SMI patients in low- and middle-income countries. The relevance of integration of psycho-oncology in the care of SMI patients with cancer is integral to reduce disparities and address varied contributory factors.The literature review was conducted by searching through two databases which includes PubMed and Google Scholar. We searched for articles using keyword search terms: severe mental illness, SMI, schizophrenia, bipolar disorder, cancer, low- middle-income countries, low- and middle-income countries, psycho-oncology, HPV vaccine, cancer incidence, cancer mortality, cancer control, cancer screening, cancer treatment and palliative care.A total of 80 research articles were included in our literature review. We found that there was an increased requirement for adapting to the changing disease landscape in low- and middle-income countries. An improvement on aspects such as vaccination, screening and prevention is necessary, and also efforts to change social stance towards SMI is crucial.There is an increase incidence of cancer in low- and middle-income countries, and the number of patients with SMI in low- and middle-income countries is also rising. This is due to social, psychological, economical and healthcare factors. Low- and middle-income countries must consider improving these aspects in order to adapt to the changing landscape.

The purpose of the study was to investigate the value of pretreatment neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in triple-negative breast cancer (TNBC) and to see its bearing on the clinical and pathological stage of the disease.This was a retrospective analysis of cases of TNBC treated at our center from 2006 to 2013. The pretreatment complete blood count was recorded from which the NLR was calculated as the percentage of neutrophils divided by the percentage of lymphocytes. The association between pretreatment NLR with the stage of the disease, clinical and pathological lymph node status, and disease-specific survival was analyzed.A total of 208 patients were eligible for the analysis. The median follow-up period was 48 months. The NLR was found to have a strong correlation with the pathological nodal status and the clinical stage (75% cases node-positive in the high NLR group versus 36% in the low NLR group; P0.01). At the time of analysis, 74% of our study population was alive and well. There was no significant correlation between the NLR and the overall survival.Based on our study, we conclude that the pretreatment NLR is strongly associated with lymph node metastasis and clinical stage in TNBC patients. It is probably not useful as a prognostic marker, as it does not seem to have any significant bearing on the overall survival.

The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34

Leptomeningeal carcinomatosis (LC) is the metastatic infiltration of leptomeninges by malignant cells originating from an extrameningeal primary tumor site, either extraneural or intraneural. In the absence of treatment, survival is usually measured in weeks, however with treatment this may be extended to a few months. Our institutional protocol has been to offer intrathecal chemotherapy (ITC) to patients having solid tumors with cerebrospinal fluid (CSF) cytology positive leptomeningeal carcinomatosis. This study was performed to describe the oncological outcomes in this cohort and their determinants.A retrospective review of data of patients treated at Amrita Institute of Medical Sciences, Kochi, India was performed. Patients with CSF cytology positive solid tumors treated with triple ITC (methotrexate, cytosine arabinoside and hydrocortisone) were assessed for patient characteristics, treatment response, survival and the factors affecting them.Twenty patients of LC treated with triple ITC were included in the study. The median age of the study group was 49 years with a slight female preponderance (55%). All patients had positive CSF cytology with mean CSF glucose of 60 mg/dL, mean CSF protein of 92 mg/dL and mean cell count of 5. Breast cancer was the most common primary tumor (45%), followed by lung (35%) and stomach (5%). Symptomatic improvement was reported in 70% of patients after initiating ITC. Median overall survival (OS) at 6 and 12 months was 38% and 14%, respectively. Median progression-free survival (PFS) was 2 months. Patients with brain parenchymal metastasis had poor 6 month OS (25% vs 50%, P = 0.013) and 6 month PFS (0% vs 20%, P = 0.023).A triple drug combination of methotrexate, cytosine arabinoside and hydrocortisone when given intrathecally for patients with LC showed good control of symptoms and reasonable survival. It may be beneficial in patients with no brain parenchymal involvement.

