A Comprehensive Correlation of Clinicopathologic Prognostic Factors in Malignant Adult Renal Tumors: A Single Institutional Study.

OBJECTIVE: To study the clinicopathologic prognostic parameters of malignant adult renal tumors as these have poor over-all survival (OS) and show frequent metastasis. MATERIAL AND METHODS: This was a retrospective analysis of the clinical and pathologic features of malignant renal tumors in adult patients from January 2011 to December 2020. All the tumors were studied with respect to age, clinical presentation, tumor type/subtype, histologic grade (WHO/ISUP grading system), TNM stage and presence of necrosis. Correlation of histopathologic features and survival analysis was done using Kaplan-Meier survival curves and Cox-regression analysis. RESULTS: A total of 257 cases were included in the study period including 253 renal cell tumors of which clear cell renal cell carcinoma accounted for 69.3%. The age of the patients ranged from 20 to 87 years (median-52 years). The overall survival significantly reduced with increasing histologic grade, stage, and presence of necrosis. The comparison between the histological subtypes was not statistically significant. Univariate Cox-regression analysis found significant hazard ratio with increasing age, size, histologic grade (G4 vs G1), stage, and presence of necrosis. The correlation of OS with histological subtypes was not significant. Multivariate analysis also showed increased hazard ratio with increasing age, size, grade, and stage. However, the P-value was significant only for age. CONCLUSION: Clear cell renal cell carcinoma was the commonest type of adult renal tumor. Older age at presentation, larger tumor size, presence of necrosis, and higher histologic grade and stage were associated with poor prognosis in these patients.

Trastuzumab-Related Cardiotoxicity in Adjuvant Setting: A Real-World Scenario.

Rachana Chennamaneni Trastuzumab, a humanized monoclonal antibody, significantly improves outcomes in HER 2-neu positive breast cancer. The incidence of cardiotoxicity with trastuzumab is approximately 8 to 10%. This study was designed to analyze the incidence and risk factors associated with trastuzumab-related cardiotoxicity in real-world settings. This was a single institutional retrospective analysis of the incidence of trastuzumab-related cardiotoxicity in nonmetastatic HER 2-positive, invasive breast cancer from January 2013 to December 2018. Trastuzumab-related cardiotoxicity was defined as symptomatic heart failure or asymptomatic decline in left ventricular ejection fraction (LVEF) by more than or equal to 10% or LVEF less than 50%. Risk factors analyzed were higher body mass index (≥30 kg/m 2 ), history of diabetes, hypertension, cardiac disease, left-sided radiotherapy (RT), and prior exposure to anthracyclines. Out of the 246 patients diagnosed with early stage HER 2-positive breast cancer, 117 (47.5%) received trastuzumab and constituted the study population. Trastuzumab-related cardiotoxicity was seen in a total of 16 (13.6%) patients. Eleven (9.4%) patients had an asymptomatic decline, while symptomatic LV dysfunction was seen in five (4.2%) patients. The median baseline ejection fraction was 65% (range, 56-72). The median time to development of cardiotoxicity was 18.5 weeks (range, 3-52) and the median trastuzumab cycle for cardiotoxicity was 6 (range, 2-16). Ten (62.5%) patients were rechallenged with trastuzumab following which one patient developed an asymptomatic decline in ejection fraction and one patient developed symptomatic heart failure. Cardiac-related mortality was seen in one (0.85%) patient. Left-sided RT to chest ( p = 0.012) and presence of more than or equal to two risk factors ( p = 0.01) had significant impact on incidence of cardiotoxicity. Approximately 14% developed trastuzumab-related cardiotoxicity that was slightly higher compared with that seen in clinical trials. Left-sided RT to chest and presence of two or more risk factors had significant impact on development of cardiotoxicity.

Complications during Induction Chemotherapy in Acute Promyelocytic Leukemia: An Institutional Experience.

Stalin Chowdary BalaIntroduction Acute promyelocytic leukemia (APL) has transformed from a highly fatal disease to a highly curable one. Induction deaths continue to represent one of the major impediments in modern therapy of APL. Sepsis, hemorrhage, and differentiation syndrome are the major complications during induction therapy in APL. The present study reports the incidence and prognostic factors of major complications during induction chemotherapy in patients with newly diagnosed APL. Materials and Methods The present study was a single institutional, observational, retrospective study. All cases of APL diagnosed by morphology and confirmed by RT PCR (PML RARα) were included in this study. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25. Results A total of 73 patients were analyzed. The median age at presentation was 30 years (range, 3-60 years) with a female to male ratio of 1.02:1. The most common symptom at presentation was fever (80%), followed by fatigue (56%) and gum bleeding (37%). The majority of the patients at presentation were high risk (42.4%), followed by intermediate risk (38.4%) and low risk (19.2%). Fifty-seven (78%) patients achieved complete hematological remission and 16 (22%) succumbed during induction chemotherapy. Infection was the most common cause of induction death (50%), followed by hemorrhage (37.5%) and differentiation syndrome (12.5%). On univariate analysis of prognostic factors, bcr3 variant, grade 3/4 bleeding during induction, and low levels of albumin at presentation were significant for induction mortality ( p = 0.034, 0.041, and 0.008 respectively). On multivariate analysis, only serum albumin < 3.5 g/dL was an independent predictor for induction mortality ( p = 0.043). Conclusion The majority of patients were high risk at presentation. Sepsis was the most common complication during induction and also the leading cause of induction death. Identifying induction complications at the earliest and providing aggressive supportive measures can further improve outcomes in APL.

