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AIM: The aims of this study were to assess the feasibility of performing an extralevator abdominoperineal excision (ELAPE) after neoadjuvant chemoradiation (NCRT), to compare the rates of circumferential resection margin (CRM) involvement and intra-operative perforation (IOP) of the specimen, and to assess the amount of tissue removed around the muscularis propria (MP)/internal sphincter (IS) of the lower rectum in patients with low rectal cancer undergoing ELAPE compared with conventional abdominoperineal excision (CAPE) after NCRT. METHOD: This was an open-label, parallel-arm pilot randomized trial conducted in India. Twenty patients were randomized to one of the study arms. The surgical specimens were fixed, serially cross-sectioned and photographed. Using specialized morphometry software, the amount of tissue resected with each operation was measured. RESULTS: There was a nonsignificant trend towards more IOPs (30% vs 0%, P = 0.06) and a higher CRM involvement rate (40% vs 20%, P = 0.32) in the CAPE arm. ELAPE removed a significantly greater amount of tissue around the IS/MP when compared with CAPE (mean ± SD: 1911.39 ± 382 mm2 vs 1132.03 ± 371 mm2 , P < 0.001). The mean distance from the IS/MP to the CRM was significantly greater in the ELAPE arm both in the posterior (mean ± SD: 28.28 ± 3 mm vs 9.63 ± 3 mm, P < 0.001) and lateral (mean ± SD: 13.69 ± 3 mm vs 9.72 ± 3 mm, P = 0.009) parts of the rectum but not in the anterior part (mean ± SD: 6.74 ± 2 mm vs 6.10 ± 4 mm, P = 0.64). The short-term morbidity was not significantly different between the two procedures. CONCLUSION: ELAPE removed more tissue in the lower rectum and resulted in a lower rate of IOP and CRM involvement when compared with CAPE, even after NCRT.

Asunto(s)

Abdomen/cirugía , Márgenes de Escisión , Perineo/cirugía , Neoplasias del Recto/cirugía , Recto/cirugía , Adulto , Canal Anal/patología , Canal Anal/cirugía , Quimioradioterapia , Femenino , Humanos , Perforación Intestinal/etiología , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Proyectos Piloto , Neoplasias del Recto/patología , Recto/patología , Resultado del Tratamiento

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INTRODUCTION: Rituximab (R)-CHOP improves survival over CHOP in diffuse large B-cell lymphoma (DLBCL). The availability of biosimilar rituximab in India has increased access of this drug. We report on the impact of treatment on outcomes with special emphasis on the impact of biosimilar rituximab and radiation. METHODS: Outcomes of adults (age 15-60 years) treated with CHOP+/- Rituximab radiation were analyzed retrospectively to look at baseline features, treatment, and event-free and overall survival (EFS and OS). RESULTS: In the period 2000-2013, 444 patients (median age 47 years: 15-60; males: 288 [65%]; Stage III/IV: 224 [50%]; age-adjusted international prognostic index [aaIPI] Score 2 or 3 in 50%) received either CHOP (n = 325 [73%]) or RCHOP (n = 119 [27%]) therapy. Biosimilar rituximab and the original were used in 95 (80%) and 24 (20%) patients, respectively. Radiation was given in 134 (30%) patients (Stages I and II, 100/220 [45%] and Stages III and IV, 34/224 [15%]). After a median follow-up of 46 (0.2-126) months, the 5-year EFS and OS were 59% and 68%, respectively. The factors predicting inferior EFS and OS were age> 40 years, performance status 2-4, Stage III/IV, hemoglobin <12 g/dL, the aaIPI Score 2 or 3, and nonuse of rituximab and radiation. Radiation used in early stage disease benefitted all subgroups regardless of bulky disease, use of rituximab, or the number of cycles of chemotherapy. Addition of rituximab improved survival across all categories of aaIPI. CONCLUSION: Availability of biosimilar rituximab has increased access and survival of patients with DLBCL in India. Radiotherapy improved outcomes in early stages.

Asunto(s)