A number of patients with advanced-stage epithelial ovarian cancer do survive beyond 5 years. The long-term follow-up data are limited, especially for the Indian setting. We evaluated the 10-year survival outcome and influencing clinicopathological factors.A retrospective analysis of advanced-stage epithelial ovarian cancer patients who underwent primary cytoreductive surgery (PCS) or interval cytoreductive surgery (ICS) from 2005 to 2008 was conducted. Survival analysis was performed with the Kaplan-Meier method, and the Cox proportional hazards model was used for prognostic clinicopathological factors analysis.Ninety-four patients with a median age of 54.5 (18-79) years were evaluated. The median follow-up period was 11.2 years. The overall survival (OS) rates at 5, 7, and 10 years were 37%, 23%, and 18%, respectively. The median OS (MOS) was 46 (95% confidence interval [CI], 36-55.8) months and progression-free survival (PFS) was 19.5 (15.3-23.6) months. Long-term survival was significantly predicted by R0 resection (complete cytoreduction with no macroscopic residual disease) and PFS20 months while prolonged PFS was influenced by age ≤55 years and R0 resection. For the R0 resection group, patients who underwent PCS had better overall survival in comparison with ICS [72.1(25.2-119) months vs 47.4 (34.9-59.9)months] on 10 years follow-up but was not significant statistically.Patients with age ≤55 years, R0 resection, PFS20 months have a better 10-year survival outcome. Among R0 resection, patients undergoing PCS have clinically a better outcome on 10-year follow-up.

Extramedullary plasmacytoma (EMP) is an uncommon presentation and usually occurs in conjunction with multiple myeloma (MM). An EMP without developing MM at any point is an extremely rare presentation, and only seven such cases have been reported in the literature to date.We present a case of EMP, who presented with multiple recurrent lesions in rare sites like nasal cavity, testis and skin without the involvement of bone marrow at any point of disease course. He was treated with multiagent chemotherapy (DT-PACE) and continues to be in remission at 29 months post-chemotherapy, which is the longest amongst all the cases reported so far.There are no clearly defined guidelines to treat EMP. Our case had a clinical presentation at very unusual sites and was treated with DT-PACE regimen as against the previous seven reported cases and had the most prolonged period of remission.

Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma occurring among predominantly adolescent and young adult men, accounting for 1%–2% of all non-Hodgkin's lymphomas. In contrast to B-LBL, T-cell LBL is much more common, accounting for up to 90% of disease in adults. Mediastinal mass, pleural and/or pericardial effusions are the major characteristics of T-LBL. We report an 27-year-old male with a pleural effusion, mediastinal lymphadenitis, and a normal hemogram. The cytology of the pleural effusion initially was lymphocytic exudative and ADA was high. For definitive diagnosis a medical thoracoscopy was done. The partial pleura showed multiple irregular nodules and thickening in sheets. It was picked and immunophenotypic study revealed the following: CD3, TdTþ, CD7 with Ki 67 index of 70–80%. The patient was finally diagnosed with T-LBL. He was treated with chemotherapy and is on regular follow up with resolution of effusion. The case highlight the point that medical thoracoscopy is a safe and accurate diagnostic procedure for pleural diseases, and partial pleura biopsy yielded the correct diagnosis.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among women in India; however, there are no studies addressing long-term survival (10 years and above). This study sought to evaluate long-term oncological outcome among women with breast cancer treated with a curative intent. MATERIALS AND METHODS: This is a retrospective cohort analysis of 1301 breast cancer patients of all stages who had received primary treatment with curative intent from 2004 to 2010 at a single cancer institution of India. RESULTS: A total of 1301 breast cancer patients were available for final analysis. The median age was 51 years (range, 21–86 years). 70.25% of the patients had early breast cancer (EBC), 21.9% had locally advanced breast cancer, and 7.85% of the patients with de novo metastatic disease also underwent surgery. 56.5% of the patients had hormone-sensitive tumors, human epidermal growth factor receptor 2 over expression was seen in 17%, and triple-negative tumors accounted for 26.2% of the patients. The 5- and 10-year overall survival (OS) of the entire cohort was 79% and 66%, and the 5- and 10-year breast cancer-specific survival (BCSS) was 79% and 70%, respectively. OS and BCSS were 51% and 58%, respectively, at 15-year follow-up after primary cancer treatment. On multivariate analysis, the factors associated with prolonged survival were age ≤50 years, EBC, and treatment during the later period (2008–2010). CONCLUSION: Difference between OS and BCSS was found to have an increasing trend during 10–15-year follow-up, the difference being 4% at 10 years and 7% at 15 years. Age ≤50 years, early-stage disease at presentation, and primary cancer treatment in later years (2008–2010) were favorable predictors for 10-year survival.

