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

ABSTRACT

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