Clinicopathological features, treatment and survival outcomes of synovial sarcoma.

INTRODUCTION: Synovial sarcoma (SS) is a malignant mesenchymal tumor. It is most common among children and adults. The data on SS from India are scarce. In this study, we analyzed the clinicopathological treatment parameters and survival outcomes of SS patients. MATERIALS AND METHODS: A total of 57 histologically proven SS diagnosed from 2010 to 2016 were retrospectively analyzed. RESULTS: The median age was 23 years with a male-to-female ratio of 1.28:1. Localized disease was seen in 44 patients (77%) and 13 patients (23%) had metastasis. The primary sites of involvement such as lower limb, upper limb, thorax, and abdomen were seen in 60%, 28%, 7%, and 5% patients, respectively. Surgery was done in 39 patients and 18 patients had unresectable disease. Adjuvant chemotherapy with doxorubicin-based regimen was given in 30 patients and adjuvant radiotherapy in 21 patients. Palliative chemotherapy with anthracycline-based or gemcitabine-based regimen was used in 17 and 2 patients, respectively. The median event-free survival (EFS) was 30 months with 3 years and EFS rate was 36%; median progression-free survival (PFS) was 11.5 months and 1 year; and PFS rate was 38%. On univariate analysis, resection and performance status were significantly associated with survival. There is no impact of grade and size of the tumor on survival. In metastatic patients, the lung is the most common site. CONCLUSION: SS is the most common soft-tissue sarcoma among adults. Resectability and performance status were impacting the survival.

Effectiveness of Three Prognostic Scoring Systems in Predicting the Response and Outcome in Pediatric Chronic Myeloid Leukemia Chronic Phase on Frontline Imatinib.

INTRODUCTION: The Sokal and Hasford (Euro) scores were developed in the chemotherapy and interferon eras and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, European Treatment and Outcome Study (EUTOS) scoring system was introduced. Data on risk stratification in pediatric CML population was lacking due to its rarity (<3%). OBJECTIVE: To study the effectiveness in predicting the response and outcome with three prognostic scores in pediatric CML-chronic phase patients on front line Imatinib. Materials and Methods: We retrospectively analyzed the hospital records of newly diagnosed CML CP patients (aged ≤18 years) from 2006 to 2010 for their risk score, cytogenetic response at 18 months and event free survival (EFS) at the end of 4 years. Events include loss of hematological response, loss of cytological response, progression to accelerated/blast phase (AP/BC). All received free Imatinib under Gleevac international patient assistance program. RESULTS: Data of 106 children was analyzed with median age of 13.5 (ranged 5-18 years) and male preponderance (M:F = 1.14:1). The distribution of children was 63%, 32% and 5% in Sokal low, intermediate and high risk respectively, 50%, 43% and 5% in Hasford/Euro low, intermediate and high risk respectively, 71% and 29% in EUTOS low and high risk respectively. The overall cumulative complete hematological response at the end of 3 month was 94%, and complete cytogenetic response at 12 months was 75%. The CCyR at 18 month was seen in 90%,74% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 84% and 86% EUTOS low and high risk groups respectively. The EFS at the end of 48 months was seen in 87%,79% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 86% and 80% EUTOS low and high risk groups respectively. CONCLUSION: None of the scoring systems predicted the response and outcome effectively in children with CML CP on front line Imatinib.

Generic Imatinib in Chronic Myeloid Leukemia: Survival of the Cheapest.

INTRODUCTION: The patent expiration of imatinib mesylate (Gleevec; Novartis) on February 1, 2016, has brought the focus back on generic versions of the drug, and an opportunity to provide a safe and cost-effective alternative. The objective of our study was to determine the molecular and cytogenetic responses, survival endpoints (event-free survival, failure-free survival, transformation-free survival, overall survival), and safety of innovator and generic brands of imatinib. MATERIALS AND METHODS: In this retrospective analysis, data from 1812 patients with chronic myeloid leukemia treated with frontline imatinib mesylate (innovator/generic) at a single institution between 2008 and 2014 is included. Of these, 445 were excluded owing to inadequate data and follow-up, and a further 156 were excluded as they were in either the accelerated phase or blast crisis at diagnosis. Thus, data from 1067 patients who were treated with Gleevec (Novartis), and 144 patients with Veenat (NATCO) were available for analysis, and included in the study. RESULTS: There was no significant difference in event-free survival (P = .05), failure-free survival (P = .07), transformation-free survival (P = .12), or overall survival (P = .24) between the 2 groups. The frequency of reported nonhematologic adverse events and hematologic adverse events was comparable between the study groups. CONCLUSION: The findings of the present study showed comparable efficacy and safety of the generic and innovator versions of imatinib in the treatment of patients with chronic myeloid leukemia.