High throughput somatic expression analyses of colon adenocarcinoma conducted so far were mostly in the western population, and no major studies are currently available in the Indian population. We have performed Nanostring PanCancer pathway panel assay in Stage II colon cancer (n = 11) and compared against normal colon tissues (n = 4). Differentially expressed (DE) genes were identified and superimposed on the Cancer Genome Atlas (TCGA) data, from the Genome Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER).83 out of 730 genes were significantly different (p-value < 0.01), 19 of which had a fold-change |FC(log2)| ≥ 2. A comparison of these signals on TCGA COAD data revealed four common (MET, MCM2, ETV4, and MMP7) and15 uncommon genes. On group comparison, ETV4 expression was significantly higher in microsatellite stable (MSS). Significant DE genes, unique in the study, were INHBA, COL1A1, COL11A1, COMP, SFRP4, and SPP1, which were clustered in STRING.db network analysis and correlated with tumor-infiltrating immune cells in TIMER.MMR functions of colon cancer pathogenesis in India may be differentiated by validating the somatic expression of most common genes identified in the study.

Isolated Splenic metastasis from ovarian cancer rarely occurs with only very few cases recorded in the literature. It can occur as a synchronous metastasis or as late as 20 years post-primary debulking surgery. A 62-year-old woman with carcinoma ovary stage IIIC was treated with primary debulking surgery in 2009, followed by six cycles of chemotherapy. In 2013, she was found to have an elevated serum CA-125 level during her regular follow-up. Imaging with CT scan abdomen showed a hyperdense lesion in splenic parenchyma of 2.1 × 2.4 cm. She underwent laparoscopic splenectomy. Histopathological examination revealed adenocarcinoma localised to the spleen, consistent with metastasis carcinoma ovary. Post-splenectomy, her CA-125 level returned to normal. Over the last 6 years, she is on regular follow-up and remains disease-free. Isolated, solitary splenic metastasis from epithelial ovarian cancer is very rare. It occurred after a DFI of 4 years and was successfully treated and is remaining disease-free without any chemotherapy for the last 7 years.

Neuroendocrine tumours can originate from any part of the body. The most common site in the head and neck is the larynx, accounts for less than 0.6%. The neuroendocrine carcinomas (NECs) of the larynx are rare tumours with high incidence of widespread metastases and poor prognosis. Here we report a 50-year-old male with localised primary moderately differentiated NEC of the larynx. He was treated with surgery followed by adjuvant chemotherapy and concurrent chemoradiation. He is free of his disease and is doing well.

Clinico-pathological differences between adenocarcinoma in the right and left colo-rectum play a role in determining the prognosis and response to treatment. Studies suggest that primary tumor location is more relevant as the disease progresses and reflects a possible difference in biology and response to therapy. This review aims to explore the clinico-pathological features of right and left colo-rectum and the impact of primary tumor location on prognosis of CRC as well as discuss the available clinical data on tumor sidedness in metastatic colorectal cancer. In so far as the clinical data of tumor sidedness is concerned, very few reviews have discussed the clinical implications of sidedness in heavily pre-treated metastatic colorectal cancer (second and subsequent lines of therapy in metastatic disease). This review aims to fill the current gap in this setting.

