Concomitant radiation therapy and chemotherapy in cancer cervix: results using high dose rate brachytherapy

The use of concomitant radiation and chemotherapy in the management of carcinoma of the cervix improved the overall and disease free rates for patients with carcinoma of the cervix and this combined modality is considered now the standard of care in many oncology centres. The aim of the current study was to assess the treatment results [mainly response rate and disease free survival] for patients with cancer cervix treated with concomitant chemoradiation therapy using high dose rate brachytherapy after external beam radiation therapy. This is a prospective phase II study done in patients with carcinoma of cervix referred for concomitant radiation and chemotherapy. Patients were treated with external beam radiation therapy [EBRT] given as 4500cGy/25 fractions/5 weeks [180cGy per fraction] using linear accelerator with 18M v photons, followed after one week with high dose rate brachytherapy using iridium 192 giving a dose of 600cGy to point A as once weekly outpatient session for four consecutive weeks [so the total dose of brachythrapy given was 2400cGy]. Meanwhile; a concomitant chemotherapy with cisplatinum was given as a radiosensetizer during EBRT at a weekly intravenous [IV] infusion of 40mg/m[2]. Assessment of response rate to treatment was done clinically as well as by magnetic resonance imaging [MRI] at 6 weeks after the end of treatment, and then a regular follow up at 3 monthly intervals was done. At the end of follow up; assessment of disease free survival [DFS] was done. A correlation between different prognostic variables [like histopatho-logical grade, stage, initial response to treatment] and DFS was done. Twenty four patients with carcinoma of the cervix were included in the study. Their mean age was 51.6 years [ +/- 15.5 years SD; standard deviation]. All patients had squamous cell carcinoma; 54.2% had grade [G] II, 33.3% had GIII, and the least was GI [12.5%]. Staging was done according to FIGO [Federation Internationale de Gynecologic et d'Obstetrique] system [appendix I]; and the results showed stage IA 12.5%, IB 4.2%, IIA 16.7%, IIB 25%, IIIA 8.3%, and stage IIIB as 20.8% stage IVA 12.5%. Sequelae of treatment were assessed by Radiation Therapy Oncology Group [RTOG] toxicity criteria [appendix 2], whereby diarrhea GII was seen in 12.5%, GII cystitis in 21% and GII neutropenia in 8.3%. Initial post treatment response showed 50% complete remission [CR], 25% partial response [PR], 8.3% stable disease [SD], and 16.7% disease progression [DP]. After a mean follow up period of 26 months [SD 9.7 months] [range 10-40 months], the mean DFS was 27.29 months [standard error SE 1.93], and [95% confidence interval 9CI]: 23.52-31.07]. The median DFS was 29 months [SE 3.06], [95% CI, 23-35 months]. The 2 year DFS for the whole group was 60% and the 3 year DFS was 27%. Correlation of different prognostic variables with response rate revealed that: The histopathological grade of the tumour had a borderline significance [p value 0.057] with better response in GI, and GII as compared to GIII. FIGO stage did not influence response to treatment [p value 0.59]. There was no correlation between DFS and histopathological grade [p value 0.53]; FIGO stage [p value 0.66]; although there was a difference in DFS between different stages [in stage I the 3 years DFS rate was 90% as compared to stage IVA where the 3 years DFS rate was only 10%] however it was statistically not significant. Also no correlation was found between DFS and response to treatment [p value 0.88]. On multivariate analysis none of the prognostic variables mentioned [histopathological grade, FIGO stage, initial response to treatment] influenced DFS. The use of external beam radiation therapy concomitant with systemic chemotherapy [cisplatinum], and followed by high dose rate brachytherapy is an acceptable treatment modality for carcinoma of the cervix with mild treatment related toxicity

Hypofractionated radiation therapy versus conventional radiation in they adjuvant setting of breast cancer; is there any difference in toxicity?

