Context: Oral submucous fibrosis (OSF) is a chronic, progressive condition and rise in incidence of this disease has been attributed to an increased uptake of betel nut and its products, especially among young people. Due to its potential for malignant transformation, easy and reliable techniques for its early detection are needed. Comet assay is a simple technique to detect and quantify single strand breaks, double strand breaks and alkali labile damages. Aims: The present pilot study was undertaken to assess the deoxyribonucleic acid (DNA) damage in OSF and healthy groups using comet assay. Settings and Design: The hospital-based study was conducted by evaluating buccal mucosal cells of 50 individuals in the age range of 16-47 years and comet assay was carried out for all the two groups under alkali conditions. Materials and Methods: Oral epithelial cells were obtained from buccal mucosa of each 25 cases of healthy and OSF groups were subjected to comet assay. DNA damage was evaluated by measuring the tail length. Statistical Analysis Used: Student's t-test and Turkeys-multiple post-hoc procedures were used to statistically analyze the obtained data. Results: Increase in the tail length in buccal epithelial cells of OSF group when compared with the healthy group was noted. Furthermore, there was a significant increase in the DNA damage with duration of habits. Conclusions: We conclude that increase in the tail length formation in OSF groups when compared to healthy groups; this indicates DNA damage in the oral epithelial cells. The comet assay is a relatively simple, but sensitive and well-validated tool for measuring strand breaks in DNA in single cells.

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We present a case of pilomyxoid astrocytoma (PMA) in a 35-year-old Asian male with history of paraparesis for last 6 months. A contrast-enhanced magnetic resonance imaging of the spine revealed an intramedullary mass lesion occupying most of the thecal sac at the level of 10 ^th and 11 ^th dorsal vertebrae, with extensive contrast enhancement. Spinal PMA in an adult is an extremely rare entity, with only two reported cases in the literature, until date. This appears to be the first reported case of spinal PMA in an adult with isolated thoracic spinal cord involvement.

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Objective: The clinical utility of Ki-67 in predicting response to neoadjuvant chemotherapy is limited by lack of an accepted validated method of assessment of Ki-67 and wide variations in the cut-offs. In this study, the interobserver variability in the estimation of Ki-67 proliferation index (PI) and its association with recurrence score (RS) was assessed. Materials and Methods: The interobserver variability was assessed between 3 pathologists in 27 invasive breast carcinomas that had also been analyzed for the RS (Oncotype DX). The guidelines proposed by International Breast Cancer Working Group (IBCWG) for analysis of Ki-67 were used. A Pearson correlation between the mean Ki-67 PI and the RS was calculated. Results: In the 27 tumors, the pathologists were in 89.1% agreement (intra-class correlation coefficient = 0.891, 95%, 0.806-0.945) for Ki-67 PI estimation. Furthermore, a strong positive correlation between Ki-67 and RS (r = 0.78464, P < 0.0001) was obtained. There were 10 cases with low risk (mean RS: 10.1; Ki-67 range: 3-33%); 13 with intermediate risk (mean RS: 21.4; Ki-67 range: 6-43%) and 3 with high risk (mean RS: 53; Ki-67 range: 55-91%). Conclusion: Conventional evaluation of Ki-67 index is reproducible using the method suggested by the IBCWG. The wide range of Ki-67 PI in low and intermediate risk groups and the unexpectedly high Ki-67 PI in some low risk carcinomas limit its use as a predictive measure.