BCR-ABL fusion protein drives chronic myeloid leukemia (CML) which constitutively activates tyrosine kinase involved in the initiation and maintenance of CML phenotype. Ponatinib, an oral drug, was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib, were used to develop a robust two-dimensional quantitative structure–activity relationship (2D-QSAR) and 3D-Pharmacophore models by dividing dataset into 32 training sets and 12 test set molecules. 2D-QSAR model was developed using Genetic Function Approximation (GFA) algorithm consisting of four types of information-rich molecular descriptors, electrotopological (ES_Count_aasN and ES_Sum_aaaC), electronic (Dipole_X), spatial (PMI_Y) and thermodynamic (LogD), primarily contributing to BCR-ABL kinase inhibitory activity. For the best 2D-QSAR model, the statistics were R2 = 0.8707, R2pred = 0.8142 and N = 32 for the training set molecules. Phase module of Schrödinger suit was employed for 3D-Pharmacophore model development showing five different pharmacophoric features – ADHHPRR with good R2 of 0.9629, F of 175.3, Q2 of 0.645 and root-mean-square error (RMSE) of 0.214 that are essential for an effective BCR-ABL kinase inhibition. These two models were further validated by cross-validation, test set predictions, enrichment factor calculations and predictions based on the external dataset. The molecular mechanism of resistance arising due to gate keeper mutation T315I of ABL kinase in complex with its inhibitors was also studied using molecular docking and molecular dynamics simulations. Our developed models predicted key chemical features for designing potent inhibitors against BCR-ABL kinase activity and its resistance mechanism to CML disease therapy. Communicated by Ramaswamy H. Sarma

A woven nanotextile implant was developed and optimized for long-term continuous drug delivery for potential oncological applications. Electrospun polydioxanone (PDS) nanoyarns, which are twisted bundles of PDS nanofibres, were loaded with paclitaxel (PTX) and woven into nanotextiles of different packing densities. A mechanistic modeling of in vitro drug release proved that a combination of diffusion and matrix degradation controlled the slow PTX-release from a nanoyarn, emphasizing the role of nanostructure in modulating release kinetics. Woven nanotextiles, through variations in its packing density and thereby architecture, demonstrated tuneable PTX-release. In vivo PTX-release, pharmacokinetics and biodistribution were evaluated in healthy BALB/c mice by suturing the nanotextile to peritoneal wall. The slow and metronomic PTX-release for 60 days from the loosely woven implant was extremely effective in enhancing its residence in peritoneum, in contrast to intraperitoneal injections. Such an implantable matrix offers a novel platform for therapy of solid tumors over prolonged durations.

Background & objectives: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been evaluated in patients with advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib are the first-generation EGFR-TKIs for patients with NSCLC. However, there is a paucity of studies comparing the effectiveness of these two drugs. Hence, this study was aimed to compare the effectiveness and safety of erlotinib and gefitinib in NSCLC patients. Methods: This study included 71 NSCLC patients who received EGFR-TKIs between 2013 and 2016. Adverse drug reaction of both erlotinib (n=37) and gefitinib (n=34) was determined and graded according to Common Terminology Criteria for Adverse Events grading system. Effectiveness was measured using response evaluation criteria in solid tumours and progression-free survival (PFS). Pharmacoeconomic analysis was performed by cost-effective analysis. Results: When comparing safety profile, both the drugs had similar adverse events except for dermal side effects such as acneiform eruption (51.4%), rash (54.05%) and mucositis (59.5%) for erlotinib and 20.6, 26.5 and 29.4 per cent for gefitinib, respectively. The PFS of the two drugs was compared to differentiate the effectiveness of erlotinib and gefitinib. There was no significant difference between the effectiveness of the two drugs. The pharmacoeconomic analysis showed that gefitinib was more cost-effective than erlotinib. Interpretation & conclusions: This study showed that erlotinib and gefitinib had similar effectiveness but gefitinib had a better safety profile compared to erlotinib. Therefore, gefitinib could be considered a better option for NSCLC patients compared to erlotinib. However, further studies need to be done with a large sample to confirm these findings.