Recent studies of radiation toxicity in the treatment of breast cancer have shown that; the effects on normal tissues can constitute a significant health problem. One of these problems is skin toxicity. The aim of the current study is to compare the acute skin toxicity between two different fractionation schedules of adjuvant breast radiation: the conventional radiation [CFR] versus hypofractionated radiation [HFR]. This is a prospective randomized study done in breast cancer patients referred for adjuvant radiation therapy. Radiation therapy was given in either one of two ways: CFR [5000 cGy/ 25 fractions I 5 weeks; 200 cGy per fraction] or HFR [4005 cGy/15 fractions / 3 weeks; 267 cGy per fraction] Acute radiation reactions were graded according to the Radiation Therapy Oncology Group toxicity grading system [RTOG] [1]. A comparison was done between the incidence of these reactions and different variables as: total radiation dose, type of surgery, number of surgically dissected nodes.etc. Seventy eight patients were accrued to the study, of whom 57.7% had breast conservative surgery [BCS], while 42.3% had modified radical mastectomy [MRM]. Patients who had received HFR represented 53.8%, while those who received CFR represented 46.2% of all patients. The majority of patients [64.1%] had grade 0/II radiation reaction, and 35.9% had grade III/IV reaction. On univariate analysis, there was a statistically significant difference between the two radiation arms regarding the incidence of radiation reaction, with higher incidence [52.8%] in CFR as compared to 21.4% in HFR [p 0.004], while the other variables [type of surgery, number of surgically removed nodes, etc] were not statistically significant. On multivariate analysis; the only factor of statistical significance regarding the incidence of radiation reaction was the radiation therapy schedule, with a higher incidence in CFR [p value 0.03]. There is a statistically less incidence of acute radiation reactions in hypofractionated arm as compared to conventional fractionated arm in the adjuvant radiation of breast cancer.

Neoadjuvant chemotherapy for locally advanced breast cancer; impact on reponse rate

This is a prospective phase II study done in locally advanced breast cancer patients with the aim of assessment of clinical and pathological response rate after neoadjuvant chemotherapy and time to disease progression. Thirty patients with locally and advanced breast cancer were included in the study. All eligible patients were given neoadjuvant chemotherapy as two cycles of Doxorubicin and Cyclophosphamide [AC], then two cycles of Docetaxel, and Cisplatinum [DP]. Post-treatment clinical and radiological assessment was done, whereby those patients who achieved complete remission [CR] or partial remission [PR] were referred for mastectomy, while those who progressed on neoadjuvant chemotherapy were excluded from the study. Pathological evaluation of mastectomy specimens was done for all patients to assess the pathological response rate. The results showed that 30 patients of locally advanced [stage IIIA and IIIB] breast cancer were included in this study. Twenty-seven patients [90%] showed complete clinical and radiological remission [CR]; while, three cases [10%] showed partial clinical and radiological remission [PR]. Regarding pathological response three cases [10%] showed complete pathologic response, while the rest of cases [90%] showed residual disease. There was no correlation between clinical and pathological response rates. Treatment related toxicities were nausea GI-II in 14 cases [47%], vomiting GI-II in 10 cases [33%], alopecia GII-III in all patients [100%], neutropenia GII in 11 cases [37%]. Docetaxel related toxicity was seen as allergic reaction in two cases [7%], mild peripheral neuropathy was seen in six cases [20%], No life threatening complications and no toxic deaths were observed. After a median follow up of 12 months, two cases out of 14 [14%] showed relapse [14%] and at the end of the study three cases out of total 30 [10%] relapsed

Advanced low grade non hodgkin's lymphoma [LGL]; treatment results using cyclophosphamide, fludarabine, and prednisone [CFP]

Fludarabine has been shown to be an effective agent in the treatment of low grade lymphoma; either used alone or in combination with other chemotherapeutic agents. It maintains its efficacy both for newly diagnosed cases as well as for patients with recurrent progressive low grade Non Hodgkin's Lymphoma [RPLGL]. This an open phase II study of CFP chemotherapy regimen conducted in patients with advanced LGL to explore the efficacy of this regimen and its toxicity profile. Between January 1998 and March 2000 41 patients aged 42-69 years [median 54] were enrolled to this multicenter study. All of the 37 evaluable patients, were allocated to receive 6 cycles of cyclophosphamide 300 mg/m[2] intravenously [IV.] day 1-3[DI-3], Fludarabine 25 mg/m[2] I.V.D 1-3 and prednisone 40 mg/m[2] PO, Dl-5. Chemotherapy cycles were repeated every 28 days for 6 cycles. Of the 37 evaluable patients. 20 patients [54%] had recurrent progressive disease [RPLQL], while 17 patients [46%] were newly diagnosed advanced LGL [stage; II bulky. III, and IV]. Clinical response to treatment was evaluated immediately after the completion of the chemotherapy schema, and defined according to categories; complete remission [CR], partial remission [PR]. The overall response rate for the whole group was 86% [32/37 patients]. Eleven patients [3 0%] achieved CR, and 21 patients [56%] achieved PR. Patients with newly diagnosed LGL had better