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Aim: Recent progress in proteomics studies profiled that serum proteins of cancer patients and those of normal individuals have altered cancer antigen and acute phase protein expression for distinct types and stages of cancer. In our study, correlation between carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9, CEA and C-reactive protein (CRP), CEA and alpha-1 antitrypsin (A1AT) were evaluated in gastric and colon cancer patients. Materials and Methods: CEA was estimated by solid phase, two-site sequential chemiluminescent immunometric assay, CA19-9 by solid phase enzyme-linked immunosorbent assay, CRP by latex turbidimetry method and A1AT by turbidimetry method. Results: A significant correlation was seen in levels of CEA and CA19-9 in gastric (r = 0.457, P < 0.001) and colon cancer (r = 0.451, P < 0.001) patients. Correlation between CEA and CRP was significant in gastric (r = 0.462, P < 0.001) and colon cancer (r = 0.759, P < 0.001) patients and between CEA and A1AT also, correlation was found to be significant in gastric (r = 0.631, P < 0.001) and colon cancer patients (r = 0.516, P ≤ 0.001). Conclusion: Serum acute-phase protein concentrations, when combined with CEA increases the sensitivity of CEA and provide substantial information concerning the diagnosis of gastrointestinal cancers. They have a definite role as a significant prognostic indicator which undoubtedly correlates with progression of cancer. Combined CEA and CA19-9 positivity reflected more biologic malignant properties and were significantly correlated with lymph node metastasis, hepatic metastasis and lower rates of curative resection. Surgical outcomes of patients who were CEA and CA19-9 positive were poorer than those of patients with normal CEA and CA19-9 levels.

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Trichilemmal carcinoma (TLC) is a rare unusual malignant adnexal neoplasm arising from the external hair sheath. Diagnosis of this condition is essential as it is considered as a low grade carcinoma with low metastatic potential following a relatively benign clinical course. Unlike other high grade malignant skin neoplasms, TLC requires a different approach to treatment planning. We describe an unusual case of TLC presenting as cutaneous horn in a 60-year-old lady on the right side of the neck.

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Aims: Cancer stem cells (CSCs) are population of cells present in tumors, which can undergo self-renewal and differentiation. Three-dimensional (3D) in vitro models mimic features of the in vivo environment and provide unique perspectives on the behavior of stem cells. Materials and Methods: In this study, MDA-MB 231 cells were grown in two-dimensional (2D) monolayers and 3D spheroid formats and CSCs were isolated and grown as spheroids. The isolated CSCs were subjected to molecular studies for detection of CD44, CD24, MMP1, ABCG2, ALDH1, and GAPDH markers. Results: The monolayer of CSCs grown as spheroids showed better growth rate than the MDA-MB 231 cells, which shows the efficacy of 3D spheroid format of growing CSCs. CD44 show increased expression in spheroids compared to 2D culture of MDA-MB 231. ALDH1 a key marker of breast stem cells was highly expressed in BCSCs and MDA-MB 231 grown in 3D, while being absent in CSCs and MDA-MB 231 cells grown in 2D. Conclusions: The CSCs grown as spheroids showed better growth rate, which showed the efficacy of 3D spheroid format for CSCs culture. Since the association between BCSCs prevalence and clinical outcome and the evidence presented in this study support key roles of CSCs in breast cancer metastasis and drug resistance, it has been proposed that new therapies must target these cells.

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Phyllodes tumor is a rare breast tumor, with neoplastic epithelial and stromal components for <1% of all breast neoplasms. Phyllodes tumors form a spectrum from benign tumors, similar to fibroadenomas, of malignant tumors with a propensity for rapid growth and metastatic spread. High-grade malignant phyllodes tumor is a very rare, but aggressive breast malignancy and forms approximately 25% of all phyllodes tumors. We report a case of a 44-year-old female who presented with a painless left breast lump for 4 months duration. The mass was >10 cm in size and firm in consistency. She underwent left mastectomy. The histopathology revealed a malignant phyllodes tumor with sarcomatous stromal overgrowth and heterogeneous chondro and osteosarcomatous differentiation. At 2 months after surgery, she reported to us with secondaries in bilateral lungs. We planned palliative chemotherapy in view of good general condition of the patient and lung metastasis. Chemotherapy included ifosfamide, adriamycin and cisplatin as per standard regimen every 3 weekly. After three cycles, her lung metastasis cleared completely. It was planned to continue same chemotherapy for six cycles.

