Combined modality treatment: Outcome in patients with Hodgkin's lymphoma

Background: Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced stage HL is mainly treated with chemotherapy followed by radiation to the bulky site. This study examines the impact of CMT in early as well as advanced stage HL. Materials and Methods: From 2001 to 2011, 125 patients with Stage I to IV HL were analyzed. Median age of the patients was 25 years (range 12–68 years). CMT, chemotherapy, and radiation alone were given to 51, 64, and 10 patients, respectively. Chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was given to 100 patients, 6 patients received ABVD-like regimen, and 9 patients received cyclophosphamide, vincristine, procarbazine, and prednisone regimen. Radiotherapy (RT) was given to 61 (49%) patients, involved field RT to 55 (90%), and extended-field RT to 6 (10%) patients, respectively. Median radiation dose was 30 Gy (18–40 Gy). Results: All 25 patients with early-stage achieved complete response (CR) with CMT. At a median follow-up of 70 months (range 12–230 months), relapse was seen in two patients (1 local and 1 distant). Of 26 patients with advanced stage, 25 achieved a CR and 1 had stable disease with CMT. Relapse occurred in one patient (distant). In patients with early-stage treated with chemotherapy only ( n = 30, 24%), 9 patients had relapse (4 local and 5 distant) while in those with RT only ( n = 10, 8%), 4 developed distant relapse. In patients with advanced stage treated with chemotherapy only ( n = 34, 27%), 8 relapsed (5 local and distant, 3 distant only). Patients with relapse were salvaged with CMT ( n = 6), chemotherapy ( n = 15), or RT ( n = 3). Two patients have died. Five years' disease-free survival (DFS) in patients with early favorable stage, early unfavorable stage, and advanced stage was 91%, 82%, and 73%, respectively ( P = 0.026). DFS was significantly better with CMT than chemotherapy or radiation alone. Five years' overall survival (OS) was 93%, 92%, and 84%, respectively ( P = 0.139). Second malignancy occurred in 3 (2.4%) patients; carcinoma of the tongue, pseudomyxoma peritonei, and non-HL each, respectively. None of these patients had received prior radiation. Conclusion: CMT improved DFS in patients with HL. OS was similar in all patients irrespective of treatment combinations. The incidence of second malignancy was 2.4%

Ultrasonography guided fine needle aspiration cytology in patients with laryngo-hypopharyngeal lesions / Punção aspirativa por agulha fina guiada por ultrassonografia em pacientes com lesões laríngeo-hipofaríngeas

Abstract Introduction: Laryngeal lesions are usually evaluated by microlaryngoscopy/direct laryngoscopy under anaesthesia for disease mapping and tissue diagnosis. However patients with anticipated airway compromise due to laryngeal mass may require either a protective tracheotomy or emergency tracheotomy to secure the airway. To minimise risk of unplanned tracheotomy and expedite the diagnosis we performed ultrasound-guided transcutaneous fine needle aspiration cytology. Objective: To evaluate the feasibility and performance of ultrasound-guided transcutaneous fine needle aspiration cytology of suspicious/recurrent laryngo-hypopharyngeal masses. Methods: Fine needle aspiration cytology was performed under ultrasound guidance. Twenty- four patients were recruited, of which 17 had a pure laryngeal lesion; 6 patients had laryngo-pharyngeal, and one patient had a base tongue lesion with supra-glottis extension. Results: Out of 24 patients, 21 had positive cytology for squamous cell carcinoma, 2 patients had non-diagnostic cytology (atypical cells) and the other had inadequate tissue for definitive diagnosis. Patients with negative and inconclusive cytology underwent direct laryngoscopy biopsy, which was positive for squamous malignancy. All patients tolerated the procedure well and no adverse events were noted. Conclusion: Although direct laryngoscopy remains the standard of care in evaluation of laryngo-hypopharyngeal lesions, this pilot study has shown that ultrasound-guided transcutaneous fine needle aspiration cytology was feasible as an out-patient procedure, employing safe and sensitive technique enabling rapid diagnosis and avoiding the need for direct laryngoscopy under GA for tissue diagnosis.