Treatment Challenges and Survival Analysis of Human Epidermal Growth Factor Receptor 2-positive Breast Cancer in Real World.

CONTEXT: Advent of trastuzumab has brought tremendous changes in the survival of human epidermal growth factor receptor 2 (Her2)-positive breast cancer patients. Despite the availability of the drug, it is still out of reach for many patients. There is very limited real world data regarding treatment challenges and survival analysis of these patients. AIMS AND OBJECTIVES: Primary objective is disease-free survival (DFS) and secondary objective is overall survival (OS) and toxicity profile. STATISTICS: Statistical analysis is done using GraphPad Prism 7.02. MATERIALS AND METHODS: This is a retrospective study of all patients diagnosed with Her2-positive (Her2+) nonmetastatic invasive breast cancer from January 2007 to December 2013. RESULTS: In the period of this study, 885 patients are diagnosed with carcinoma breast, of which 212 are Her2/neu positive (23.9%). Of the 212 patients, only 76 (35.8%) patients received trastuzumab along with chemotherapy. Patients receiving trastuzumab with chemotherapy have longer 5-year DFS compared to those receiving chemotherapy alone, 92% and 52.6%, respectively (P = 0.0001). Five-year OS is 90.5% and 41.7% in those patients who received chemotherapy with and without trastuzumab, respectively (P = 0.0001). Seven patients (9.45%) developed Grade II reversible diastolic dysfunction. Grade II/III peripheral neuropathy due to paclitaxel is the main adverse effect seen in 21 patients. CONCLUSION: In spite of improvement in DFS and OS with trastuzumab, the number of patient receiving targeted therapy is very low due to financial constraints which need to be addressed to bridge the gap in survival of Her2+ patients.

Clinicopathological Features and Outcomes in Primary Central Nervous System Lymphoma: A 10-year Experience.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a variant of extranodal lymphoma, accounting for 4% of primary central nervous system tumors. PCNSL was more common in immunocompetent individuals. International Extranodal Lymphoma Study Group (IELSG) scoring was used for prognostication. High-dose methotrexate regimens along with radiotherapy improved outcomes in PCNSL. AIMS: The aim of this study is to analyze the clinical and pathological features, progression-free survival (PFS), and overall survival (OS) in patients with PCNSL. MATERIALS AND METHODS: Data of patients with PCNSL between 2005 and 2016 were retrospectively analyzed. Outcome was analyzed in patients who received chemotherapy. GraphPad Prism software for Windows Version 6 was used to plot the Kaplan-Meier curves for PFS and OS. Log-rank test was used to calculate P values. P < 0.05 was considered as statistically significant. RESULTS: A total of 42 patients were available for analysis. Of these, 34 patients who received chemotherapy were evaluable for outcome parameters. The median age at presentation was 46 years (range, 10-75) with male-to-female ratio of 2.2:1. Only 2 (4.7%) patients were HIV positive. Diffuse large B-cell lymphoma (DLBCL) was the most common histology seen in 41 (97.6%) patients. Using IELSG risk scoring, scores of 8 (19%), 19 (45.2%), and 15 (35.8%) were stratified into low, intermediate, and high risk. The median PFS and OS were 11 months (range, 2-72) and 15.9 months (2.4-80.4), respectively. The median OS was 36.2 months (range, 8.8-72), 15.6 months (2-36), and 6.1 months (2.6-12.7) in low-, intermediate-, and high-risk groups, respectively, which was statistically significant (P = 0.0002). CONCLUSIONS: Immunocompetent patients with PCNSL outnumber immunocompromised patients. DLBCL was the most common histology, and IELSG risk stratification significantly predicts the outcome in PCNSL.

