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Coronavirus pandemic has increased human disease burden, as well as economic distress globally. Being in an immunocompromised state, patients with cancer comprise an important at-risk population for novel coronavirus disease 2019 (COVID-19) infection. It is necessary to modify individualized clinical management for every cancer patient in the context of the ongoing COVID-19 pandemic. Simultaneously, additional safety precautions for the cancer care providers are mandatory. This review will provide general recommendations in the Indian context optimizing the same.

Nuclear respiratory factor 1 (NRF1) drives estrogen-dependent breast tumorigenesis. Herein we examined the impact of NRF1 activity on the aggressiveness and disparate molecular signature of breast cancer in Black, White, Asian, and Hispanic women. NRF1 activity by transcription factor target enrichment analysis and causal NRF1-target gene signatures by Bayesian Network Inference with Java Objects (BANJO) and Markov Chain Monte Carlo (MCMC)-based gene order were examined in The Cancer Genome Atlas (TCGA) breast cancer cohorts. We are the first to report increased NRF1 activity based on its differential effects on genome-wide transcription associated with luminal A and B, HER2+ and triple-negative (TN) molecular subtypes of breast cancer in women of different race/ethnicity. We observed disparate NRF1 motif-containing causal gene signatures unique to Black, White, Asian, and Hispanic women for luminal A breast cancer. Further gene order searches showed molecular heterogeneity of each subtype of breast cancer. Six different gene order sequences involving CDK1, HMMR, CCNB2, CCNB1, E2F1, CREB3L4, GTSE1, and LMNB1 with almost equal weight predicted the probability of luminal A breast cancer in whites. Three different gene order sequences consisting of CCNB1 and GTSE1, and CCNB1, LMNB1, CDK1 or CASP3 predicted almost 100% probability of luminal B breast cancer in whites; CCNB1 and LMNB1 or GTSE predicted 100% HER2+ breast cancer in whites. GTSE1 and TUBA1C combined together predicted 100% probability of developing TNBC in whites; NRF1, TUBA1B and BAX with EFNA4, and NRF1 and BTRC predicated 100% TNBC in blacks. High expressor NRF1 TN breast tumors showed unfavorable prognosis with a high risk of breast cancer death in white women. Our findings showed how sensitivity to high NRF1 transcriptional activity coupled with its target gene signatures contribute to racial differences in luminal A and TN breast cancer subtypes. This knowledge may be useful in personalized intervention to prevent and treat this clinically challenging problem.

Novel molecular targets and promising targeted therapies have reshaped diagnostics in patients with advanced non-small cell lung cancer (NSCLC). Despite this progress, the implementation of molecular screening to identify predictive biomarkers in Indian clinical and pathology settings has been challenging due to operational and logistical constraints. This consensus guideline brings together medical oncologists, molecular pathologists and pathologists from India to provide a quick and competent reference for biomarker testing in NSCLC. The guideline summarizes the importance of targetable mutations in NSCLC such as epidermal growth factor receptor (EGFR), rearrangements in anaplastic lymphoma kinase and receptor tyrosine kinase encoded by ROS-1 gene, overexpression of programmed cell death ligand-1 and resistant EGFR mutations. It reaffirms recommendations from international working groups, discusses vulnerable pre-analytical procedures and provides a balanced review on the pros and cons of different diagnostic tests (immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing and next-generation sequencing). The document also provides an algorithm to aid diagnostic decision-making and a checklist to assess the quality of testing laboratories that will help the medical oncologists make an informed choice. Overall, these recommendations are based on evidence and clinical experience and will aid policymakers, oncologists, health care practitioners and pathologists who strive to implement molecular strategies and make informed decisions for improved care in NSCLC in India.Funding: AstraZeneca Pharma India Limited.

A substantial (40‑60%) proportion of patients with non‑small cell lung carcinoma (NSCLC) have epidermal growth factor receptor (EGFR) mutations, a crucial therapeutic target in NSCLC. Treatment strategies for patients with advanced‑stage NSCLC have markedly changed, from the empirical use of cytotoxic agents to targeted regimens. EGFR tyrosine kinase inhibitors (TKIs), the first‑line therapy for advanced NSCLC, are reported to be the most effective. Although progression‑free survival (PFS) and objective response rates have long been used as endpoints, meeting these endpoints may not necessarily coincide with an increase in overall survival (OS) among patients with advanced lung cancer. Recently, the FLAURA study with the third‑generation, irreversible, oral EGFR‑TKI, osimertinib, demonstrated an extended median OS by 6.8 months compared with standard EGFR‑TKIs, with a 20% reduction in the risk of mortality [osimertinib, 38.6; EGFR‑TKIs, 31.8; hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.641‑0.997; P=0.046]; this was in addition to meeting the primary endpoint of clinically and statistically significant PFS. Osimertinib was also shown to lead to a statistically significant reduction in the risk of central nervous system disease progression (HR, 0.48; 95% CI, 0.26‑0.86; P=0.014). Notably, 28% of patients remained on osimertinib treatment for 3 years, considerably longer than those in the comparator group (9%). The duration of first subsequent treatment with osimertinib was 25.5 months compared with 13.7 months with standard EGFR‑TKIs (HR, 0.478; 95% CI, 0.393‑0.581; P

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and feared side effects in cancer patients undergoing chemotherapy. Scientific evidence proves its detrimental impact on a patient's quality of life (QoL), treatment compliance, and overall healthcare cost. Despite the CINV-management landscape witnessing a radical shift with the introduction of novel, receptor-targeting antiemetic agents, this side effect remains a chink in the armor of a treating oncologist. Though global guidelines acknowledge patient-specific risk factors and chemotherapeutic agent emetogenic potential in CINV control, a "one-fit-for-all" approach cannot be followed across all geographies. Hence, in a pioneering attempt, India-based oncologists conveyed easily implementable, region-specific, consensus-based statements on CINV prevention and management. These statements resulted from integrating the analysis of scientific evidence and guidelines on CINV by the experts, with their clinical experience. The statements will strengthen decision-making abilities of Indian oncologists/clinicians and help in achieving consistency in CINV prevention and management in the country. Furthermore, this document shall lay the foundation for developing robust Indian guidelines for CINV prevention and control.