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Objective: To determine time delay from the onset of initial symptoms to diagnosis of primary lung cancer. Materials and Methods: Selected information was captured from 49 consecutive pathologically proven cancer lung patients presenting to a tertiary respiratory centre during 1 ^st January to 30 ^th June 2012 using semi-structured interview schedule. All patients underwent suitable protocol based diagnostic work-up and referral. Results: Background profile of patient was as follows: Male:Female = 7.1:1; mean age was 61.2 (±9.7) years; Nine out of 49 (18.4%) patients were illiterate; Forty-three out of 49 (87.8%) belonged to rural native place; Forty-three out of 49 (87.7%) were smokers with 25 years as median pack-years. Histological profile showed that adenocarcinoma (40.8%) was the predominant form followed by small cell carcinoma (32.7%). Time (median) delay in diagnosis was 3.0 days (home remedies/quack therapy), 60.0 days (primary/secondary level) and 8 days at tertiary level. Twenty seven of 49 patients (55.1%) presented in stage-IV. Higher proportion of patients residing outside the district of study institute had longer delay in diagnosis but did not reach statistical significance (P > 0.05). The most important patient reasons for the delay in diagnosis was procrastinate/did not took symptoms seriously (19/49, 38.7%); no-body to escort (13/49, 26.5%), long distance (5/49, 10.2%), financial constraints (4/49, 8.1%), preferred local practitioner (2/49, 4.0%), family commitment/marriage (2/49, 4.0%), fear of death (1/49, 2.0%) and no reason cited (3/49, 6.1%). Three patients were inadvertently diagnosed as tuberculosis and hence the delay. Conclusion: Patient presented at a higher stage within a short span of time; however, there is scope of increasing health system capacity at primary/secondary level including sensitization training, health communication and appropriate referral to higher center.

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Context: There is controversy regarding the radiotherapeutic dose fractionation in brain metastases (bm). Aims: The aim of this study is to analyze the treatment outcomes in patients with multiple bm. Settings and Design: Prospective, randomized study. Subjects and Methods: Patients with multiple bm with Eastern Cooperative Oncology Group performance status ≤2 were included. In arm-A patient received whole brain radiotherapy (WBRT) 30 GY in 10# over 2 weeks and in arm-B patients received 20 GY in 5# over 1 week. Assessment of improvement in clinical symptoms was done using Barthel's adjusted daily live (ADL) score. Assessment of radiological response was done using magnetic resonance imaging scan of brain after 3 months of completion of external beam radiation therapy. Acute radiation toxicity was assessed using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer acute radiation morbidity scoring. Statistical Analysis Used: Chi-square test was used to compare categorical variables between groups. Overall survival was computed by Kaplan-Meier survival analysis and Log-Rank test used for comparison of survival plots. For change in quality-of-life during treatment and follow-up, repeated measures ANOVA were used. Results: In both arms, there was a significant improvement in ADL score after treatment, but when two arms were compared, no significant difference was found between the two treatment arms. There was no statistically significant difference in response or morbidity between the two treatment arms. Median survival was 29 weeks in arm-A compared to 25.86 weeks in patients arm-B. Kaplan-Meier Survival curve analysis shows no significant difference in survival between the two arms. Conclusions: 20 GY in 5 fractions is equally effective with that of the 30 GY in 10 fractions for WBRT in bm. In the palliative setting short duration of treatment with minimum discomfort to the patient is desirable. Hence, we can opt for 20 GY in 5 fractions in poor performance status patients and 30 GY in 10 fractions in patients with good performance status.

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Castleman's disease, or angiofollicular lymph node hyperplasia, is a relatively rare disorder characterized by the benign proliferation of lymphoid tissue. Two clinical entities have been described: Unicentric with the disease confined to a single anatomic lymph node and multicentric characterized by generalized lymphadenopathy and more aggressive clinical course. Also, three histopathological subtypes have been described: Hyaline-vascular, plasma cell, and a mixed variant. Preoperative diagnosis of hyaline-vascular Castleman's disease is difficult, and the definitive result is based on postoperative pathological findings. The gold standard therapy is the complete surgical excision.

