Aim : To analyze overall and progression-free survival after letrozole in postmenopausal women with advanced breast cancer who failed after tamoxifen therapy. Materials and Methods : This is a retrospective analysis of 95 patients with breast cancer who were postmenopausal and had failed after tamoxifen therapy. Dose of letrozole was 2.5 mg daily until disease progressed. Patients had estrogen receptor-and/or progesterone receptor-positive tumors or both receptors were unknown. One complete course of (6cycles) chemotherapy for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, time to treatment failure (TTF), overall survival and tolerability. Results : Median TTP was 10 months. ORR was 21% with complete response rate of 9%. Nine patients died of disease during treatment. Median overall survival was 36 months. Median time to response was three months and median duration of response was 13 months. Time to chemotherapy was 13.5 months and TTF was 9.3 months. Treatment failure was seen in 76% of patients. Disease progression was the main cause for treatment failure. Treatment was well-tolerated by all patients. Conclusion : This retrospective analysis shows that letrozole is quite effective as second line therapy in postmenopausal patients with advanced breast cancer who had failed after tamoxifen therapy.

Aims : To define the clinical and pathological predictors of locoregional recurrence (LRR) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NACT). Materials and Methods : We retrospectively reviewed the outcome of 141 patients with stage II to stage III carcinoma breast treated at Department of Radiotherapy, PGIMER, Chandigarh from 1998-2002. Mean age of the patients was 46 years, 49% of patients were premenopausal and 51% were postmenopausal. The tumor stage was T2 in 18%; T3 in 61% and T4 in 26% of the patients. NACT regimen given was FAC (5-fluorouracil, adriamycin and cyclophosphamide) in 85% and CMF (cyclophosphamide, methotrexate and 5-Fu) in 15% patients. Results : After NACT, surgery was possible in 95% patients. Conservative surgery was possible in 23% patients and mastectomy was done in 72% of patients. Pathological complete response (pCR) was seen in 18% patients and pathological partial response (pPR) in 69% of patients. Stable and progressive disease was seen in 6% and 7% of patients respectively. Adjuvant radiation therapy was given to 86% patients. Six percent patients developed progressive disease and 4% of patients did not turn up for radiation. Five year LRR was 6% and relapse free survival (RFS) was 94%. Thirty-two (23%) patients developed distant metastasis resulting in distant metastasis free survival of 77%. The factors that correlated positively with LRR on univariate analysis included tumor stage, stage and pathological nodal stage. However, on multivariate analysis, tumor stage and pathological nodal stage were significant. Factors that correlated for distant relapse were tumor stage, response to chemotherapy, type of surgery, extracapsular extension (ECE) and tamoxifen therapy. On multivariate analysis only ECE was the significant factor that correlated with distant relapse free survival. Conclusion : Thus, tumor stage and pathological nodal stage remains the most important predictor of LRR in LABC. Factors that correlated for distant relapse were tumor stage, response to chemotherapy, type of surgery and ECE and tamoxifen therapy.

Aim : The aim of our study was to compare the two standard treatment approaches in muscle invasive carcinoma of urinary bladder - radical cystectomy and chemo radiation. Materials and Methods : Transitional cell carcinoma (TCC) of bladder of stages, T2 to T4, N0/N1/N2 and MO were included in the study. Patients were allotted to two arms of the study. Arm A consisted of radical cystectomy. Adjuvant CMV chemotherapy was given for T3/T4 or Node positive disease only. Arm B received 2 cycles of neoadjuvant CMV chemo therapy followed by concurrent chemo radiation Results : Forty-four patients were recruited into the study. Thirty patients in the surgical arm and 13 patients in the chemo radiation arm. The actuarial two-year survival rate in surgical arm is 56% while in chemo radiation arm it is 54%. There was no statistically significant difference in disease-free survival also between the two groups. Conclusion : Chemo radiation yielded equivalent survival results with radical cystectomy. So it is worth giving preference to chemo radiation that will give a better quality of life for the patient.

In a search for antitumor agents, we carried out a screening of 4-arylcoumarins isolated from endophytic Streptomyces aureofaciens CMUAc130, by examining their possible inhibitory effect on the growth of s.c. transplanted Lewis lung carcinoma (LLC) in BDF-1 mice by intraperitoneal (i.p.) administration. The 4-arylcoumarins showed antitumor activity with T/C values of 80.8 and 50.0% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-p-methoxylphenylcoumarin treatment, respectively and 81.5 and 44.9% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-phenylcoumarin treatment, respectively, compared to adriamycin, which was used a positive control, with T/C value of 55.9% at 2 mg/kg. Furthermore, we investigated the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in A427, a human lung cancer cell lines. The cells were cultured in vitro for 24h in RPMI 1640 with 1.5% (v/v) ethanol, 100 µg/ml 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. Viability was determined by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cell cultured with 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. We conclude that 5,7-dimethoxy-4-phenylcoumarin is a more potent inhibitor of cell proliferation than 5,7-dimethoxy-4-p-methoxylphenylcoumarin and has more marked effects on oncoprotein expression.