Background: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. Methods: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups – Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions. Answers of the two groups were analyzed to see the prevailing patterns of EGFR testing and differences between the two groups if any. Results: Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR mutations in patients with adenocarcinoma histology and 40% (44/111) recommended EGFR testing in squamous cell histology. The average time duration to get EGFR test results was 10 days in Group 1 centers versus 18 days in Group 2 centers. Ninety-six percent (106/111) of the medical oncologists from Group 1 centers requested for factoring additional sample for biomarker testing compared to 69% (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of medical oncologists in Group 1 centers would prefer to wait for the test results before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine-kinase inhibitors were used in only approximately 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy was initiated while waiting for test results, 50% (56/111) of medical oncologists would prefer to complete 4–6 cycles before switching to targeted therapy. At the time of progression, rebiopsy was possible in approximately 25% of the patients. Conclusions: Turnaround time for molecular testing should improve so that eligible patients can benefit from targeted therapies in the first line. There is a need to increase the awareness among pulmonologists, oncologists, and interventional radiologists regarding the importance of adequate samples required for molecular tests.

In India, the annual incidence rates for colon cancer are 4.4 (males) and 3.9 (females) per 100,000. A common guideline for the management of metastatic colorectal cancer (mCRC) in the Indian subcontinent is lacking. Four virtual advisory board meetings consisting of a panel of 31 experts were conducted to discuss and arrive at a consensus on the treatment patterns and clinical evidence on the management of mCRC in Indian patients. The consensus covered the entirety of treatment patterns suited for the Indian subcontinent and its alignment with Pan-Asian adapted European Society for Medical Oncology guidelines. Recommendations were provided for choosing the first- and second-line agents for treatment. Types of, recommendations for, and management using salvage therapy and immunotherapy as well as management of adverse effects were discussed. Thus, the mCRC consensus is expected to serve as effective and readily available guidance for practicing oncologists across India.

Context: Secondary acute myeloid leukemia (sAML) may arise from a previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome, chronic myeloproliferative neoplasm, or as a complication in patients receiving chemotherapy or radiotherapy for a primary malignancy, including hematological and non-hematological/solid malignancies (therapy-related AML [t-AML]). Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. It is associated with specific clinical features with a uniformly poor prognosis. Objective: To study patients of t-AML with respect to clinical presentation, laboratory parameters (including flow cytometry immunophenotyping), cytogenetic and molecular studies, and clinical outcome. Design: This study was a retrospective analysis of patients of t-AML from January 2011 to December 2019. Patients: The patients underwent a detailed hematological work up: peripheral blood smear, bone marrow examination along with flow cytometric immunophenotyping, and karyotyping and molecular studies (NPM1, FLT3ITD/TKD, BCR/ABL, PML/RARA, INV16, AML-ETO). Outcomes of the patients were also reviewed. Results: A total of 20 cases of therapy-related AML were diagnosed in patients treated for various malignancies of the breast (9 cases), prostate (3 cases), and pancreas (2 cases), as well as lymphomas (NHL: 4 cases and HL: 2 cases). There were 7 males and 13 females (M:F: 1:1.85) with a median age of 63 years (range 35–82 years). Median latency period to t-AML was 3.5 years (range 0.5–11.0 years). Median haemoglobin was 72.5 g/L (61–151 g/L), WBC count 3.7× 109/L (1.02–169.1×109/L), platelet count 40 × 109/L (12–257 ×109/L, peripheral blood and bone marrow blast percentage 48% (5-98%) and 76% (20–98%), respectively. AML with monocytic differentiation was the most common morphological and flow cytometric subtype (50% cases). Complex karyotype was seen in 50% cases. Molecular studies for NPM, FLT3ITD/TKD, PML/RARA, AML-ETO, and INV16 showed 8 cases with NPM1 positivity and 4 case with FLT3ITD positivity. Only 4 patients (20%) achieved complete remission but relapsed within 1 year of duration. Ten patients succumbed to their disease, the majority within 1 year of t-AML diagnosis. Conclusion: The study highlights the development of therapy-related AML following chemotherapy and/or radiotherapy as an important therapy-related complication. The latency period and clinical manifestations may differ depending on the type of cytotoxic drug, cumulative dose, and dose intensity. A close hematological follow-up should always be done for an accurate and timely diagnosis.

Aim: A retrospective survival benefit analysis of APCEDEN®, APAC BIOTECH Pvt Ltd 69, Jacranda Marg, DLF PHASE II, Gurugram, Haryana, India, an autologous dendritic cell-based product for management of refractory solid malignancies, was performed in comparison with a control group. Methods: Subjects (retrospective data) whose survival data, geographical region, age, gender, ECOG performance status and stage of disease that could be matched with the treatment group were considered for analysis. Results: The analysis suggests a significant survival benefit of 199 days for the APCEDEN therapy treatment group when compared with the control group (356 vs 157 days). The event-free survival time of APCEDEN therapy was 439 days in patients who demonstrated an objective response at first evaluation as per immune-related response criteria. Conclusion: APCEDEN demonstrated highly convincing survival benefits when compared with the control group.