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Metastases to adrenal glands from solid tumors are fairly common. The incidence varies from 17.6% to 35% in lung primaries and 13-27% in other malignancies. Most of these lesions are clinically occult. Historically, the role of radiotherapy was limited to palliation of pain in symptomatic lesions. However, with the advent of more conformal techniques such as stereotactic body radiation therapy, the focus has shifted to treatment of such lesions with curative intent in selected situations. We treated a patient of non-small cell lung cancer with solitary adrenal metastasis, following partial response to chemotherapy. The adrenal lesion was treated with CyberKnife while the lung lesion was treated with intensity modulated radiotherapy, both with curative intent.

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Peutz-Jegher's syndrome (PJS) is an autosomal dominant disorder characterized by numerous hamartomatous polyps in the gastrointestinal tract (GIT) and pigmented muco-cutaneous lesions. We present here a case of a maltoma associated with multiple hamartomatous polyps detected in a post-operative ileocolic specimen of a 28-year-old man. Prior to this, he had undergone surgery for intussusception when similar polyps were noted in the small bowel. Upper GIT endoscopy also confirmed the diffuse presence of such polyps. A clinico-pathological diagnosis of PJS was made, which by itself is rarely encountered. Furthermore, the detection of mucosa associated lymphoid tissue lymphoma/maltoma in a background of PJS is remarkably unique in this case, for which it has been reported.

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Tubulocystic renal cell carcinoma (TC-RCC) is a recently described rare subtype of RCC. Less than 70 cases have been reported until date. The concurrent papillary RCC (P-RCC) and TC-RCC has been documented many times in the literature, but the co-occurrence of clear cell RCC (CC-RCC) and TC-RCC is very rare. We are probably describing the third case of TC-RCC occurring with CC-RCC in a 62-year-old male who presented with heaviness of left upper abdomen and dull intermittent pain in the left flank. Grossly, there was two distinct parts in the total nephrectomy specimen. The larger solid part displayed the histopathological features of CC-RCC and the smaller spongy part revealed the features of TC-RCC.

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"Acinic cell carcinoma (ACC) with lymphoid stroma" represents a separate subgroup of salivary gland tumors with a thin fibrous capsule, a microfollicular growth pattern and a prominent lymphoid infiltrate completely surrounding the epithelial component. Lack of familiarity with this entity may create diagnostic problems. Recognition of this rare histologic variant is also important because it behaves far less aggressively than the conventional ACC. We describe cytological and histological findings in one such rare occurrence in the parotid gland of a 27-year-old female. Fine-needle aspiration of this mass revealed cohesive clusters of relatively uniform cells revealing mild pleomorphism, nuclear overlapping, frequent microacinar pattern, abundant granular/vacuolated/foamy/oncocytoid basophilic cytoplasm with ill-defined cytoplasmic borders. Background showed small mature lymphocytes, reactive lymphoid cells and lymphohistiocytic aggregates. Histopathological examination of resected tumor ACC with tumor cells containing periodic acid-Schiff positive diastase resistant granules arranged predominantly in microcystic pattern and surrounded by dense lymphoid stroma containing lymphoid follicle with prominent germinal centers.

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Synovial sarcoma (SS) is a rare malignant neoplasm comprising 8% of mesenchymal tumors. Only few reports defining cytological findings in SS of anterior chest wall have been described in the literature. We hereby report a case of biphasic SS of anterior chest wall, which was diagnosed on fine-needle aspiration. Cytological smears revealed bimodal cell population comprising of spindle cells and epithelial cells. Spindle cells were arranged in dense clusters, having elongated nuclei, fine nuclear chromatin and scanty cytoplasm. Epithelial cells were arranged in a glandular pattern, with central to eccentric, round nuclei, fine nuclear chromatin and scanty cytoplasm. A possibility of biphasic SS was suggested, which was later confirmed on histopathology and immunohistochemistry. Prompt diagnosis and aggressive surgical resection is mandatory for primary SS of the chest wall because of its aggressive behavior.

