Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

Dose-volume correlation of cumulative vaginal doses and late toxicity after adjuvant external radiation and brachytherapy for cervical cancer.

PURPOSE: To investigate dose-response relationship between vaginal doses and long-term morbidity. METHODS AND MATERIALS: Patients receiving adjuvant pelvic (chemo) radiation and brachytherapy for cervical cancer from January 2011 to December 2014 were included. Baseline vaginal length was determined clinically and from imaging at BT planning. Dose points were defined along mucosa and at 5 mm depth at 12, 3, 6, and 9 'o' clock positions at every 2 cm from apex to introitus. Cumulative equivalent doses in 2 Gy were calculated. Vaginal stenosis was reported in reference to baseline length according to CTCAE version 3.0. Receiver operator characteristics curve was used to identify dose thresholds for univariate and multivariate analysis. RESULTS: Overall, 78 women with median age of 49 (32-71) years were included. The median dose at vaginal apex mucosa and 5 mm depth was 118 Gy3 (78-198) and 81 Gy3 (70-149) respectively. At median follow-up of 36 (18-60) months, vaginal stenosis ≥25%, and grade ≥ II telangiectasia was observed in 33.3% and 45.7%, respectively. On receiver operator characteristics analysis, apical mucosal dose >142 Gy3 and recto-vaginal point dose >86 Gy3 predicted for stenosis on univariate (p = 0.02, p = 0.06) and multivariate analysis (p = 0.04). The probability of stenosis increased from 32% at 70 Gy3, 38% at 80 Gy3, and 45% at 90 Gy3 rectovaginal point dose. No correlation was observed between vaginal doses and telangiectasia and vaginal stenosis and sexual quality of life. CONCLUSION: Vaginal apex mucosal dose >142 Gy3 independently predicts for vaginal stenosis.