Background: Hematopoietic progenitor stem cell transplantation (HPSCT) is used as a standard treatment option to improve outcome in hematological and nonhematological disorders. It is important for new HPSCT program to look at its patient outcome data and compare it with the published data to evaluate the efficacy of program. Aims: The aim was to compile and collate the patient outcome data of HPSCT and compare with published reports. Materials and Methods: Patient demographics, indications, stem cell harvest by apheresis, dose collected, infusion, engraftment, and follow-up data were collected from hospital information system from 2010 to 2013 in a tertiary care hospital. HPSCs were mobilized with granulocyte colony-stimulating factor, and harvests were done on the 5th day. Engraftment was decided for neutrophil when counts were 0.5 × 109/L and for platelets when counts were 20 × 109/L on two consecutive days without any transfusion support. Results: There were 133 harvests for 95 patients with various disorders; multiple myeloma was most common in autologous and acute lymphoblastic leukemia in allogeneic group. One hundred harvests were done for autologous and 33 for allogeneic HPSCT. In autologous group, of 66 patients, 60 (90.9%) received stem cell infusion at median dose of 4.63 × 106 CD34+ cells/kg. Similarly, in allogeneic group, of 29 patients, 27 (93.10%) received infusion at median dose of 5.8 × 106 CD34+ cells/kg. 58 (96.9%) patients and 25 (92.6%) engrafted in autologous and allogeneic group, respectively. The median time for neutrophils engraftment was 11 days in autologous group and 12 days in allogeneic group. The median time for platelet engraftment was 11.5 days in autologous group and 13 days in allogeneic group. The 100-day survival rate was 95% n = 57) in autologous group and 77.8% n = 21) in allogeneic group. Conclusion: This data analysis shows reasonably good results of HPSCTs with majority of patients surviving at 100-day follow-up.

Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2) every 3 weeks was effective and well tolerated and showed similar tolerability compared with nab-paclitaxel 260 mg/m(2) every 3 weeks. Statistically, significant differences were not observed in the PICN and nab-paclitaxel treatment arms for radiologist-assessed ORR or median PFS. The novel paclitaxel formulation, PICN, offers apart from efficacy, potential safety advantage of decreased use of corticosteroid pretreatment and the absence of the risk of transmission of blood product-borne disease.

Rationale Prostate cancer along with colorectal and lung cancers accounts for 42% of cancer cases in men globally. It is the first cancer indication for which the use of active immunotherapy, Sipuleucel-T (Provenge) was granted by the FDA in 2010. This study presents a case of prostate carcinoma and the tumour remission observed after administration of a personalised Dendritic cell vaccine (APCEDEN). Patient concerns A 58 years old Caucasian male diagnosed with prostate carcinoma with GLEASON score 8. The patient had previously been diagnosed with Renal Cell Carcinoma (RCC) in 1996 and had undergone nephrectomy of the right kidney. PET CT scan revealed multiple intensely PSMA avid lesions noted in both lobes of the prostate gland with SUVmax -28.3 and the prostate gland measuring 3.2 × 3.2 cm displaying maximum dimensions. Diagnosis FNAC followed by PETCT confirmed CA Prostate and further supported by increased serum PSA level. Interventions The patient underwent personalised Dendritic Cell Immunotherapy APCEDEN regimen of six doses biweekly, in a time frame of 3 months were given both via intravenous and intradermal route. Six months post completion of APCEDEN, the patient was administered 6 booster shots for 6 months. Outcomes Progressive remission of carcinoma was observed along with reduction in PSA and Testosterone levels. PET CT showed decline in PSMA avidity by 50% with SUVmax -14.0 and normal size and shape of prostate gland. Lessons Prostate carcinoma is the second most common cancer in men with majority of them exhibiting locally advanced disease. Apparently 20% to 30% of them are categorized as relapsed cases after various therapeutic interventions. Modulating immune system is an emerging therapy termed as Immunotherapy and potentiates the killing cancer cells via immune activation. Interestingly, prostate cancer is slow growing and it provides the scope and time to mount an anti-tumor response which makes it an attractive target for immunotherapy. This case study demonstrates the efficacy of APCEDEN Immunotherapy regimen resulting in a significant disease remission benefiting the patient.

Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Background Refractory cancers pose formidable management challenges. We hypothesized that such malignancies have unexplored vulnerabilities that can be identified using Encyclopedic Tumor Analysis (ETA) and effectively targeted using conventional agents in a label- and organ-agnostic manner to yield treatment benefit. The pan-cancer RESILIENT trial addressed patients with advanced refractory malignancies who were treated with ETA guided treatments regimens without any restrictive eligibility criteria. Methods Molecular Profiling (MP) of patients’ fresh tumor tissue interrogated gene alterations and differentially regulated metabolic pathways to identify molecular targets of approved anticancer agents in a label-agnostic manner. Immunohistochemistry (IHC) identified hormone receptors (HR) that could be targeted with endocrine agents. Chemoresistance and response (CRR) profiling of viable tumor derived cells (TDCs) identified functional vulnerabilities of the tumor against a panel of systemic anticancer agents. Synergistic integration of MP, IHC and CRR datasets (i.e., ETA) generated patient-specific drug priority lists with projected efficacy and safety. Patients who received such ETA-guided treatments were evaluated by PET-CT scans to determine treatment response as well as Objective Response Rate (ORR), Disease Control Rate (DCR) and Progression Free Survival (PFS). Results Among the 200 patients who were screened, 110 patients received ETA-guided treatments and were evaluable for response per protocol. PR was observed in 47 patients (ORR = 42.7%) and 99 patients continued to exhibit PR or SD at study termination (DCR = 90%). Median PFS was 125 days. Median PFS rate at 90 days was 94.0%. No significant therapy related adverse events (AEs) were noted – there were no grade IV AEs or treatment related deaths. Most patients reported stable to improved Quality of Life (QoL) in terms of disease-related symptoms and functional status. Conclusions ETA-guided treatments offer meaningful survival benefits and outperformed available alternatives including checkpoint inhibitors in this heavily pretreated pan-cancer population. Legal entity responsible for the study The authors. Funding Datar Cancer Genetics Limited. Disclosure D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Ghaisas: Full / Part-time employment: Datar Cancer Genetics Limited. R. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. H. Singh: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. S. Apurwa: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Shareholder / Stockholder / Stock options, Licensing / Royalties, Officer / Board of Directors: Datar Cancer Genetics Limited. All other authors have declared no conflicts of interest.