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Metaplastic carcinomas of breast are uncommon, representing 0.3% of invasive carcinomas of breast. We are reporting two cases of metaplastic carcinoma breast, one revealing rhabdomyoblastic and spindle cell differentiation and other revealing osteoclast like giant cells. Both were estrogen receptor, progesterone receptor and Her2u negative on immunohistochemistry. Early diagnosis of metaplastic carcinomas is essential as these tumors are usually triple negative and hence, do not respond to transtuzumab. Metaplastic carcinomas typically express HER1/epidermal growth factor receptor (EGFR), thus majority of metaplastic carcinomas are treated with EGFR inhibitors such as geftinib and cetuximab. Also, metaplastic carcinomas are associated with a worse prognosis with a disease free survival rate being 78.1% in metaplastic breast carcinomas compared with 91% in infiltrating duct carcinomas.

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Delays in breast cancer diagnosis are associated with negative clinical effects. The main causes are protocol violations, clinical errors, radiological errors, pathological errors and patient fault. Although rare, breast lump that is clinically benign, but has undergone rapid growth should alert the clinician of the possibility of underlying sarcoma. We report a case of a 42-year-old female patient with breast sarcoma who developed recurrence of sarcoma along with ipsilateral pleural effusion. Owing to rarity of the disease and controversies involved in the management, there is no protocol for management of these patients.

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Aims: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma (NHL) with frequent extra nodal (EN) presentation. The overall occurrence of lymphomas has been increasing; however, those of EN-NHL have been increasing much more rapidly. There is limited data found on EN-DLBCL in the Indian population and hence we carried out this retrospective observational study of primary EN-DLBCL at our center in Southern India. Materials and Methods: A total of 90 consecutive cases diagnosed as EN-DLBCL (according to the standard criteria) by tissue biopsy confirmed by immunohistochemistry between 2007 and 2011 were included. Staging workup including computed tomography of neck, thorax and abdomen and pelvis, bone marrow aspiration and biopsy was done and International Prognostic Index (IPI) calculated. Staging was according to Cotswold's modification of Ann Arbor. The actuarial survival analysis was performed by Kaplan-Meier. Data were analyzed using the SPSS (version 16) statistical software. Results: The median age in this study was 49 years (18-88) with results showing EN-DLBCL to be 1.36 times more common in males. Advanced stages were seen in 15 subjects (16.6%) and bulky disease in 13 subjects (14.4%). CD20 was positive in 89 (98.8%) while 32 had high serum lactate dehydrogenase. According to the IPI most were low-risk-56 (66.6%). Overall response rate for the various combination chemotherapies was 85.7% with complete response in 62.3%. The overall survival range spanned from 2 to 123 months. Univariate analysis showed only bulky disease was associated with inferior survival. Conclusions: EN-DLBCL was present at an early age compared to nodal DLBCL, present more often in early stage and low IPI score. Chemoimmunotherapy with radiotherapy to the EN or bulky site is the standard treatment at present.

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Background: Loss of expression of cadherins by promoter hypermethylation has been described in many epithelial cancers, and it may play a role in tumor cell invasion and metastasis. Previously, we reported that E-cadherin gene is frequently methylated in epithelial ovarian cancer. Aim: The aim of this study was to compare the promoter hypermethylation of H-cadherin gene in ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Materials and Methods: We examined the promoter methylation of the H-cadherin gene in 134 epithelial ovarian carcinomas (EOC), 23 low malignant potential (LMP) tumors, 26 benign cystadenomas and 15 normal ovarian tissues. Methylation was investigated by methylation specific polymerase chain reaction (MSP) and the results confirmed by bisulfite DNA sequencing. Relative gene expression of H-cadherin was done using quantitative reverse transcriptase PCR on 51 EOC cases, 9 LMP tumors, 7 benign cystadenomas with 5 normal ovarian tissues. Results: Aberrant methylation of H-cadherin was present in 20 of 134 (15%) carcinoma cases, 2 of 23 (09%) LMP tumors and 1 of 26 (4%) benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of H-cadherin was significantly down-regulated in EOC and LMP tumors than the corresponding normal tissues, whereas the expression level was normal in benign cystadenomas. A significant correlation of H-cadherin promoter methylation was observed with reduced gene expression in EOC. The prevalence of H-cadherin methylation was associated significantly with stage, histopathological grade, and menopausal status of the patient. H-cadherin methylation also had significant association with recurrence and differentiation of tumor. Conclusion: Our findings suggest an association between H-cadherin methylation, tumor progression and recurrence in EOC.