Effect of serum albumin level on high-dose methotrexate induced toxicities in acute lymphoblastic leukemia patients.

Objectives: Methotrexate (MTX) is a key therapeutic agent for leukemias. When given in high doses, leucovorin rescue is added to reduce its toxicity. It has been postulated that low albumin levels are associated with delayed clearance and increased toxicity of MTX. Hence, this prospective cohort study was proposed to evaluate the correlation between serum albumin level and HDMTX toxicity in acute lymphocytic leukemia (ALL) patients and to compare the MTX toxicity in hypo and normoalbuminemic patients. Methods: Forty-six ALL patients of either gender aged 2-40 years receiving HDMTX for 1st time were included in the study. The serum albumin levels were measured before chemotherapy before each cycle. The patients received 24-h infusion of HDMTX on days 8, 22, 36, and 50 (four cycles). The serum concentration of MTX was measured after first cycle only. The patients were followed for toxicities that were graded according to CTCAE-V4.0. Results: There was a negligible correlation between cumulative albumin levels of all four cycles and cumulative toxic events. The median toxic events were 19 (16-23). The Spearmen correlation coefficient ρ was 0.055 (P = 0.460). No association was found between albumin level and MTX toxicity in cycle wise analysis also. In each cycle, there was no significant difference in the toxicities between the hypo and normoalbuminemic patients. Only vomiting showed significant (P < 0.05) inverse correlation with albumin levels. Hypoalbuminemic patients showed significantly (P < 0.01) higher grade of nausea compared to normoalbuminemia. Conclusion: There was negligible correlation between albumin levels and MTX toxicity despite delayed clearance supporting the safety of MTX in mildly hypoabuminemic patients.

Clinicomorphological and molecular analysis of medulloblastoma and association with survival: A single tertiary care center experience.

BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles, with specific molecular subgroups. Various clinical, pathological and molecular variables have been associated with disease outcome and therefore utilised in risk stratification of patients. OBJECTIVES: To perform molecular classification of medulloblastoma using surrogate immunohistochemistry (IHC) and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) of MB patients. RESULTS: This study included 65 medulloblastoma patients. Immunohistochemical staining, using ß-catenin YAP1 and GRB2-Associated Binding Protein 1 (GAB1) antibodies was used to classify MB cases into wingless signalling (WNT) activated, sonic hedgehog (SHH) activated, and non-WNT/non-SHH molecular subgroups. The relevant statistical analysis was done using GraphPad Prism version 9.3.0. Histological patterns included classic (40 cases, 62%), desmoplastic nodular (D/N) (14 cases, 22%), large cell/anaplastic (LC/A) (9 cases, 13%), medulloblastoma with extensive nodularity (MBEN) (1 case, 1.5%) and one special subtype, i.e., medulloblastoma with myogenic and melanotic differentiation. Molecular subgroups included WNT (4 cases, 6%), SHH (34 cases, 52%), and non-WNT/non-SHH (27 cases, 42%) subgroups. Histopathological types differed significantly according to tumor location, degree of anaplasia and molecular subgroups. Molecular subgroups differed significantly in age distribution and tumor location. The probability of survival was 78% and 68% after 1 and 2 years, respectively. Infants (<3 years of age), LC/A pattern, and TP53-mutant status among SHH subgroup conferred poor prognosis in our study. At the end of the study (at 65 months of maximum follow-up period) probability of survival was 51%. CONCLUSIONS: Immunohistochemical analysis helps in molecular classification of medulloblastoma in majority of the cases as well as helps in predicting prognosis and treatment response.

