Spectrum of metastatic neoplasms of the brain: A clinicopathological study in a tertiary care cancer centre.

BACKGROUND: While brain metastases (BM) are the most common causes of neurologic disorders in patients with known systemic malignancies, they can often be the initial manifestations of an undetected primary elsewhere. BM are major causes of morbidity and mortality in cancer patients. AIMS: We describe a mixed population (data from both retrospective and prospective collection) having a BM from a solid tumor. We report the percentage distribution of the most frequent types of BM, confirming the data published in the literature. This paper may play a role in presenting the Southeast Asian reality compared with the Western countries. SETTING: A tertiary-care cancer centre. MATERIALS AND METHODS: Data for 4 years were retrieved from the records of the Department of Pathology of our institute. Hematolymphoid and meningeal tumors were excluded. Hematoxylin and eosin (H and E) stained slides were reviewed, and in cases with an unknown primary, immunohistochemistry (IHC) was advised. The panel of markers was chosen based on the histomorphology on H and E sections. IHC was done in cases with an unknown primary where paraffin blocks were available. RESULTS: Lung cancer was found to be the most common primary malignancy (n = 30; 48.4%) followed by breast cancer (n = 13; 21%), colorectal cancer (n = 6; 9.6%), and skin cancer (melanoma) [n = 3; 4.8%]. CONCLUSION: The incidence of BM from lung and breast cancer was similar to that seen in the Western studies. However, BM from colorectal cancer and melanoma show a higher and lower incidence, respectively, in comparison with the Western literature.

Delays in diagnosis and treatment of breast cancer: a multinational analysis.

BACKGROUND: Reducing treatment delay improves outcomes in breast cancer. The aim of this study was to determine factors influencing patient- and system-related delays in commencing breast cancer treatment in different countries. METHODS: A total of 6588 female breast cancer patients from 12 countries were surveyed. Total delay time was determined as the sum of the patient-related delay time (time between onset of the first symptoms and the first medical visit) and system-related delay time (time between the first medical visit and the start of therapy). RESULTS: The average patient-related delay time and total delay time were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively. Longer patient-related delay times were associated with distrust and disregard, and shorter patient-related delay times were associated with fear of breast cancer, practicing self-examination, higher education level, being employed, having support from friends and family and living in big cities. The average system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made by an oncologist versus another physician, higher education level, older age, family history of female cancers and having a breast lump as the first cancer sign were associated with shorter system-related delay times. Longer patient-related delay times and higher levels of distrust and disregard were predictors of longer system-related delay times. CONCLUSIONS: The delay in diagnosis and treatment of breast cancer remains a serious problem. Several psychological and behavioural patient attributes strongly determine both patient-related delay time and system-related delay time, but their strength is different in particular countries.

T-Cell Prolymphocytic Leukemia: An Experience from a Tertiary Cancer Centre in South India.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable. Materials andMethods: This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes. Results: Seven patients were diagnosed as T-PLL over a period of 5 years. The median age at diagnosis was 51 years. In the present series, 6 patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4 patients. The median survival was 5 months with different chemotherapy (CT) regimens (5 patients treated with CT and 2 received best supportive care). Conclusion: T-PLL is a rare disease with no definite treatment guidelines. At present, the best outcomes are achieved if treatment with alemtuzumab is followed by stem cell transplant, but the disease invariably relapses. Countries where affordability remains a big challenge, the best approach needs to be defined beyond the monoclonal antibodies and transplant.

Correlation of BMI with breast cancer subtype and tumour size.

BACKGROUND: Breast cancer is a heterogeneous disease which is divided broadly into luminal, HER2 and basal type based on molecular profiling. Increased body mass index (BMI) has been associated with the risk of developing breast cancer but the association based on molecular subtype remains conflicting. METHODS: This was an observational study carried out over a period of 2 years. Nonmetastatic breast cancer patients were evaluated for the tumour subtype based on surrogate markers (ER, PR and HER2). The BMI of these patients was correlated with the tumour subtype and size. RESULTS: We studied 476 patients with breast cancer with the median age of 46 years (range, 25-86) and 58% were premenopausal. The mean BMI of the cohort was 24.1, which was significantly higher in postmenopausal women (24.9 versus 23.6, p < 0.05). Overall, only 10% of patients were obese. The mean BMI in the luminal, HER2 and TNBC subtypes was 24.7, 22.4 and 23.9, respectively (p < 0.01). Also, the mean tumour size in luminal, HER2 and TNBC subtype was 4.02, 3.80 and 4.27 cm, respectively (p = 0.158). CONCLUSION: The average BMI was higher in patients with luminal subtype followed by TNBC and lowest for HER2 at the time of diagnosis. The mean tumour size was numerically higher for TNBC and lowest for HER2 subtype although the difference was not statistically significant. Larger studies may provide clarity of association between the BMI and tumour subtype.

Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin's lymphoma which occurs in both immunocompromised and immunocompetent patients. It has an overall poor prognosis in spite of a multimodality treatment approach including chemotherapy and radiotherapy. This study attempts to further delineate the clinicopathological, immunohistochemical, and radiological profile of PCNSL at Kidwai Memorial Institute of Oncology, Karnataka, India. MATERIALS AND METHODS: All the pathologically confirmed PCNSL cases between January 2010 and June 2016, at our center, were analyzed retrospectively. The influence of potential prognostic parameters on overall survival (OS) was investigated by log-rank test and Cox regression analysis. RESULTS: Of the 26 PCNSL patients, 17 (65.3%) were males. Median age at diagnosis was 42.5 years. None of the patients had HIV or Epstein-Barr virus positivity and only four patients (15.4%) had B-symptoms. The most common location in the brain was cerebral hemispheres in 15 patients (57%) and 10 patients (38.5%) had multiple intracranial lesions. Histologically, all were diffuse large B-cell lymphomas, except one case of anaplastic large cell lymphoma. Immunohistochemically, 18 patients (69%) had MUM 1 positivity and 20 cases (77%) belonged to nongerminal center subtype. DeAngelis protocol was followed in 24 patients (92%), and among this cohort, Memorial Sloan Kettering Cancer Center Class 1 (n = 17) and Class 2 (n = 7) patients had a median OS of 25 months and 11 months, respectively. CONCLUSION: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify more effective primary chemotherapy regimens to further improve the treatment outcome.

Plasma Epstein Barr viral load in adult-onset Hodgkin lymphoma in South India.

OBJECTIVE/BACKGROUND: Epstein Barr Virus (EBV) DNA load is increasingly being used as a noninvasive biomarker for detecting EBV association in lymphomas. Since there is a need of data from India, we undertook to prospectively evaluate plasma EBV DNA load as a marker of EBV association in newly diagnosed adult-onset Hodgkin lymphoma (HL). METHODS: EBV DNA was quantified using real-time polymerase chain reaction. In a subset of patients, an assay was validated qualitatively with EBV latent membrane protein-1 (LMP1) immunohistochemistry (IHC). Wherever possible, follow-up plasma samples post three cycles of chemotherapy were obtained. RESULTS: Over a period of 10 months, 33 newly diagnosed adult-onset HL were enrolled in the study. Pretherapy plasma EBV DNA was detectable in ∼49% (16/33) patients (viral loads range, 1.0-51.2×10(3)copies/mL) and undetectable in 30 voluntary blood donors. LMP1 IHC was positive in 56% of cases tested (14/25). Sensitivity and specificity of plasma EBV DNA with respect to LMP1 IHC were 86% and 100%, respectively. Of the eight patients in whom follow-up plasma was available, in five EBV baseline-positive patients EBV load reverted to negative postchemotherapy and corroborated with clinical remission. CONCLUSION: Plasma EBV DNA load estimation may be useful in detecting EBV-association and possibly monitoring the response to therapy in EBV-related HL especially in our country where EBV association of HL is higher than in developed nations.

Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients.

BACKGROUND AND OBJECTIVES: Febrile neutropenia (FN) is considered a medical emergency. Patients with hematological malignancies (HM) commonly experience FN. Broad spectrum antibiotics have to be started empirically to prevent complications. This study depicts the clinical profile, microbiological profile, antibiotic sensitivity pattern, and outcome in high risk HM. MATERIALS AND METHODS: In this prospective study, 72 patients with hematologic malignancies, diagnosed and treated for 108 high risk febrile neutropenic episodes from August 2011 to January 2013 at a Regional Cancer Center, in South India were analyzed. Cefoperazone-sulbactum was used as a first-line empiric antibiotic. RESULTS: Majority of the patients with FN episodes had acute myeloid leukemia. Overall culture positivity was 29.62%. The most common organisms isolated were Gram-negative bacilli (63.64%), with Escherichia coli being the most frequent pathogen. All Gram-negative organisms were sensitive to imipenem, whereas sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%, 63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone-sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone-sulbactum. CONCLUSIONS: In the hematologic malignancies particularly in acute leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone-sulbactum as a first line leads to satisfactory outcome in high risk FN and therapy should be tailored to the most appropriate antibiotics according to the bacterial culture results.

Management of febrile neutropenia in solid organ malignancies following chemotherapy.

BACKGROUND: Febrile neutropenia is a medical emergency and it requires immediate hospitalization for evaluation and administration of empiric broad-spectrum antibiotics. The present study was undertaken to analyze the infectious agents, choice of empiric antibiotics, and outcome in high-risk febrile neutropenia in the solid organ malignancies. MATERIALS AND METHODS: In this study, 92 high risk febrile neutropenic episodes were analyzed in 72 patients with solid organ malignancies. We used cefoperazone-sulbactum as an initial empiric antibiotic. Piperacillin/tazobactum or carbapenems were added to the patients who did not respond to initial antibiotic. RESULTS: Among the 92 episodes treated, most patients received first-line chemotherapy for locally advanced disease. Microbes were isolated in 25% of febrile neutropenic episodes. Gram-negative organism (61.70%) constituted the most common isolates. The most common microbes identified were E. coli and Staphylococcus aureus in blood, Klebsiella pneumonia in sputum and E. coli in urine culture. Patients who had been treated with cefoperazone-sulbactum improved clinically in 70.6% of febrile neutropenic episodes. Second- line antibiotics (piperacillin-tazobactum with amikacin) were required in 24% episodes, while another 5.4% episodes required third-line antibiotics (carbapenems). In this study, mortality was seen in 12% of febrile neutropenic episodes. Staphylococcus aureus was 100% sensitive to linezolid, teicoplanin, and vancomycin, whereas Gram-negative organisms were 100% sensitive to imepenem and meropenem. CONCLUSION: Cephaperazone-sulbactum is a reasonable initial choice for empirical therapy in high risk febrile neutropenic patients in solid organ malignancies.