DC Doval,1 K Prabhash,2 S Patil,3 H Chaturvedi,4 C Goswami,5 AK Vaid,6 S Desai,2 S Dutt,7 VH Veldore,8 N Jambhekar,2 A Mehta,1 D Hazarika,8 S Azam,1 S Gawande,9 S Gupta10 1Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 2Tata Memorial Hospital, Mumbai, 3Bangalore Institute of Oncology, HCG Group, Bengaluru, 4Max Super Speciality Hospital, New Delhi, 5B. P. Poddar Hospital, Kolkata, 6Medanta The Medicity, Gurgaon, 7Oncquest Laboratories Ltd., New Delhi, 8Triesta Reference Laboratory, HCG Group, Bengaluru, 9Pfizer India Ltd., Mumbai, 10Catalyst Clinical Services Pvt. Ltd., New Delhi, India Background: Mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a common feature observed in lung adenocarcinoma. A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the intracellular domain of anaplastic lymphoma kinase (ALK), named EML4-ALK, has been identified in a subset of non-small-cell lung cancer (NSCLC) tumors. The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics.Patients and methods: Patients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EGFR mutational status, were considered for this study. ALK gene rearrangement was detected by fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement Probe Kit. ALK mutation was tested in samples that were negative for EGFR mutation.Results: A total of 500 NSCLC adenocarcinoma patients were enrolled across six centers. There were 337 (67.4%) men and 163 (32.6%) women with a median age of 58 years. One hundred and sixty-four (32.8%) blocks were positive for EGFR mutations, whereas 336 (67.2%) were EGFR wild-type. Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative. The overall incidence of EML4-ALK fusion gene was 3% (15/500).Conclusion: The incidence of EGFR mutations (33%) in this Indian population is close to the reported incidence in Asian patients. EML4-ALK gene fusions are present in lung adenocarcinomas from Indian patients, and the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is similar to what has been observed in other Western and Asian populations. The mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of biomarker testing for tumors harboring ALK rearrangements in order to identify patients that can benefit from newer targeted therapies. Keywords: NSCLC, Crizotinib, Vysis ALK Break Apart Rearrangement Probe Kit

Background aims A phase II clinical trial of an autologous dendritic cell (DC) formulation for the management of refractory solid malignant tumors was conducted across six sites in India with an objective to study safety and efficacy. Methods A total of 51 patients with refractory cancer (either sex) with life expectancy ≥3 months, Eastern Cooperative Oncology Group score ≤2, available tumor tissue and adequate organ and bone marrow function were recruited. Monocytes obtained by leukapheresis, differentiated into DCs by cytokines and primed with autologous tumor lysate (fresh tissue biopsy or paraffin block). On the 8th day, mature DCs were analyzed for expression of CD40, CD80, CD83, CD86, DC205 and DC209. The treatment regime consisted of six doses (intravenous) over 14 weeks with 2 post-treatment follow-up visits, 6 weeks apart. Safety was assessed at all visits and responses were evaluated on days 58, 100 and 184 or at end of the study. Results A total of 38 patients were evaluated for safety and efficacy. One adverse event classified as possibly related was an episode of rigors or chills with mild pyrexia during one infusion. Objective response rate by Response Evaluation Criteria In Solid Tumors was 28.9% (11/38) and immune-related response criteria was 42.1% (16/38); 90% confidence interval for objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation Criteria In Solid Tumors and immune-related response criteria, respectively. The median time to treatment progression was >9 weeks. Median overall survival was 397 days. An increase in the expression of interferon-γ was not significant. Conclusions Therapy was safe. The responses, time to treatment progression and survival are encouraging for patients with aggressive refractory disease.

Title: "A prospective observational study of clinico-pathological features, prognostic factors and treatment response to primary therapy in Multiple Myeloma at a tertiary care centre" Background: Multiple myeloma (MM) is characterised by the neoplastic proliferation of plasma cells leading to excess monoclonal immunoglobulins. The incidence of multiple myeloma in India ranges from 1.2 to 1.8 per 100,000. There is paucity of cytogenetic data from this part of subcontinent. The aim of our study is to report various clinicopathological features, evaluate biological markers of prognostication including cytogenetic variables and assess treatment response after standard primary therapy. Methods and Materials: The study was carried out at a tertiary care center in Northern India. After final diagnosis of multiple myeloma was established, each patient was risk stratified via FISH cytogenetic analysis as per the revised ISS. Definitive management plan was individualised, including assessment for high dose therapy with peripheral blood stem cell support. Treatment response were recorded as per standard IMWG response criteria. Significant toxicities associated with treatment were also recorded. Results: Eighty consecutive patients with newly diagnosed multiple myeloma were enrolled prospectively from April 2017 to November 2018. The median age at diagnosis was 63 years, and number of males & females were equal. The most common presenting symptom was back pain (67.8 % patients) and most frequent clinical sign was pallor (86.4 %). All four CRAB features were documented only in 16.9% patients. M-Band was present in 96.6% patients and on SFLC assay 59.3% and 40.7% were kappa and lambda light chain restricted respectively. Most common heavy chain abnormality detected was IgG. Seventy percent patients had lytic lesions on imaging while only 3% suffered skeletal related events. Cytogenetic evaluation by interphase FISH was carried out in all patients upfront. No chromosomal abnormality was documented in 61.25 % while among those with chromosomal abnormalities, most commonly detected was del13q14.3 (23.75 %). Overall, 66.6% patients were stratified as standard risk, 28.1% as intermediate risk and only 3 (5.3%) patients were categorised as high risk. Most common induction regimen was VRD. Overall response rate was 94.9 % and VGPR or better responses were observed in 77.9% patients. Most common adverse effect of therapy was peripheral neuropathy of all grades. Of the 77 patients who completed primary therapy, 21.4% patients underwent high dose therapy with peripheral blood stem cell support while 67.7% patients were started on maintenance therapy. Four (5.1 %) non-responder was started on 2nd line treatment. On univariate analysis, higher deeper responses (VGPR or better) were observed in patients with IgA & IgG related myeloma and better overall response rates were seen in IgG related myeloma. Those with kappa light chain myeloma had 5.67 times higher likelihood of achieving response as compared to lambda light chain myeloma. Also, patients with kappa light chain myeloma achieved higher VGPRs as compared to lambda light chain myeloma. There was 17 times high risk of non-response in the presence of local bony tenderness. None of the findings were found to be significant on multivariate analysis. Conclusions: Use of interphase FISH to identify various cytogenetic markers help in stratification & staging of the disease which in turn act as a marker for prognostication. They should be a part of standard care in multiple myeloma. In majority we could administer treatment in accordance to standard practice guidelines and response rates were similar to those reported my seminal studies. Our study in a longer follow up will yield some useful information which will help in the better care of the patients. Disclosures No relevant conflicts of interest to declare.