Hepatic epithelioid hemangioendothelioma-report of three cases of a puzzling tumor.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm with unpredictable clinical behavior. These lesions are frequently misdiagnosed owing to its non-specific symptomatology, ambiguous radiological features, and overlapping histomorphology. We report three cases of hepatic EHE, of which one was male and two were female patients. While all three patients presented with abdominal pain, the male patient gave an additional history of weight loss and was jaundiced. The radioimaging showed multiple nodules in the liver and two of the patients also had pulmonary metastasis. The biopsies of the liver nodules revealed a tumor composed of spindle, epithelioid, and stellate tumor cells, some with characteristic intracytoplasmic vacuolations/lumina surrounded by myxohyaline stroma. Some of these intracytoplasmic vacuoles/lumina showed erythrocytes, suggesting its vascular origin which was confirmed by CD31 and CD34 positivity. The article highlights the importance of histopathology and IHC in the precise diagnosis of EHE.

Multiple Myeloma in Young Adults: A Single Centre Real World Experience.

Multiple Myeloma accounts for 1% of all cancers. In India myeloma accounts for 1.23% of all cancers. The median age at diagnosis varies from 65 to 70 and only a small proportion of MMs are diagnosed at younger age, before 40 (approximately 2%). The present study is designed to analyse the clinical, haematological profile and outcomes in young adults with multiple myeloma. Data of all patients with age ≤ 40 years, diagnosed with multiple myeloma from 2013 to 2018 was analysed. A total of 258 patients were diagnosed with multiple myeloma between 2013 and 2018, of which 22 (8.5%) were aged ≤ 40 years. The median age was 33.5 years(range,18-40). Male to female ratio was 1.75:1. Bone pain (59%) and fatigue (45.4%) were the most common symptoms at presentation. Majority of patients were ISS stage 3(63.6%). Cytogenetic data was available only in seven patients and IgH translocation and del 13q were the most common abnormalities, seen in four and three patients respectively. Of 22 patients, 17 patients had at least one response evaluation and were evaluated for outcomes. Eleven patients (64.7%) had responses greater than VGPR. Six (41.6%) patients underwent Auto HSCT. Four patients received second line therapy and only two received further lines of therapy. At a median follow up of 18 months, 2-year EFS was 76.5% and 2-year OS was 94.1%. Patients younger than 40 years, constitute higher proportion of patients in Indian sub-continent. Renal failure was more common in young myeloma patients. Light chain myeloma was more common in young adults. Most patients were ISS stage 3 at presentation and survival seems to be better in young adults when compared to elderly patients.

Incidence of febrile neutropenia with commonly used chemotherapy regimen in localized breast cancer.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among the women. Most commonly used chemotherapy regimen is Doxorubicin and Cyclophosphamide (AC) which carries significant risk of febrile neutropenia. The aim of the study is to identify the incidence of febrile neutropenia and its effects on the delivery of chemotherapy in patients receiving following AC chemoregimen without primary prophylaxis. MATERIALS AND METHODS: We retrospectively analyzed the case records of the localized breast cancer patients who were treated with AC chemoregimen without primary prophylaxis for febrile neutropenia. RESULTS: Between 2013 and 2017, a total of 231 cases received AC chemoregimen. A total of 14 (6.1%) patients were found to have febrile neutropenia. All patients were recovered by day 19 and no deaths were observed. Except for ECOG performance status (P = 0.001) no significant association was found with age, co-morbidities, menopausal status, body surface area and stage of the cancer. There were no treatment delays or dose reductions because of febrile neutropenia. CONCLUSION: The incidence of FN with AC chemotherapy in breast cancer patients is relatively less in the present study. Routine primary prophylaxis is not recommended as this chemotherapy falls in to low risk category for FN but can be considered for patients with ECOG PS > 1. If the diagnosis of febrile neutropenia and institution of appropriate measures are prompt, FN did not affect the delivery of chemotherapy and thus compromise survival.

Outcomes in Adult Acute Promyelocytic Leukemia: A Decade Experience.

BACKGROUND: Acute promyelocytic leukemia (APL), a distinct variant of acute myeloid leukemia (AML), accounts for 10% of AML cases. Over the past decade, APL has emerged from a highly fatal disease to a highly curable one. The published data on outcomes of APL from India are scant. The present study was designed to analyze the clinicopathologic features and outcomes in adult APL. MATERIALS AND METHODS: The present report is a single institutional, observational, retrospective study, and data of patients diagnosed with APL from 2006 to 2018 were analyzed. All patients with APL, diagnosed by morphology and confirmed by reverse transcriptase polymerase chain reaction (promyelocytic leukemia/retinoic acid receptor alpha) and over 18 years of age, were included in this study. SPSS software v25.1 was used for statistical analysis. RESULTS: A total of 1396 patients with AML were seen between January 2005 and June 2018, of which 190 (13.6%) had APL. Of these, 111 patients met the inclusion criteria and were analyzed. The median age at presentation was 33 years (range, 19-60 years). The median duration of symptoms before presentation was 15 days (range, 3-180 days). High risk, intermediate risk, and low risk were seen in 43.3%, 41.4%, and 15.3% of patients, respectively. At the end of induction chemotherapy, 88 (79%) patients achieved complete hematologic remission, and 23 (21%) succumbed during induction. The median time to attain complete hematologic remission was 30 days (range, 19-47 days). At a median follow-up of 34 months, the event-free survival and overall survival were 69.3% and 74.7%, respectively. On univariate analysis, bcr3 variant and high-risk category at presentation had significant impact on event-free survival (P = .029 and P = .003, respectively) and overall survival (P ≤ .001 and P = .007, respectively). On multivariate analysis, only high risk at presentation was significant for event-free survival (P = .04) and overall survival (P = .02). CONCLUSION: APL constituted one-tenth of patients with AML. The majority of patients were high risk at presentation. Sanz high risk category and bcr3 variant at presentation had significant impact on outcomes in APL.