Antineoplásicos Inmunológicos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/radioterapia , Radioterapia/métodos , Rituximab/uso terapéutico , Adolescente , Adulto , Antineoplásicos Inmunológicos/farmacología , Biosimilares Farmacéuticos/farmacología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Rituximab/farmacología , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND: Combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarabazine) cures ∼70% of patients with advanced Hodgkin's lymphoma (aHL, stages IIB, III and IV) while more toxic escalated BEACOPP (EB, combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone) increases cure rates to 85%. Patients with a positive interim positron emission tomography-computerized tomography (PET-CT) scan after two cycles (PET-2) of ABVD have very poor outcomes with continued ABVD. Intensifying therapy with EB in PET-2-positive patients ('response-adapted therapy') may improve cure rates, whereas the negative patients can continue ABVD alone. PATIENTS AND METHODS: Eligible patients with newly diagnosed aHL received two cycles of ABVD and underwent PET-2 (scored with semi-quantitative 5-point visual criteria, 'Deauville score'). PET-2-negative patients continued four additional cycles of ABVD, whereas PET-2-positive patients received four cycles of EB. A phase II sample size of 50 was estimated keeping the lower and higher proportion of rejection of the event-free survival (EFS) as 70% and 85%, respectively. RESULTS: Fifty patients [median age 28 (12-60) years; male : female: 39 : 11; stages: IIB-3 (6%), III-29 (58%) and IV-18 (36%); International Prognostic Score (IPS): 0-3: 34 (68%); 4-7: 16 (32%)] were enrolled; 49 underwent PET-2. Eight (16%) were PET-2-positive, whereas 41 (84%) were negative. Forty-seven were evaluable for EFS and all 50 for overall survival (OS). The 2-year EFS was 76% (95% CI: 68-83) and OS was 88% (95% CI: 82-94). PET-2 was strongly prognostic-2-year EFS, negative versus positive: 82% versus 50%; P = 0.013. CONCLUSION: PET-2 response-adapted strategy could not achieve EFS of 85% in aHL. However, escalated therapy improved outcomes in PET-2-positive patients compared with historical data. TRIAL REGISTRATION: CTRI/2012/06/002741 (http://www.ctri.nic.in) and NCT01304849 (http://www.clinicaltrials.gov).

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Niño , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Humanos , India , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversos , Adulto Joven

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INTRODUCTION: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)-reverse transcription-polymerase chain reaction (RT-PCR), the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings. MATERIALS AND METHODS: Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P-AKT) and thyroid transcription factor-1 (TTF-1) on above patient's sample, and the results were compared with EGFR mutation tests. RESULTS: EGFR mutation was positive in 34 of 85 patients (40%). P-AKT and TTF-1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF-1 simultaneously. CONCLUSION: P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.

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Adenocarcinoma/genética , Biomarcadores , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Proteína Oncogénica v-akt/genética , Factores de Transcripción/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Fosforilación , Reacción en Cadena de la Polimerasa , Pronóstico , Factor Nuclear Tiroideo 1

RESUMEN

BACKGROUND AND OBJECTIVES: Bendamustine has been recently approved for the treatment of low-grade lymphoproliferative disorders. There is little data on the effectiveness or toxicity of this drug outside the trial setting. This is the first report on the use of bendamustine from the Indian subcontinent. SETTINGS AND DESIGN: Retrospective descriptive analysis of response and side effects of bendamustine in eight patients with chronic lymphocytic leukemia and eight patients with follicular lymphoma. METHODS: Data was collated from a review of case records. We examined any association between side effects and clinical parameters. RESULTS: The median age of patients was 52 years and three-quarters had received prior treatment with alkylators or fludarabine. Three different protocols of bendamustine were used (single agent, in combination with rituximab or in combination with vincristine and prednisolone). The overall response rate was 80% (47% complete response, 33% partial response, and 20% progressive disease). The drug was well tolerated with very few grade 3/4 toxicities. More than half the patients (9/16) developed a characteristic erythematous, papular skin rash that resolved after completion of chemotherapy. CONCLUSION: Bendamustine is a safe and useful addition to the drug arsenal against lymphoproliferative disorders. A peculiar skin rash was the commonest side effect noted in Indian patients treated with this drug.

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Antineoplásicos Alquilantes/efectos adversos , Exantema/etiología , Compuestos de Mostaza Nitrogenada/efectos adversos , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Clorhidrato de Bendamustina , Quimioterapia Combinada , Exantema/patología , Femenino , Humanos , India , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Compuestos de Mostaza Nitrogenada/uso terapéutico , Prednisolona/uso terapéutico , Estudios Retrospectivos , Rituximab , Vincristina/uso terapéutico

RESUMEN

This study investigated the prevalence of Epstein-Barr virus (EBV) infection and its association with P53 expression in a panel of 87 previously untreated nodal non-Hodgkin lymphomas (NHLs) from India. Polymerase chain reaction specific for Epstein Barr nuclear antigen 1 (EBNA1) and EBNA-3C was performed on the lymphnode tissue DNA, while P53 expression was analyzed by immunohistochemistry. EBV, predominantly type A strain, was detected in 27/87 (31%) nodal lymphoid malignancies, 11/46 diffuse large B-cell lymphomas, 6/17 follicular lymphoma, 4/6 anaplastic large cell lymphomas (ALCL), 5/11 peripheral T-cell lymphomas (PTCL) and 1/7 lymphoblastic lymphomas. EBV infection was more frequently observed in a specific subset of nodal NHL, suggesting a causative role of EBV infection in the pathogenesis of ALCL and PTCL. There was no significant association between EBV and P53 expression in our series of NHL patients.

Asunto(s)

Infecciones por Virus de Epstein-Barr/metabolismo , Regulación de la Expresión Génica , Linfoma no Hodgkin , Proteína p53 Supresora de Tumor/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Antígenos Nucleares del Virus de Epstein-Barr/genética , Femenino , Humanos , Inmunohistoquímica , India , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , Mutación , Análisis de Secuencia , Proteína p53 Supresora de Tumor/genética