Lung adenocarcinoma, the most widespread cause of neoplasm associated mortality in both men and women worldwide, is a subtype of non-small cell lung cancer (NSCLC). We address here the case of a 62-year-old female presented with symptoms of cough and breathlessness of 2-months duration. Histopathological examination of lung biopsy and immunohistochemical tests revealed lung adenocarcinoma. Integrated positron emission tomography-computed tomography (PET-CT) scan suggested right lung lesion with stage 4 (T3N3M1b) disease. Epidermal growth factor receptor (EGFR) mutation analysis was positive for exon-19 deletion mutation, and she was started on afatinib 40 mg once daily. PET-CT scan, at 6-months follow-up, was suggestive of complete response to therapy. Due to drug-induced persistent diarrhea, afatinib was discontinued by the patient, but a repeat PET-CT scan 6 months after discontinuation of treatment suggested disease recurrence. However, T790M-resistant mutation analysis was found to be negative, and she was restarted on afatinib at 30 mg once daily to minimize the drug-related diarrhea. After 15 months of afatinib therapy at reduced dosage, reevaluation by PET-CT suggested disease progression. Although afatinib monotherapy is effective in EGFR exon-19 deletion mutation NSCLC, this report suggests that discontinuation of the drug can lead to disease recurrence, and reducing the drug dose is not beneficial once disease recurrence occurs. To the best of our knowledge, this is the first reported case from India of advanced lung adenocarcinoma of EGFR exon-19 deletion showing a complete response to afatinib and recurrence of the disease after discontinuation of drug.

Human epidermal growth factor receptor 2 (HER2)-positive is an aggressive subtype of breast cancer and has historically been associated with poor outcomes. The availability of various anti-HER2 therapies, including trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (TDM-1), has remarkably improved the clinical outcomes in patients with HER2-positive metastatic breast cancer (mBC). However, there is a need to optimize treatment within this population, given the wide variability in clinical presentation. Additionally, geographical and socio-economic considerations too need to be taken into account. To clarify and collate evidence pertaining to HER2-positive metastatic breast cancer, a panel of medical and clinical oncologists from across India developed representative clinical scenarios commonly encountered in clinical practice in the country. This was followed by two meetings wherein each clinical scenario was discussed in detail and relevant evidence appraised. The result of this process is presented in this manuscript as evidence followed by therapeutic recommendations of this panel for management of HER2-positive mBC in the Indian population.

Sarcoidosis is a multi-system granulomatous disorder characterized by involvement of multiple systems with or without lymphadenitis. Pulmonary complications are common and may lead to morbidity. Breast cancer is one of the commonest malignancy among women across the world. There is an increased risk of malignancies in sarcoidosis. This association with cancer creates a diagnostic dilemma due to the predominant involvement of nodes and organ systems in both conditions. Here we report three cases of sarcoidosis with breast cancer diagnosed over one year.

Purpose: We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment. Methods: This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011. Treatment included lenalidomide 25 mg daily for 21 days, with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle, for 6 cycles. Response was evaluated after the 3rd and 6th cycles of treatment. All patients were followed for 5 years. Results: The study enrolled 51 patients. Median age in the group was 61 years (range: 38–76 years). Immunoglobulin G or A myeloma constituted 70.6% of the diagnoses, and light-chain myeloma constituted 29.4%. Stages I, II, and III (International Staging System) disease constituted 21.4%, 28.6%, and 50% of the diagnoses respectively. All patients were transplantation-eligible, but 34 (66.7%) refused for economic reasons. After treatment, 19.6% of the patients achieved a stringent complete response; 35.3%, a complete response; 5.9%, a very good partial response; and 29.4%, a partial response, for an overall response rate of 90.2%. Stable disease was seen in 3.9% of patients, and progressive disease, in 5.9%. Grade 3 or greater nonhematologic and hematologic toxicity occurred in 35.2% and 11.7% of patients respectively. Pulmonary embolism occurred in 1 patient. No patient experienced deep-vein thrombosis or peripheral neuropathy. The median follow-up duration was 66 months. All patients experienced disease progression. Median progression-free survival was 16 months. In 10 patients, re-challenge with lenalidomide and dexamethasone achieved a second complete response. At the time of writing, 19 patients had died. The overall survival rate at 5 years was 62.74%. Median overall survival is not yet reached. Conclusions: In a resource-constrained setting, lenalidomide with low-dose dexamethasone is an effective treatment with acceptable toxicity in patients newly diagnosed with multiple myeloma and not planned for transplantation. Complete responses were significantly more frequent than reported in the Western literature. Occurrence of clinical deep-vein thrombosis was rare, but hyperglycemia was common. An abbreviated course of treatment is suboptimal in multiple myeloma. Maintenance regimens should be advocated.