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Introduction: Concurrent single agent cisplatin (CDDP) with radiotherapy (RT) improves outcomes in locally advanced squamous cell carcinomas of the head neck (LA-SCCHN). CDDP at 100 mg/m ² at 3 weekly intervals raise compliance, hospitalization, and supportive care issues. Low dose daily CDDP was delivered with RT to evaluate its compliance, long-term safety and efficacy. Patients and Methods: During the period of month between November 2005 and May 2007, 52 patients of stage III/IV LA-SCCHN were given with conventional RT in a phased manner (dose-70 Gy/35 fractions/6 weeks) along with daily CDDP (6 mg/m ² ; capped 10 mg-30 cycles) over 6 weeks. No hospitalization or antiemetic cover was planned. Compliance, acute and late toxicity were recorded as per Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system and survival outcomes were evaluated. Results : The median follow-up was 63 months. 43 (83%) cases complied with RT schedule and >28 cycles of CDDP was administered in 38 (73%) cases. Confluent mucositis was seen in 65%, Grade III/IV dysphagia in 67%; 77% required enteral feed and hospitalization in 15%. There were four treatment related deaths. At 5 years, the loco-regional control was 25% (median-11 months) and the overall survival was 31% (median-11 months). The 5 years actuarial rates of late Grade III/IV toxicity was 24%. Late swallowing difficulty/aspiration were seen in 17%; xerostomia-40%; ototoxicity-6%; nephrotoxicity-4%; and no second malignancy. Conclusion: Low dose cisplatin with moderately accelerated RT schedule appears feasible and logistically suitable "out-patient" option without increasing long-term toxicity in LA-SCCHN cancer region.

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Introduction: Primary central nervous system lymphoma (PCNSL) is relatively uncommon malignancy with potentially aggressive behavior. The standard management of PCNSL is high-dose methotrexate (HD-MTX) based chemotherapy and whole brain radiotherapy (WBRT). This treatment is associated with toxicity and requires in-patient admission with intensive monitoring. An alternative approach with WBRT followed by systemic chemotherapy with standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen can be used in community settings in a cohort of patients who cannot receive the standard treatment due to logistic reasons. Materials and Methods: We retrospectively reviewed the patients of PCNSL treated in our institute from January 2004 to May 2010. A total of 39 patients of PCNSL were treated. All patients received WBRT followed by systemic chemotherapy with standard CHOP regimen. Survival analysis was done with Kaplan-Meier method using Statistical Package for Statistical Analysis (SPSS version 15). Prognostic factor influencing survival was evaluated using Cox regression analysis. Toxicity and overall treatment compliance analysis was also evaluated. Results: Overall compliance to RT and chemotherapy was excellent, 37 (94.9%) patients completed planned treatment within the stipulated time period. Grades II-III skin toxicity was seen in three patients and Grade II hematological toxicity was seen in two patients. At 1 month after completion of planned treatment, 15 patients had no symptoms and 20 patients had significant improvement while four patients deteriorated clinically while radiological imaging showed complete response, partial response, progression of disease in 22, 12 and 5 patients respectively. Mean overall survival (OS) was 36.34 months and median OS was 20.0 months with 3-year actuarial OS of 38%. Age of 50-year was a significant (P < 0.05) prognostic factor for survival. Conclusions: The standard of care in management of PCNSL is HD-MTX based chemotherapy. However, considering poor compliance and tolerability to treatment in low resource countries in routine clinical setting, WBRT followed by systemic chemotherapy with standard CHOP regimen for treatment of PCNSL demonstrate reasonably good outcome. This regimen is quite economic as well as simple to implement.

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