Impact of treatment protocol on outcome of localized Ewing's sarcoma.

BACKGROUND: The outcome of localized Ewing's sarcoma has improved with multi-disciplinary approach. Survivals of Ewing's sarcoma from the Asian countries differed between centers. METHODS: We retrospectively analyzed the records of newly diagnosed localized Ewing's sarcoma patients from 2002 to 2012. The patients were analyzed in three groups; Group 1(2002-2004) who received non-ifosfomide based regimens, Group 2(2005-2008) who received VDC/IE for 12 cycles, and Group 3(2009-2012), who received VDC/IE for 17 cycles. The groups were compared for their baseline characteristics, treatment protocol and outcome. RESULTS: Seventy three patients were included in the study. The median age of presentation was 15 years, with slight male predominance. Axial primary was seen in 62%. The median RFS of the three groups was 26.4, 31.4 and 36.8 months respectively (P = 0.0018). The median OS was 27.9, 35 and 43 months respectively (P = 0.0007). At a median follow-up of 35 months, the 3 year RFS and OS for the three treatment groups were 17%, 31%, 60% and 35%, 45% and 70% respectively. Larger tumor size, axial primary, high LDH were associated with poorer survival. Radiotherapy was associated with inferior local control and survival. CONCLUSIONS: We found that the survival of our ESFT patients improved over time with intensified multiagent chemotherapy and with lesser time to local therapy. But the results were still inferior to those reported in literature. We had majority of patients presenting in axial site and radiotherapy as the predominant mode of local control. The outcome may further improve with surgery as local control procedure.

Trends in management of acute lymphoblastic leukemia: Influence of insurance based healthcare and treatment compliance on the outcome of adolescents and adults with acute lymphoblastic leukemia.

AIM: In this study, we attempted to analyze the impact of insurance based health care system and treatment compliance on the outcome of adolescent and adults with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Patients who underwent treatment for ALL during the period 2003-2011 were enrolled into this retrospective study. Patients on supportive or palliative care only and patients with age <10 years were excluded. The hospital records and tumor registry records were studied. Patients were stratified into two groups, Group A (prior to the introduction of state health insurance [SHI], 2003-2007) and Group B (after the introduction of SHI, 2008-2011). Overall survival (OS) was calculated using Kaplan-Meier method. RESULTS: A total of 420 patients with suspected or confirmed ALL visited our center during the study period and 179 patients (87 in Group A and 92 in Group B) were considered for inclusion. The median age in years (range) was 18 (10-57) and 18 (10-58) respectively in Groups A and B with males more than females. Median OS (95% CI) was 9 (6.7-11.2) and 12 (7.3-16.7) months in the Groups A and B respectively (P = 0.265). Poor treatment compliance in both groups was high (36% in Group A and 41% in Group B, [P = 0.107]) with lower default rates in Group B (P = 0.019). Patients with good compliance in the total study population and the individual study groups had significantly better OS. CONCLUSIONS: Insurance based health care has improved outcomes in the present study but not compliance to treatment. Significantly better OS was observed in patients with good compliance.

Clinicopathological features and outcomes in advanced nonsmall cell lung cancer with tailored therapy.