Background: Diffuse Large B cell Lymphoma (DLBCL) accounts for nearly 25% of all Non-Hodgkin's lymphoma (NHL) in the developed world, making it the most common lymphoma. With the diversities in clinical presentation, morphology, molecular and genetic alterations, DLBCL represents a heterogeneous group rather than a single disease entity. Based on the cell-of-origin (COO) concept, gene expression profiling (GEP) has identified two major subtypes of DLBCL with differing prognoses. We aim to study the trends in the clinico-pathological features, prognostic factors and treatment outcomes following standard therapy between the molecular subtypes. Methods: A prospective study with 243 consecutively diagnosed cases of DLBCL between September 2009 and April 2017 were included. The clinico-pathological features, IPI score, extranodal involvement and stage of disease were recorded using a predesigned proforma. All patients received Rituximab based treatment which was modified according to their tolerability. Molecular subtyping to GCB and ABC subtype was performed using immunohistochemistry.Primary objective was to assess the clinico-pathological features, prognostic factors and differences between the molecular subtypes in Indian population. Secondary objective was to study the overall progression free survival (PFS). Results: Out of 243 patients enrolled in the study, 47% (n=129) were > 60 years, the median age being 55 years. Majority were males (63%). Fever (28%), pain abdomen (11%), weight loss (30%) and painless neck swelling (26%) were the most common symptoms. Nodal presentation was more common than extranodal [56.4% (n=137) versus 43.7% (n=106) respectively]; stomach (12.2%) being the most common extranodal site. 22.6%(n=55) high intermediate and 38.3% (n=93) with high IPI score. Bone marrow involvement was detected in 23% population (n=56). 51% (n=124) were diagnosed as stage IV, 24.3% (n=59) stage III, 16% (n=39) stage II and 8.6% (n=21) in stage I. Molecular subtyping was performed in 198 patients (81.4%) with GCB subtype seen in 45.5% (n=90) and ABC in 54.5% (n=108). 62.6% achieved complete metabolic response (CMR) and 18.9% (n=39) had disease progression. ABC subtype had more extranodal presentation [(54.6%, n=59 v/s 35.6%, n=32); p=0.007]. More number of disease progressions [17.8%; n=18 v/s 10.1%, n=9] and deaths [11.9%; n=12 v/s 3.4%, n=3]; p=0.046 were recorded in ABC Subtype. High IPI Score was seen in ABC subtype [45.6%, n=47 v/s 28.1% [n=25], p=0.063. Median survival time of patients was 81 months + SE 1.705 [CI 72.26-78.95]. There was a significant difference in the median PFS among those whose did not progress versus those who did [87.22 months v/s 72.66 months]. ABC subtype, high LDH Levels > 618 and patients with higher stage at presentation had disease progression. In this study, using both univariate and multivariate cox regression model, no risk factor was found to be associated with survival. Conclusions: R-CHOP remains the standard of care for patients with DLBCL. However, literature reports a cure rate of only 60% with standard immuno-chemotherapy with 40% eventually dying of the relapsed disease. DLBCL can no longer be considered and treated as one disease. It is imperative to identify those molecular and prognostic markers that would identify subset of patients who would benefit from a more aggressive course. Disclosures No relevant conflicts of interest to declare.

Background Though mTOR inhibition is considered an attractive strategy for cancer management, anti-mTOR monotherapies have not shown meaningful benefits. We hypothesized that an Encyclopedic Tumor Analysis (ETA) can identify vulnerabilities in the tumor in addition to mTOR activation. We further hypothesized that tandem synergistic targeting of these vulnerabilities using combination of mTOR inhibitors and other systemic anticancer agents in a label- and organ-agnostic manner can improve outcomes in refractory solid organ cancers as compared to mTOR inhibition monotherapy alone. Methods Molecular Profiling (MP) of patients’ fresh tumor tissue interrogated gene alterations and differentially regulated metabolic pathways to identify druggable molecular targets in a label-agnostic manner. Immunohistochemistry (IHC) identified targetable hormone receptors (HR). Chemoresistance and response (CRR) profiling of viable tumor derived cells (TDCs) identified vulnerabilities of the tumor against a panel of systemic anticancer agents. Molecular indications linked to PIK3CA, mTOR, PTEN or TP53 genes were used for selection of mTOR inhibitors. Synergistic integration of MP, IHC and CRR datasets (i.e., ETA) generated patient-specific drug priority lists with projected efficacy and safety. Patients who received such ETA-guided treatments were evaluated by PET-CT scan to determine treatment response. Results Among 41 patients who received combination treatments, 23 patients showed PR (ORR = 56.1%), 16 showed SD (DCR = 95.1%) and progression was observed in 2 patients. One patient who received monotherapy progressed at 27 days. Median PFS was 110 days (range 27 to 592). In the SHIVA trial where patients with mTOR activation (n = 46) received monotherapy with mTOR inhibitor, median PFS of 72 days (range 57 to 100) was reported. No significant therapy–related adverse events were reported in any patient. Most patients reported stable to improved Quality of Life (QoL). Conclusions ETA-guided combination regimens with mTOR inhibitors offer a viable and efficient strategy in advanced refractory malignancies and outperform mTOR inhibitor monotherapy. Legal entity responsible for the study The authors. Funding Datar Cancer Genetics Limited. Disclosure D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Ghaisas: Full / Part-time employment: Datar Cancer Genetics Limited. R. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. H. Singh: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. S. Apurwa: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Datar Cancer Genetics Limited. All other authors have declared no conflicts of interest.