Outcomes of Adult Ewing Sarcoma Treated with Multimodality Therapy: A Single-Institute Experience.

Introduction Ewing sarcoma (ES) is more common in children and relatively rare in adults. Adult ES has poor prognosis than children. Treatment approaches for adults have been extrapolated from pediatric experience. Data on adult ES are very few because of its rarity in adults. The present study was done to analyze the clinical profile and outcome of adult ES. Aims The aim was to study the clinical and pathological treatment and outcomes in adult ES. Subjects and Methods Between 2010 and 2017, a total of 73 ES patients with age more than 18 years were retrospectively analyzed. Survival analysis was done by plotting Kaplan-Meier curves. Results A total of 73 patients were diagnosed with ES during 2010 to 2017. Among them, 43 (58.9%) had localized disease with a median age of 24.5 years. Males were 44 (60.3%) and females were 29 (39.7). Pain (75.3%) was the most common symptom at presentation. Nine patients had incomplete details and were excluded from the analysis. Among 21 (28.8%) patients, the lung (61.9%) was the most common site of metastasis followed by the bone, bone marrow, and brain. The median number of chemotherapy cycles in the localized disease was 14 (range 1-17), and in metastatic disease, it was 4 (range 1-7). Univariate analysis was done with respect to age (< 25 vs. ≥25), gender, elevated or normal serum lactate dehydrogenase level, tumor size (< 8 cm versus ≥8 cm), site (axial versus extremity), and neoadjuvant chemotherapy (NACT) given or not. NACT had a significant impact on overall survival (OS) and the rest had no effect. At a median follow-up of 40 months, the 3-year OS in localized disease was 87.4%. In metastatic disease, the median OS was 13 months with 3-year OS of 26%. Conclusions Outcomes with multimodality therapy in adult ES patients with localized disease are comparable to that of a pediatric cohort. However, metastatic disease has poor survival.

Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia.

CONTEXT: In acute lymphoblastic leukemia (ALL), the most important prognostic factors are age, leukocyte count at presentation, immunophenotype, and cytogenetic abnormalities. The cytogenetic abnormalities are associated with distinct immunologic phenotypes of ALL and characteristic outcomes. AIMS: The present study was primarily aimed at analyzing the impact of cytogenetics on postinduction responses and event-free survival (EFS) in pediatric patients with ALL. The secondary objective was to study the overall survival (OS). SUBJECTS AND METHODS: A total of 240 patients with age <18 years and diagnosed with ALL between January 2011 and June 2016 were retrospectively analyzed. Cytogenetics was evaluated with conventional karyotyping or reverse transcriptase polymerase chain reaction. Based on cytogenetic abnormalities, the patients were grouped into five categories, and the outcomes were analyzed. RESULTS: Of the 240 patients, 125 (52%) patients had evaluable cytogenetics. Of these, 77 (61.6%) patients had normal cytogenetics, 19 (15.2%) had t(9;22) translocation, 10 (8%) had unfavorable cytogenetics which included t(9;11), hypodiploidy, and complex karyotype, 10 (8%) had favorable cytogenetics which included t(12;21), t(1;19), and high hyperdiploidy, 9 (7.2%) had miscellaneous cytogenetics. Seventy-one percent of patients were treated with MCP 841 protocol, while 29% of patients received BFM-ALL 95 protocol. The 3-year EFS and OS of the entire group were 52% and 58%, respectively. On univariate analysis, EFS and OS were significantly lower in t(9;22) compared to normal cytogenetics (P = 0.033 and P = 0.0253, respectively) and were not significant for other subgroups compared to normal cytogenetics. On multivariate analysis, EFS was significantly lower for t(9;22) and unfavorable subgroups. CONCLUSIONS: Cytogenetics plays an important role in the molecular characterization of ALL defining the prognostic subgroups. Patients with unfavorable cytogenetics and with t(9;22) have poorer outcomes.

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.

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.