Resumo Introdução: As lesões laríngeas são geralmente avaliadas por microlaringoscopia/laringoscopia direta sob anestesia para mapeamento da doença e diagnóstico tecidual. No entanto, em pacientes com comprometimento prévio das vias aéreas devido à lesão laríngea, pode ser necessária uma traqueostomia protetora ou traqueostomia de emergência para assegurar as vias aéreas. Para minimizar o risco de uma traqueostomia não planejada e facilitar o diagnóstico, realizamos punção aspirativa por agulha fina guiada por ultrassonografia transcutânea. Objetivo: Avaliar a viabilidade e o desempenho da punção aspirativa por agulha fina guiada por ultrassonografia transcutânea em lesões laríngeo-hipofaríngeas suspeitas/recorrentes. Método: A punção aspirativa por agulha fina foi realizada sob orientação ultrassonográfica. Foram recrutados 24 pacientes, 17 com lesão laríngea apenas, 6 com lesão laríngeo-faríngea e um com lesão na base da língua com extensão supraglótica. Resultados: Dos 24 pacientes, 21 apresentaram citologia positiva para carcinoma espinocelular, 2 citologia não diagnóstica (células atípicas) e o outro tecido inadequado para o diagnóstico definitivo. Os pacientes com citologia negativa e inconclusiva foram submetidos à biópsia através de laringoscopia direta, que foi positiva para lesão maligna espinocelular. Todos os pacientes toleraram bem o procedimento e nenhum evento adverso foi observado. Conclusão: Embora a laringoscopia direta continue a ser o padrão de cuidado na avaliação das lesões laríngeo-hipofaríngeas, este estudo piloto demonstrou que a punção aspirativa por agulha fina guiada por ultrassonografia transcutânea é uma técnica viável, ambulatorial, segura e sensível, permite rápido diagnóstico e evita a necessidade de laringoscopia direta sob anestesia geral para diagnóstico tecidual.

Role of narrow band imaging in the diagnosis of laryngeal lesions: Pilot study from India

INTRODUCTION: Narrow band imaging (NBI) is a new imaging technique developed to improve the diagnostic accuracy of head and neck cancers by depiction of tumor-specific neo-angiogenesis. The purpose of this study was to assess the value of NBI in the diagnosis of laryngeal lesions. AIM: To assess the sensitivity and specificity of combined white light endoscopy (WLE) and NBI compared with WLE alone in the diagnosis of laryngeal lesions. SETTINGS AND DESIGN: Prospective study. MATERIALS AND METHODS: Thirty consecutive patients with various laryngeal lesions scheduled for microlaryngoscopic evaluation underwent WLE followed by NBI. Endoscopic NBI findings were classified into five types (I–V) according to the intraepithelial papillary capillary loop features. Types I–IV are considered benign, whereas type V is considered malignant. The observations were compared with histopathology. STATISTICAL ANALYSIS: Sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy (i.e., invasive carcinoma and carcinoma in situ) by means of NBI with WLE were calculated. RESULTS: The sensitivity of WLE combined with NBI (100%) was higher than WLE alone (82.6%) in detecting laryngeal cancers. NBI helped in identifying four malignant lesions missed by WLE alone. Two children with respiratory papillomatosis also demonstrated type V pattern, a potential pitfall, leading to an overall positive predictive value of 92% and a negative predictive value of 100%. CONCLUSION: Combining NBI with WLE increases the sensitivity of detection of laryngeal cancer and its precursor lesions. NBI is also useful in some benign lesions as well as in post-radiotherapy patients.

Fas receptor (CD95) & Fas ligand (CD178) expression in patients with tobacco-related intraoral squamous cell carcinoma.

Background & objectives: Fas receptor and Fas Ligand (FasL) system has been implicated in the resistance to apoptosis, insensitivity to chemotherapy and in providing immune privileged status to most of the tumours. However, no reports are available on Fas and FasL expression in patients with tobacco-related oral carcinoma. Therefore, the present study was undertaken to observe Fas and FasL expression and their correlation with clinicopathological features as well as cell cycle parameters. Methods: Immunohistochemistry for Fas, FasL and DNA flow cytometry for cell cycle parameters was successfully done on 41 paraffin embedded tumour and 10 normal samples. The results were evaluated for possible association of Fas and FasL with clinicopathological features and cell cycle parameters. Results: Weak Fas expression was observed on the cell membrane only in 2 of 41 (5%) oral tumours while FasL immunoreactivity was seen in 26 of 41 (63.4%) tumours. In contrast, all ten normal oral tissues exhibited strong cytoplasmic and membrane Fas receptor immunoreactivity but absence of FasL staining. Older patients, greater tumour size and lymph node positivity were found to be associated with high expression of FasL. Significantly higher (P<0.01) expression of FasL was observed in oral tumours with aggressive DNA pattern like aneuploidy and high S-phase fraction. Interpretation & conclusions: Downregulation of Fas receptor and up-regulation of Fas ligand appear to be an important feature of tobacco-related intraoral carcinoma. Association of FasL expression with advanced clinical stage and aggressive DNA pattern suggests that the Fas and FasL system may be used as an important prognostic variable in patients with tobacco-related intraoral squamous cell carcinoma.

Correlation of cyclin D1 expression with aggressive DNA pattern in patients with tobacco-related intraoral squamous cell carcinoma.