Background: Breast cancer is a heterogeneous group of disease, and recently, intrinsic sub-typing on the basis of gene expression profiling is found to be a predictor of breast cancer clinical course. The St. Gallen has released surrogate classification for breast cancer sub-types depending on immunohistochemistry (IHC) markers. Aim: The aim of our study was to analyze the distribution of sub-types using IHC surrogate markers in our patient population and to assess the clinico-pathological factors in different sub-types. Materials and Methods:A total of 635 non-metastatic patients who underwent radical intend treatment from January 2011 to December 2013 were included for this retrospective analysis. A statistical analysis was done by Windows SPSS version 20. The Chi-square test was used to examine the correlations of these sub-types with clinico-pathological parameters. The Kaplan-Meier method estimates were used for survival analysis. Results: The median follow-up was 42.77 months (5 months to 112 months). Luminal B was the predominant group. Disease free survival (DFS) at 5 years was 95% in luminal A, 78% in luminal B HER-2 negative, 80% in luminal B HER-2 positive, 72% in triple negative, and 79% in HER-2/neu non-luminal. Tumor size, Ki67, T stage, N stage, and grade were significantly associated with DFS in all biological type with a P value of less than 0.05. Conclusion: Surrogate classification was successfully applied in our patient cohort. Luminal B and triple negative sub-groups were more prevalent in our patients, and this finding is at variance with published international data. Biological sub-type also emerged as an important predictor of survival.

To investigate the prognostic value of lymph node ratio (LNR) after neoadjuvant chemotherapy (NAC) according to breast cancer molecular subtypes.From 2004 to 2014, patients with definitive surgery after NAC were identified. LNR was calculated for node positive patients who underwent axillary dissection and at least 10 nodes (LNT) were removed. Disease free and overall survivals were analysed using Kaplan-Meier test and compared using log rank test for ypN0-3, LNR categories (LNRC) ≤0.2 (low), 0.21-0.65 (intermediate),0.65 (high), and single LNR cut-off value.Of 224 analysed patients: ypN0 72 (32.1%), ypN+ 152 (67.9%). Of 118 LNT ≥10 ypN+ patients LNRC: Low risk 48 (40.7%), intermediate risk 36 (30.5%), high risk 34 (28.8%). Factors significantly different in LNR categories were ypN (P0.001); extranodal extension (P0.001); present status of patients (P0.001); and disease status (P = 0.029). LNRC was inversely associated with 5-year DFS: Low 52.3%, intermediate 40%, and high 12.2% (log rank P0.001); and OS: Low 64.4%, intermediate 58.3%, and high 13.6% (log rank P0.001). Significant association of LNRC and DFS and OS were demonstrated in TNBC (P0.001) and HER2 subtypes (P = 0.045 and 0.005 respectively). A single value of LNR = 0.25 in node positive was found significant for DFS and OS in TNBC (P0.001) and Her2+ (P = 0.013 and P = 0.001 respectively) but not for HR+ (DFS: P = 0.132; OS: P = 0.144).Residual nodal disease after NAC analysed by LNRC or LNR = 0.25 cut-off value, is prognostic and can discriminate between favourable and unfavourable outcomes for TNBC and Her2+ breast cancers.