Severe late toxicities following concomitant chemoradiotherapy compared to radiotherapy alone in cervical cancer: an inter-era analysis.
OBJECTIVE
To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792, USA. gondi@humonc.wisc.edu
Vinai
V
Gondi
Søren M
SM
Bentzen
Kathryn L
KL
Sklenar
Emily F
EF
Dunn
Daniel G
DG
Petereit
Scott P
SP
Tannehill
Margaret
M
Straub
Kristin A
KA
Bradley
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D016001:Confidence Intervals; D003251:Constriction, Pathologic / Q000628:therapy; D004106:Dilatation / Q000295:instrumentation; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D010384:Pelvic Bones / Q000293:injuries / Q000528:radiation effects*; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D001743:Urinary Bladder / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D014621:Vagina / Q000473:pathology / Q000528:radiation effects*
D000970:Antineoplastic Agents; D002945:Cisplatin