Gardasil^® is the first quadrivalent human papillomavirus (HPV)- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

Radiation therapy is extensively used for treatment of malignancies, but angiosarcomas occurring in an irradiated area are uncommon. We report a rare case of high-grade epithelioid angiosarcoma of upper end of right humerus in a 67-year-old male occurring ten years following irradiation for giant cell tumor of the same anatomical site. The patient presented with progressive painful swelling over right shoulder and his X-ray showed erosion of medial cortex with lytic areas at upper end of humerus. He underwent excision of affected part of humerus followed by cemented hemiarthroplasty and bone grafting. After initial histopathological diagnostic dilemma the final report was given as post-radiation angiosarcoma. Disease recurred at the end of one-year follow-up period where upon he underwent wide resection with prosthesis replacement. He received four cycles of combination chemotherapy with doxorubicin and ifosfamide and currently is free of recurrence after six months follow -up.

Nasopharyngeal angiofibroma is a rare, highly vascular, benign, locally aggressive tumor, affecting boys of adolescent age. The aggressiveness and high vascularity makes surgery and even a biopsy difficult in majority of cases. Although surgery is the treatment of choice in early cases, considerable debate exists regarding the treatment of advanced disease with intracranial extension. Radiotherapy provides a good response and also avoids surgery-associated morbidity. We are herewith reporting a case of nasopharyngeal angiofibroma who showed complete hemostasis and improvement in vision to radiotherapy

Ependymoma are rare glial neoplasm, it rarely metastasize outside the central nervous system. We present a case of anaplastic ependymoma with extraneural metastases with review of literature. A ten-year-old male child presented with anaplastic ependymoma of choroid plexus and treated with craniospinal radiotherapy in 1998. He had intracranial recurrence in 2004, confirmed by biopsy. He was given adjuvant chemotherapy in form of PCV. At 10 months after completion of chemotherapy, he developed extracranial scalp metastasis and so was treated with palliative local radiation therapy to the scalp metastasis and systemic chemotherapy with oral Etoposide. Scalp metastasis completely disappeared and ataxia improved. After five cycles of chemotherapy, the patient had progression of disease in form of scalp and cervical lymph node metastasis confirmed by fine needle aspiration cytology, biopsy and immunohistochemistry. He was given salvage chemotherapy (carboplatin + ifosfamide + etoposide) at 3-weekly. He had partial response and was still on chemotherapy till May 2007.

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.

Dysphagia in an elderly patient necessitates urgent clinical evaluation to exclude the possibility of an underlying esophageal malignancy. Atherosclerotic aortic aneurysms are common in old age, but dysphagia aortica resulting from compression of the esophagus by an aortic aneurysm is a rare cause for dysphagia. Development of a malignant esophago-airway fistula can occur from a variety of tumors, the most common of which is esophageal cancer. A case of longstanding dysphagia resulting from dysphagia aortica later developing an esophageal malignancy complicated by esophago-bronchial fistula is outlined in this unique case report.

Aim : The aim of this retrospective study was to assess treatment outcomes for patients with locally advanced gynecological malignancies being treated with interstitial brachytherapy using Martinez universal perineal interstitial template (MUPIT) and to study the acute and late sequelae and survival after treatment by this technique. Materials and Methods : Ninety seven patients untreated with histopathological confirmation of carcinoma of cervix (37) vault (40) and vagina (20) were treated by combination of external beam RT (EBRT) using megavoltage irradiation to pelvis to dose of 4000-5000 cGy followed by interstitial brachytherapy using MUPIT between September 2001 to March 2005. Median age was 46 years. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitatory radiotherapy was found to be unlikely to encompass a proper dose distribution were treated by interstitial template brachytherapy using MUPIT application and were enrolled in this study. The dose of MUPIT was 1600-2400 cGy in 4-6# with 400 cGy /# and two fractions a day with minimum gap of six hours in between two fractions on micro-HDR. Criteria for inclusion of patients were as follows: Hb minimum 10 gm/dl, performance status - 70% or more (Karnofsy scale), histopathological confirmation FIGO stage IIB-IIIB (excluding frozen pelvis). Results : Among the 97 patients studied, 12 patients lost to follow-up and hence they were excluded from the study. Follow-up of rest of the patients was then done up to September 2006. The duration of follow-up was in the range of 20-60 months. Parameters studied were local control rate, complication rate, mortality rate and number of patients developing systemic metastasis. Local control was achieved in 56/85 (64.7%) and complication rate was 15/85 (17.6%). Local control was better for nonbulky tumors compared bulky tumors irrespective of stage of disease. Local control was better in patients with good regression of disease after external beam radiotherapy. Time of gap between EBRT and implant also had an impact on the outcome. Conclusion : Interstitial template brachytherapy by MUPIT is a good alternative to deliver high dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or likely to give optimal dose distribution. Loco regional control obtained is definitely better than EBRT alone and within the accepted range of complications.