Background & objectives: Cyclin D1 has been strongly implicated in cell proliferation particularly in the G1/S checkpoint of the cell cycle, and prognoses in human malignancies. We investigated the correlation between cyclin D1 overexpression and clinicopathological features as well as cell cycle parameters to understand its clinical significance in patients with tobacco-related oral squamous cell carcinoma (OSCC). Methods: Immunohistochemistry for cyclin D1 and DNA flowcytometry for cell cycle parameters was done on paraffin embedded tumour samples from 45 patients with OSCC Results: Higher expression of cyclin D1 was observed only in 30 (66.6%) of 45 cases that correlated with advanced age (P <0.02), higher tumour stage ((P<0.01), histological differentiation and lymph node metastasis (P <0.01). Analysis of nuclear DNA pattern revealed cyclin D1 immunoreactivity in tumours with aggressive DNA pattern such as aneuploidy ((P<0.05) and higher S phase fraction ((P<0.04). Interpretation & conclusions: Higher expression of cyclin D1 in oral cancer appears to be closely linked to cell proliferation, differentiation and lymph node invasion. Pre-operative evaluation of cyclin D1 in biopsy specimen may be useful in planning the most appropriate treatment strategies in patients with tobacco-related OSCC.

Does c-erbB-2 expression have a role in medulloblastoma prognosis?

The prognosis of patients with medulloblastoma has remained same for the last two decades. This study evaluated the role of c-erbB-2 expression in medulloblastoma as a prognostic marker. Fifty cases of medulloblastomas were investigated for the expression of c-erbB-2 protein using immunohistochemistry. The expression of c-erbB-2 was correlated with age, histology and disease-free survival (DFS). Thirty-five (70%) tumors were c-erbB-2 positive. Immunoreactivity for c-erbB-2 receptor was observed as mixed cytoplasmic and membrane positivity of tumour cells. The mean DFS in c-erbB-2 positive cases was 19.81 months compared to 48.33 months in c-erbB-2 negative cases. c-erbB-2 positivity was found to be an independent predictor of poor outcome in medulloblastoma (p value < 0.05). No correlation of c-erbB-2 expression was observed with the age of patient and the histological type of tumour. Additionally, c-erbB-4 expression was also evaluated in these tumours. Thirty-three cases showed co-expression of c-erbB-2 and c-erbB-4 proteins. However, c-erbB-4 expression alone was not associated with poor outcome, whereas its co-expression with c-erbB-2 was associated with shorter DFS (p < 0.05).

Breast cancer in males: a PGIMER experience.

AIM: Male breast cancer is a rare disease representing 1% of all breast cancers and less than 1% of all cancers in men. Because of its rarity, carcinoma breast has not been studied extensively and this prompted us to carry out this retrospective study. The aim of the study was to observe the clinical and pathological features, evaluate the prognostic factors and to co-relate the outcome in patients of male breast cancer. MATERIALS AND METHODS: Thirty patients of male breast cancer treated in the department of radiotherapy from year 1996-2000 were retrospectively analyzed. RESULTS: The actuarial five- year disease free survival was 40%. Three out of 30 i.e. 10% patients had loco-regional recurrence and all of them had locally advanced disease at presentation. Distant metastasis occurred in 9 patients of whom 6 patients had T3-T4 tumor and 1 patient had T1-T2 tumor. CONCLUSION: Modified radical mastectomy followed by external radiation therapy is the standard treatment for male breast cancer. Hormone therapy, as an adjuvant treatment, is the first line approach in a majority of patients and chemotherapy is reserved for patients with poor prognostic factors.

Comparative Evaluation of Concurrent Chemotherapy & Hyperfractionated radiotherapy Versus Conventional Radiotherapy alone in the Treatment of Locally Advanced Carcinoma Cervix-A Prospective Randomised Study

The aim of this study was to determine whether the addition of concurrent cisplalin and hyperfractionation in external pelvic radiotherapy improves local control and survival in patients with locally advanced carcinoma cervix as compared to treatment with conventional radiptjerapy alone. The morbidity of two treatment protocols was also compared. Sixty patients of newly diagnosed squamous cell carcinoma cervix, FIGO stage 118 and III were randomised into the following two treatment protocols: Group A (study group): Cisplatin30 mg/m2 weekly x 5 courses and external beam pelvic radiotherapy 50 Gy/33#4.5 weeks with hyperfractionation in first and following weeks. Group B (control group) : External beam pelvic radiotherapy 46 Gy/23#/4.5 weeks. Patients in both the group were then treated with intracavitary brachytherapy by LDR/MDR Selectron and a dose of 28 Gy was delivered to point A. The patients who were not suitable for intracavitary treatment were treated by supplementary external beam pelvic radiotherapy 20 Gy/ 10#/2" ceks. The actuarial local control at 4 years was 60% in group A and 42% in Group 8 9p<0.05). The a Cluarial disease free survival at 4 years was 52% in Group A and 35% in Group 8 (p<0.05). Only grade I acute and delayed haematological toxicity and grade I nausea and vomiting as acute toxicity "ere significantl) higher for Group A patients as compared to Group 8. Concomitant chemotherapy with hyperfraclionated radiotherapy is well tolerated and seems to offer potential benefit for imprOl ing the locoregional control in locally advanced carcinoma of cervix.