We present a rare case of acute promyelocytic leukemia (APL) presenting as pulmonary thromboembolism being misdiagnosed as community.acquired pneumonia. Thrombotic phenomenon in APL are poorly understood and grossly underreported. In our case, following no response to standard antibiotic treatment, the patient was further investigated and detected to have an acute pulmonary thromboembolism following right lower limb deep vein thrombosis (DVT). Though, complete blood picture revealed only mild hyperleukocytosis, bone marrow biopsy and aspiration revealed 60% blasts and a positive t (15,17)(q22,12) and PML retinoic acid receptor alpha (RARA) fusion protein on molecular cytogenetics. He was diagnosed as APL and received treatment with all.transretinoic acid (ATRA) and arsenic trioxide (ATO) and therapeutic anticoagulation

Sezary syndrome (SS) is more aggressive leukemic variant of cutaneous T-cell lymphoma in which a significant number of circulating malignant (Sezary) cells are observed in peripheral blood. Although single-agent or combination chemotherapy regimens have produced moderately high response rates in patients with advanced-stage SS, these responses are invariably not durable. Extracorporeal photopheresis (ECP) is recommended as an immunomodulator treatment, offering better life quality for patient. We would like to present the first SS case treated successfully with low-dose methotrexate and ECP in India. A 50-year-old male presented with rash and severe pruritus all over the body for 2 years. He had received various treatment regimens but without any symptomatic improvement. He underwent detailed examination and diagnosis of SS was established. Peripheral smear revealed total leukocyte count of 14900/μ l with 55% cells reported as Sezary cells. Contrast-enhanced computerized tomography revealed few insignificant (

PurposeTAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor–copositive metastatic breast cancer (MBC).Patients and MethodsPostmenopausal women with HER2/hormone receptor–copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population.ResultsOverall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor–positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure.ConclusionTrastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor–copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.

Metastasis to the breast from an extra-mammary primary is a rare phenomenon; metastasis from gastric carcinoma to the breast is extremely so. We report a case who initially presented as mucin-secreting and signet-ring cell tumor of the ovary, and after an interval of 8 months with breast and chest wall metastatic nodules. The covert gastric primary eluded the oncologists at both presentations.

We report a rare case of a 35-year-old man who presented with a 1-week history of retrosternal chest pain of moderate intensity. A positron emission tomography CT (PET-CT) showed a large fluorodeoxy-glucose (FDG)-avid heterogeneously enhancing necrotic mass in the anterosuperior mediastinum with a focal FDG-avid thrombosis of the superior vena cava (SVC) suggestive of tumour thrombus and vascular invasion. α-Fetoprotein levels were raised (5690 IU/L). Image guided biopsy of the mediastinal mass was suggestive of non-seminomatous germ cell tumour (NSGCT). The patient received four cycles of BEP (bleomycin, etoposide and cisplatin) along with therapeutic anticoagulation with low-molecular-weight heparin. Follow-up whole body PET-CT revealed complete resolution of mediastinal mass and SVC tumour thrombosis. The documentation of FDG-PET-avid tumour thrombus resolving with chemotherapy supports the concept of circulating tumour cells being important not only in common solid tumours such as breast and colon cancer but also in relatively less common tumours such as NSGCT. The detection of circulating tumour cells could help deploy aggressive regimens upfront.

E X E C U T I V E S U M M A R YAccording to the 2008 revision of the World Health Organization (WHO) classification of myeloid malignancies, philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin) led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years. The MPN-Working Group (MPN-WG), a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India. This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India.

e13111 Background: Lung cancer diagnosis now involves routine use of biomarker testing to identify the driver mutations. We conducted a survey of 111 medical oncologists across India to understand the current pattern of EGFR mutation testing at their respective centres. Methods: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial labs. Answers of the two groups were analysed to see the prevailing patterns of EGFR mutation testing and differences between the groups if any. Results: In India, 95% of medical oncologists recommend testing for EGFR mutations in patients with adenocarcinoma histology. 40% would also recommend testing in squamous histology. 80% of medical oncologists request for biomarker testing at the time of primary biopsy. From the time of biopsy, the average time duration to get EGFR test results is 18 days. In centres with in-house testing (Group 1), results are available in 10 days. 96% of the medical oncologists from Group 1 centres request for factoring additional sample for biomarker testing compared to only 69% from Group 2. 69% of medical oncologists in Group 1 centres would prefer to wait for the test results before initiating treatment compared to 46% in Group 2. EGFR TKIs are used in 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy is initiated while waiting for test results, 50% of medical oncologists prefer completing 4-6 cycles before switching to targeted therapy. At the time of progression, rebiopsy is possible in 25% of the patients. Rapid disease progression and poor PS were the two most common reasons given for the low rebiopsy rates. Conclusions: Application of molecular testing is ‎improving. Yield can be improved by training of multidisciplinary team involved in tumor biopsy. There is scope and need to reduce the turnaround time. This will reduce the current scenario of commencing chemotherapy while waiting for test results. Increasing application of liquid biopsy will help in initial diagnosis as well as at relapse, especially for patients with poor PS or difficult access to tumor site.

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Primary renal osteogenic sarcoma is a rare malignancy. Renal metastases from skeletal osteogenic sarcoma occur more frequently. Primary renal osteogenic sarcoma has an equal sex distribution and is a tumor of middle-aged and elderly individuals. We report a 60-year-old hypertensive woman who presented with left flank pain and who was found to have primary renal osteogenic sarcoma. We describe the clinical course of this unusual malignancy, with a short review of the literature.