Aim : To report the difference in the bladder and rectum doses with different applications by the radiotherapists in the same patient of the carcinoma of the uterine cervix treated by multiple fractions of high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Materials and Methods : Between January 2003 to December 2004, a total of 60 cases of the carcinoma uterine cervix were selected randomly for the retrospective analyses. All 60 cases were grouped in six groups according to the treating radiotherapist who did the HDR-ICBT application. Three radiotherapists were considered for this study, named A, B and C. Ten cases for each radiotherapist in whom all three applications were done by the same radiotherapist. And 10 cases for each radiotherapist with shared applications in the same patient (A+B, A+C and B+C). The bladder and rectal doses were calculated in reference to point "A" dose and were limited to 80% of prescribed point "A" dose, as per ICRU-38 recommendations. Received dose grouped in three groups- less then 80% (<80%), 80-100% and above 100% (>100%). A total of 180 applications for 60 patients were calculated for the above analyses. Results : There is a lot of difference in the bladder and rectal doses with the application by the different radiotherapists, even in the same patient with multiple fractions of HDR-ICBT. Applications by 'A' radiotherapist were within the limits in the self as well as in the shared groups more number of times, by 'B' radiotherapist was more times exceeding the limit and by 'C' radiotherapist doses were in between the A and B. Discussion and Conclusion : For the rectal and bladder doses most important factors are patient's age, disease stage, duration between EBRT and HDR-ICRT and patient anatomy, but these differences can be minimized to some extent by careful application, proper packing and proper fixation.

Purpose : This study was mainly framed to study the difference in tumor volumes as seen on computed tomography (CT) and magnetic resonance (MR) and their significance in planning. Materials and Methods : Twenty-five patients with brain tumor of different diagnoses who underwent stereotactic radiotherapy were included in this study. CT and MR imaging was done for all the patients with 2.5 mm slice thickness. The CT tumor volume and MR tumor volume were measured and compared with each other. The center of mass (CM) of the tumor volume delineated on CT and MR were computed and the shift between the two CMs was determined. Results : The mean and median volume of the tumor as measured from MR scans was 19.67 cc ± 13.73 and 16.13 cc (range: 3.25 cc - 50.37 cc). Similarly, the mean and median volume of the tumor as measured from CT scans was 15.05 cc ± 10.13 and 11.63 cc (range: 3.0 cc - 36.25 cc) respectively. The mean and median CM shift between CT and MR was 5.47 mm and 5.21 mm respectively. Conclusion : The study demonstrates that MR is an indispensable imaging modality in radiotherapy for planning brain tumors.

Chromosomal analysis was carried out in bone marrow sample of an 11-year-old girl suspected of myeloproliferative disorder. Conventional G-banding study detected a complex three-way translocation involving 7, 9 and 22, which has resulted in the formation of a variant Philadelphia chromosome causing rearrangement of abl and bcr genes in 87% cells. Fluorescence in situ hybridization (FISH) confirmed the fusion of bcr-abl oncogene. Thus the bone marrow karyotype was observed as 46,XX (13%) / 46,XX,t(7;9;22)(q11;q34;q11) (87%). Hyperdiploidy was present in two cells. In this study, both conventional cytogenetic and FISH diagnosis proved to be significant to identify the variant nature of the Philadelphia chromosome and hyperdiploid condition for introduction of a suitable treatment regimen and estimation of life expectancy of the young girl.

Background : Oral cancer (OC) mortality is very high in Sudan, particularly among men due to the habit of Toombak use (tobacco specific nitrose amine (TSN)) rich tobacco. Aims : Our aim was to determine whether OC is gender-specific due to increased Toombak use among males as suggested a risk for subsequent development of oral cancer. Settings and Design : We conducted a descriptive study of OC in Khartoum and obtained information on Toombak use, confounding variables for 39 incident patients with oral cancerous lesions and 43 hospital-based cases without apparent oral lesions. Materials and Methods : OC was affirmed by histopathology for all patients with oral lesions, hence oral epithelial atypia and leukoplakias were detected using cytology. Statistical Analysis : Data analyzed using a computer SPSS program. Results and Conclusions : Of the 82 subjects, there were 57 (70%) Toombak users and 25 (30%) non-tobacco users. Among the 39 patients with OC, 24 (61.5%) were Toombak users and 15 (38.5%) were non-tobacco users. Among 43 with atypical changes, 10 (23.3%) were non-tobacco users and 33 (76.7%) were Toombak users. Regarding gender, only 11 (13.4%) were females, of whom 8 (72.7%) were non-tobacco users. We conclude that oral cancer, atypia and leukoplakia were high among males who were Toombak users. In view of the high incidence (29%) of OC due to Toombak use, we propose the implementation of oral screening programme restricted to Toombak users.