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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.

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.

Background: The incidence of CCA in India is on the rise especially in Kerala. However, the clinical profile and outcome of these patients has never been reported. The aim of this study was to identify region specific epidemiological trends and natural history of CCA in Kerala.Methods: This was a single centre, hospital based epidemiology study where incident cases of CCA from January 2014 to August 2016 were studied. Patient demographics and relevant clinical and laboratory data, imaging studies and treatment, were recorded in a predesigned Performa.Results: A total of 137 patients (mean age 62.92 ± 12.5 years, M:F=1.2) were studied of which 109 patients had Hilar CCA (pCCA), 16 patients had Distal CCA (dCCA) and 12 patients had Intrahepatic CCA (iCCA). A majority of patients were from coastal areas and rubber plantations. Known risk factors were absent in our patients. Bismuth Type IV disease was seen in 55 patients (50.5%). Most intrahepatic CCA (iCCA) (7/12) patients had stage IV disease at presentation. Curative resection was possible in 17/38 patients (44.7%). Patients who underwent treatment with a curative intent were younger with less advanced disease and therefore, had a significant 3 month, 6 month and 1 year survival advantage (p

e15517 Background: DPYD deficiency is present in 3-5% of patients. The risk of treatment-related death in DPYD mutation carriers who receive fluoropyrimidine chemotherapy has been estimated at 3-10%. There is growing data in support of widespread screening for DPYD deficiency prior to fluoropyrimidine chemotherapy. The purpose of our study was to identify the prevalence of DPYD deficiency among patients receiving 5-fluorouracil (5FU) or capecitabine based combination chemotherapy, and to analyse the toxicity profile among the DPYD deficient group. Methods: The study involved patients who have received 5FU and capecitabine based chemotherapy for the treatment for gastrointestinal, breast and head and neck cancers between 2019-2020. Four DPYD variants were checked using real-time PCR based Genotyping assay. Three common DPYD variants recommended by the CPIC guidelines (IVS14+1 G>A (*2A), c.1679T>G (*13), c.2846A>T) and a common variant in Asian population (c.496A>G), based on previous studies, was included in our analysis. These variants were assessed prior to the initiation of the chemotherapy and dose was modified based on the activity score and the toxicity profile was assessed. Descriptive statistics was performed using SPSS version 20. Results: 375 patients were included in this analysis. The median age of the cohort was 61years (21-84 years). 51.3% were males and 49.7% females. Among the 375 patients, 47 patients had DPYD mutation (12.5%). The median age of the DPYD mutated patients were 68 years; 29 (61.7%) males and 18 (38.2%) females. 32 (68.8%) had deleterious mutation in DPYD variant c.496A>G (rs2297595) and 15 (31.9%) showed mutation IVS14+1 G>A (rs3918290). 35 out 47 patients had grade II-III toxicity even after dose reduction during the first cycle of chemotherapy. The commonly seen adverse events were hand and foot syndrome in 18 (38.3%), mucositis in 7 (14.9%), diarrrhoea in 15 (31.9%) and neutropenia in 25 (31.9%) patients. Four patients had febrile neutropenia. One patient experience myocardial infarction. There was no mortality. Chi square analysis showed DPYD mutation had significant association with presence of severe adverse reaction (74.5%, p-value. 0.002). Conclusions: Prevalence of DPYD mutation in our patients was 12.5%. They experienced more toxicities while receiving 5-FU/Capecitabine even after dose modification. c.496A>G (rs2297595) was the most common variant seen in our patients. Screening of patients for DPYD mutations prior to administration of 5-FU/capecitabine using pharmacogenetic methods may help identify those patients who are at risk for adverse effects, allowing a more individualized approach to their chemotherapy management. c.496A>G (rs2297595) variant should also be in included routinely in DPYD screening among South Asian population.

The purpose of this study was to correlate the pattern of spread with oncological outcomes in advanced ovarian cancer patients. This is a retrospective analysis of 55 consecutive patients who had advanced epithelial ovarian cancer or primary peritoneal carcinomatosis (stages 3C and 4) with primary surgical intervention as the initial modality of treatment. Based on the spread of disease, they were further classified into class A: disease confined to the pelvis (excluded); class B: disease extending to the lower abdomen and omentum; class C: diffuse small-bowel disease with or without A, B, or D; and class D: disease in the upper abdomen. There were 17 patients (30.9%) in class B, 17 (30.9%) in class C, and 21 (38.2%) in class D. The number of patients with suboptimal cytoreduction was highest in class C (six patients). At the end of follow-up (median 38.6 months), 16 patients had no evidence of disease and 26 patients were alive with disease. The 3-year overall survival rates in classes B, C, and D were 94.1, 52.5, and 93.3%, respectively. The 3-year progression-free survival rates were 55.8, 11.8, and 41.9%, respectively. The rates were lowest for class C. The differences in the overall survival rate (p