A 50-year-old man was diagnosed as classical Hodgkin's lymphoma stage III B. He had been a reformed smoker and has had a coronary artery disease as his comorbidity. He was started on adriamycin, bleomycin, vinblastine, dacarbazine (ABVD)-based chemotherapy. An interim disease evaluation was suggestive of metabolic complete response after four cycles of ABVD. After completion of his sixth cycle, he presented with low-grade fever, dry cough, generalised malaise and increasing dyspnoea on exertion. FDG (18 fluoro-deoxyglucose) positron emission tomography (PET)-CT revealed intensely FDG avid diffuse activity in mid and lower zone both lung fields. He was started on intravenous steroids along with broad spectrum antibiotic and antifungal cover. Clinical, radiological and laboratory assays did not reveal any infective pathology. He was diagnosed as bleomycin-induced pulmonary toxicity (BIP). Despite best supportive care, his pulmonary functions deteriorated and he developed cardiac arrhythmias. He finally succumbed to the irreversible chemotherapy toxicity of a curable malignancy.

Introduction Multiple myeloma (MM) is a malignancy involving terminally differentiated plasma cells. It is characterized by a complex pattern of extensive genomic aberrations involving many chromosomes and it constitutes about 1% of all malignancies. Its exact incidence in India is not known. Based on data available from 6 population-based cancer registries in India (covering 0.3% of the population) its incidence varies from 0.3 to 1.9 per 100 000 for men and 0.4 to 1.3 per 100 000 for women. Among various prognostic markers in MM, cytogenetic abnormality detected by conventional cytogenetic and FISH studies are major factors deciding clinical outcome. Interphase FISH studies from various parts of the world have reported variable incidence (40 - 66%) of cytogenetic abberations. However, there is insufficient published data from Indian subcontinent addressing the frequency of chromosomal aberrations using interphase FISH in MM patients. Patients and Methods Sixty eight patients clinically diagnosed with multiple myeloma were studied. The retrospective period of recruitment was from Jan 2015 to June 2016. The diagnosis of MM was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and end organ involvement. Interphase FISH analysis was performed on bone marrow samples using specific DNA probes- Del 13q14.3 (LSI D13S25) , t (4;14) ( Kreatech IgH/ FGFR3 DC-DF), t (11;14) (Zytovision directly labeled IgH/CCND1 DC-DF), t (14;16) (Kreatech IgH/ MAF DC-DF), Del 17p13.1( LSI TP53). A total of two hundred nuclei were enumerated for each FISH Panel probe and cut off for detection of deletion/ fusion signal in normal individuals was taken as 3%. An interim analysis of treatment protocols was also done. Results A total of 68 cases with MM were evaluated which included 55 males and 13 females. We report a median age of 58 years (37-86 years). Interphase FISH analysis was done in all patients. Out of sixty eight patients, 23 (33.82%) patients had one genetic abnormality. Results revealed that deletion 13q14.3 was the most frequent aberration. Out of 68 patients, 10 patients have 13q14 (14.7%) abnormality. This includes 70% males and 30% females. In addition absence of p53 at 17p13 was detected in 8/68 (11.8%) patients. Similarly 11q13 abnormality was observed in 3/68 (4.4%). IgH (14q32) aberrations were noted in 2/68 (2.94%) patients. Of which t(4;14) was detected in these patients, whereas none of them showed t(14;16). More than one chromosomal aberrations were present in 4 patients. Data for serum β2-microglobulin at the time of presentation could be evaluated in 52 patients only. Most of the patients 40(76.9%) belonged to ISS stage 3. From the available data, 4 patients with ISS stage 3 had high risk chromosomal abnormality whereas 3 patients with ISS stage 2 and none of the patient of ISS stage I disease had high risk chromosomal abnormality. A total of 40 patients received cyclophosphamide, bortezomib and dexamethasone as the primary treatment whereas 23 patients received Bortezomib, lenalidomide and dexamethasone based therapy. Post 2 cycles of cyclophosphamide based therapy showed an overall response rate (CR + VGPR) of 87.5% whereas in case of lenalidomide based therapy the overall response rate was 91%. Thirteen patients underwent autograft after durable response, out of which one had a clinical relapse within 3 months. Median survival can only be commented on further follow up. Conclusion In comparison to the west, the frequency of chromosomal aberrations are different and much less in India whereas the studies of median survival is comparable. An early age of presentation in Indian subcontinent is another issue to be addressed as we know that secondary mutations accumulate with increasing age, but a younger population presenting with same severity of disease needs exploration of additional abnormalities in India. Being a resource constraint country and non availability of molecular lab at every place, evaluation of each patient is difficult, however increasing awareness of the role of biology in the management of MM is inspiring the clinicians for detailed evaluation and close follow up of these patients. Certainly, larger trials are required to understand the biology of this disease in the country. Disclosures No relevant conflicts of interest to declare.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

Pericardial mesothelioma remains a disease with a bleak prognosis. We report the case of a patient with metastases to liver and good response to pemetrexed and carboplatin-based combination chemotherapy and consequent prolonged progression-free survival.

e19114 Background: Testing for driver mutations like EGFR has become common for the management of lung cancer. We conducted a pan India survey to ascertain the pattern of EGFR mutation testing acro...

A 47-year-old woman presented with ascites. There was history of large volume paracentesis and the drained ascitic fluid was found to be positive for malignant cells. Clinical examination revealed a soft tissue nodule over the skin of right iliac fossa and a small umbilical nodule besides presence of ascites. In addition, the patient had a breast lump of 2×2 cm in upper quadrant of right breast. Biopsy from the abdominal wall nodule revealed a malignant tumour with dense desmoplastic response. The tumour cells were pancytokeratin, CA125, WT1 positive and CDX2, CD10, villin, calretinin negative; thus immunohistochemically suggesting a primary tumor arising from ovary. Biopsy from breast lump showed malignant epithelial cells present in sheets with stromal dysplasia. Immunohistochemically tumour cells were positive for CK7. CA125, WT1, thus favouring a metastatic carcinoma to breast with possible primary arising from ovary.

