Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin. Electronic address: .
International journal of radiation oncology, biology, physics (Impact Factor: 4.18). 08/2012; 84(4):973-82. DOI: 10.1016/j.ijrobp.2012.01.064
Source: PubMed

ABSTRACT To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer.
Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade ≥3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring ≥6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates.
At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity.
Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Surgery, radiotherapy, and chemotherapy are the mainstays of cervical cancer treatment. Many patients receive multiple treatment modalities, each with its own long-term effects. Given the high 5-year survival rate for cervical cancer patients, evaluation and improvement of long-term quality of life are essential. Pertinent articles were identified through searches of PubMed for literature published from 1993 to 2014. We summarize quality of life data from long-term follow-up studies of cervical cancer patients. We additionally summarize small group interviews of Hispanic and non-Hispanic cervical cancer survivors regarding social support and coping. Data are varied in terms of the long-term impact of treatment on quality of life, but consistent in suggesting that patients who receive radiotherapy as part of their treatment have the highest risk of increased long-term dysfunction of bladder and bowel, as well as sexual dysfunction and psychosocial consequences. Rigorous investigations regarding long-term consequences of treatment modalities are lacking. Continued work to improve treatment outcomes and survival should also include a focus on reducing adverse long-term side effects. Providing supportive care during treatment and evaluating the effects of supportive care can reduce the prevalence and magnitude of long-term sequelae of cervical cancer, which will in turn improve quality of life and quality of care. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.
    Clinical Therapeutics 01/2015; 37(1):39-48. DOI:10.1016/j.clinthera.2014.11.013 · 2.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy. Medical records of FIGO stage IIB cervical cancer patients treated between July 2008 and December 2011 were retrospectively reviewed. A total of 148 patients underwent radical hysterectomy with pelvic lymph node dissection followed by adjuvant radiotherapy (surgery-based group). These patients were compared with 290 patients that received radical radiotherapy alone (RT-based group). Recurrence rates, progression-free survival (PFS), overall survival (OS), local control rates, and treatment-related complications were compared for these two groups. Similar rates of recurrence (16.89% vs. 12.41%, p = 0.200), PFS (log-rank, p = 0.211), OS (log-rank, p = 0.347), and local control rates (log-rank, p = 0.668) were observed for the surgery-based group and the RT-based group, respectively. Moreover, the incidence of acute grade 3-4 gastrointestinal reactions and late grade 3-4 lower limb lymphedema were significantly higher for the surgery-based group versus the RT-based group. Cox multivariate analyses found no significant difference in survival outcome between the two groups, and tumor diameter and histopathology were identified as significant prognostic factors for OS. Radical radiotherapy was associated with fewer treatment-related complications and achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer compared to radical hysterectomy followed by postoperative radiotherapy.
    BMC Cancer 02/2014; 14(1):63. DOI:10.1186/1471-2407-14-63 · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m2, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m2/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.
    International journal of radiation oncology, biology, physics 11/2014; 90(4):778–785. DOI:10.1016/j.ijrobp.2014.07.033 · 4.18 Impact Factor