CONTEXT: Lung cancer is an important cause of cancer-related deaths worldwide. There is an increasing incidence of lung cancer in never smokers and a shift of histology from squamous cell to adenocarcinoma globally in the recent past. Data on treatment outcomes with newer platinum doublets is scant from India. AIMS: To study the clinicopathological features, response rates (RRs), progression-free survival (PFS), overall survival (OS), and the 1, 2, and 3 years survival, in patients with advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Data of all patients who received chemotherapy for Stage IIIB and IV NSCLC between January 2010 and June 2014 were retrospectively analyzed. STATISTICAL ANALYSIS USED: Univariate analysis for OS was done by plotting Kaplan-Meier curves and the log-rank test was used to calculate P values. Logistic regression analysis for OS was carried out using MedCalc statistical software. RESULTS: A total of 353 patients received chemotherapy. Of these, 256 were evaluable for outcome parameters. The median age at presentation was 58 years with a male:female ratio of 2.53:1. The smoker:nonsmoker ratio was 1:1. Adenocarcinomatous histology was the most common both in smokers and nonsmokers reported in 70.8% patients. Epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocation were seen in 35% and 3% of patients, respectively. The RR, median PFS, OS, 1, 2, and 3 years survival were 80%, 8 months, 12.1 months, 51.5%, 12.7%, and 4.2%, respectively. There was no significant survival difference among the treatment regimen used but the response to I line chemotherapy impacted survival. Female gender, performance status, and nonsquamous histology were significant predictors of OS (P = 0.0443, P = 0.0003, P = 0.048, respectively). CONCLUSIONS: There was an increase in the incidence of nonsmokers. Adenocarcinoma was the most common histology in both smokers and nonsmokers. Treatment outcomes in advanced lung cancer were better compared to the past with the advent of newer platinum doublets and EGFR tyrosine kinase inhibitors. The response to first-line chemotherapy significantly impacts outcomes in advanced NSCLC.

Managing metastatic renal cell carcinoma-challenges, pitfalls, and outcomes in the real world.

INTRODUCTION: Renal cell carcinoma (RCC) is the most common cancer of the kidney accounting for 85% of renal tumors. Metastatic RCC (mRCC) had a poor prognosis and with the introduction of tyrosine-kinase inhibitors, such as sunitinib, pazopanib the outcomes improved. There is only one study reported from India on the use of sunitinib in mRCC. We present our analysis of mRCC and use of sunitinib at our institute over 5 years. MATERIALS AND METHODS: All patients with mRCC receiving sunitinib were analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: A total of 108 patients were seen during the study period. The male to female ratio was 9.8:1. The median age of patients at presentation was 58 years (range: 15-80 years). Of the 108 patients, 68.51% had metastatic disease at initial presentation. The most common sites of metastases were lung followed by bone. Of the 97 patients eligible for sunitinib, only 76 received at least one cycle of sunitinib, out of which only 48 received further cycles (range: 2-36). The median progression-free survival (PFS) and overall survival (OS) in our patients were 10.2 and 28.2 months, respectively. The most common adverse effect noticed in our population was mucositis followed by hand-foot syndrome. CONCLUSION: Sunitinib is an option for the treatment of mRCC and shows a good PFS in Indian patients. Median OS and PFS in this study are similar to other reported studies despite the presence of poor risk factors in the patient population. The pitfall in this study is significant attrition due to poor compliance to treatment and follow-up, which is a major factor in the clinic thereby compromising outcomes.

Prevalence and outcome of epidermal growth factor receptor mutations in non-squamous non-small cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation analysis has become an important part of the initial workup of non-squamous non-small cell lung cancer (NS-NSCLC) patients as it is now recognized both as a prognostic and predictive marker to therapy with EGFR tyrosine kinase inhibitors (TKI). AIM: In this retrospective study conducted at a University hospital, we evaluated the prevalence of EGFR mutations in patients with NS-NSCLC, clinico-pathological correlation and outcome to treatment with EGFR TKIs. MATERIALS AND METHODS: Case records of 147 patients of NS-NSCLC in whom EGFR mutation status was tested were screened. EGFR mutation analysis was done using DNA sequencing by real time polymerase chain reaction method from tissue and cell blocks prepared from core biopsy, fine needle aspiration cytology and pleural fluid specimens. RESULTS: EGFR mutations were seen in 30.6% of the 111 evaluable specimens, with a significantly higher rate in females (44% vs 19.6% P = 0.0072) as compared to men and non-smokers (41% vs 12% P = 0.0013) as against smokers. Most common mutations were observed in exons 19 (71%) and 21 (25%). The estimated median progression free survival for patients with and without mutations when treated with upfront TKIs was 12 months and 3 months respectively and the estimated median overall survival for patients with and without mutations was 20 and 9 months respectively. CONCLUSION: This study from India, further establishes the importance of upfront EGFR mutation testing in all NS-NSCLC patients, not only to prognosticate, but also to identify that subset of patients who could benefit from EGFR TKI therapy, early in the course of their disease.