7569 Background: Talactoferrin alfa (TLF), a novel immunomodulatory agent, has demonstrated anti-tumor activity in two randomized, placebo-controlled phase II studies in NSCLC, including a 100-pati...

7540 Background: Talactoferrin alfa (TLF), an immunomodulatory protein with a novel anti-cancer mechanism of action, was active preclinically and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Randomized Phase 2 studies in NSCLC were conducted with TLF as a single agent and combined with chemotherapy. The 110-patient combination therapy study, which was previously presented (ASCO 2006, #7095), met its primary endpoint with an improved BOR over chemotherapy alone. We now present results from the placebo- controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first or second line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive best supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered until disease progression, for up to three 14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with an a=0.05. Results: All patients had previously received a 1st line platinum based regimen; 26 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 55% increase (2.1 month; p [Table: see text] [Table: see text]

17141 Background: Gefitinib is an orally active EGFR-TKI (Epidermal Growth Factor Tyrosine Kinase Inhibitor) that demonstrated, clinically meaningful anti tumor activity, favorable toxicity profile in phase II trials involving patients with advanced pretreated NSCLC. The aim of this study was to assess the antitumour activity (time to disease progression) and toxicity profile of Gefitinib. Methods: Twenty five patients of NSCLC advanced were included in this study who have failed at least one chemotherapy regimen and completed at least one month Gefitinib (250 mg/day) therapy. The study included 18 male and 7 female patients with, a median age of 60 years (32–80 years) and performance status ECOG 0-I 64%. The histologically included were Adenocarcinoma 56%, Squamous Cell Carcinoma 40% and Large Cell Carcinoma 1%. 64% patients had failed to response to 1 (CT) chemotherapy regimen, 28% to 2 CT and 8% to 3 CT regimens. Results: A total of 25 patients (18 male, 7 female) were evaluated for response. 2 Complete Response (CR) and 1 Partial Response (PR) were observed with an Overall Response Rate (ORR) of 12% (CR+PR). All the three patients were with Adenocarcinoma histology. A total of 14 patients (56%) had Stable Disease (SD). This led to an Overall Disease Control Rate (CR+PR+SD) of 68% (17 patients). The Median Time to Progression (TTP) was 3.8 months using the SAS method for statistical analysis (95% CI 4.4–9.3). The number of previous chemotherapy regimens did not alter the response to therapy. All the patients were evaluated for toxicity profile assessment (25 patients). The most frequent toxicity observed was Asthenia in 52% of patients. Other toxicities were Diarrhaea 24%, Skin Disorders 32%, Anorexia 32%, Vomitings 44%. Only 1 patient had grade IV skin related toxicity. No deaths related to Gefitinib treatment were reported. Conclusion: Gefitinib shows antitumour activity in pretreated patients of advanced NSCLC. Gefitinib therapy of (250 mg/day) has a favourable toxicity profile and is well tolerated. Gefitinib is a viable therapy in NSCLC patients who have limited treatment options. No significant financial relationships to disclose.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of NHL. Different chemotherapy regimens tested in the past showed RR of appx 80% with no improvement in prognosis & OS. CHOP regimen has been the standard treatment for these patients (pts). Rituximab has improved response rates & survival in CD20 positive lymphoma pts, especially elderly (GELA trial: CR 73% vs. 63%). We retrospectively evaluated pts of DLBCL treated with R-CHOP regimen between April 2001 & June 2005. All pts had biopsy and IHC of lymph node/extranodal site, & CT scan of neck, chest, abdomen; BM biopsies; CBC, serum chemistries; 2D echocardiography/MUGA scans. All pts received Rituximab (375mg/m2) & CHOP 3 weekly for a maximum of 8 cycles. Pts who received at least 1 & 3 cycles of R-CHOP were evaluable for toxicity and response respectively. In total, 36 pts were included for analysis. The median age was 53 years, 10/36 pts (27.8%) were >60 years. 25/36 were male (69.4%). ECOG performance status: 0–1 in 30/36, and 2–4 in 6/36. 11/36 had B-symptoms, 16/36 had high LDH, 6/36 had bulky disease. Extranodal involvement was present in 19/36; 10/36 had ≥2 sites of extranodal involvement. Lymph nodal swelling was most common presentation in 24/36 (66.7%), followed by pain 10/36 (27.8%), weight loss 9/36 (25%), fever 7/36 (19.4%), skin nodules 3/36 (8.3%). Extranodal sites were: bone marrow 5/36, bone 4/36, skin 3/36, GIT 3/36, pleural effusion 2/36, lungs 2/36, other soft tissue 2/36, and parotid, nasopharynx, orbit, adrenal, testes, kidneys-1 each. Gallium scan at base line, done in 12/36, was positive in 11 pts (91%). Stage distribution was as follows: stage-I none, stage-II 10/36 (27.8%), stage-III 13/36 (36.1%), stage-IV 13/36 (36.1%). IPI scoring was-low risk 13/36 (36.1), low intermediate 9/36 (25.0%), high intermediate 13/36 (36.1) & high risk 1/36 (2.8%). A total of 199 cycles of R-CHOP were administered with a median of 6 cycles per patient. Of the 33 pts evaluable for response, 22 achieved CR (66.7%), 9 PR (27.3%), 1 each SD & PD. There were 2 treatment related mortalities. Toxicities were: grade III/IV neutropenia in 12/36 (33.3%), thrombocytopenia 4/36 (11.1%), peripheral neuropathy 2/36 (5.6%). Mild hypersensitivity to Rituximab was seen in 2/36 (5.6%) pts. Only 1 patient had cardiac toxicity in form of CHF. Our study showed response rates (94%) and toxicity profile similar to what has been reported in other studies with R-CHOP. The follow-up is too short to evaluate survival rates. Keywords: DLBCL, Rituximab, CHOP.

815 Background: Capecitabine (C) is a fluropyrimidine carbamate derivative, which is an easily administered, tumor activated and tumor selective cytotoxic agent. C has shown promising efficacy in M...