Image Guided Intensity Modulated Radiation Therapy Shows Reduced Toxicity in Cervical Cancer

Image-guided intensity modulated radiation therapy (IG-IMRT) caused less toxicity compared to three-dimensional conformational radiation therapy (3D-CRT) with no difference in disease outcome in patients with cervical cancer undergoing postoperative radiotherapy, according to the results of the phase 3 PARCER trial (NCT01279135) published in the Journal of Clinical Oncology.

At a median follow-up of 46 months (interquartile range, 20-72), fewer primary endpoint events were seen in the IG-IMRT arm vs. the 3D-CRT arm, at 29 vs. 54, respectively. The 3-year cumulative incidence of late grade 2 or greater gastrointestinal (GI) toxicities in the IG-IMRT and 3D-CRT arms was 21.1% (95% CI, 14.7% at 29, 7%) versus 42.4% (95% CI, 33.7). % -52.3%), respectively (RR: 0.46; 95% CI: 0.29-0.73; P <.001>

“The results of the PARCER trial in patients with cervical cancer suggest that postoperative IG-IMRT results in a lower rate of late toxicity than conventional 3D-CRT, with no difference in efficacy, and should be the preferred radiotherapy technique in this patient. population, ”wrote lead study author Supriya Chopra, MD, of the Tata Memorial Center, and co-authors in the study publication.

Adjuvant postoperative radiation therapy (PORT) reduces the risk of recurrence in patients with early cervical cancer with intermediate risk characteristics and improves survival in patients with high risk characteristics, but is also associated with long-term gastrointestinal toxicity.

Newer approaches like IG-IMRT can reduce the radiation dose to the gut. In addition, phase 2 studies showed reduced acute gastrointestinal toxicity with IMRT, and a randomized phase 3 study showed improved short-term patient-reported outcomes with IMRT compared with IMRT. conventional radiotherapy.

However, it is not clear whether IMRT leads to reduced late gastrointestinal toxicity compared to 3D-CRT.

To better understand the burden of late symptoms of IG-IMRT versus 3D-CRT, patients were randomized to receive IG-IMRT or 3D-CRT and stratified by type of hysterectomy and use of concomitant chemotherapy.

Eligible patients included women with cervical cancer who had an indication for PORT.

The primary endpoint was grade 2 or greater late gastrointestinal toxicity over 3 years, assessed using Common Toxicity Criteria for Adverse Events v3.0 and estimated using an analysis in intention to treat time to event, with a study-level Type I error of 0.05 and a nominal of 0.047 after accounting for an interim analysis.

Secondary endpoints included acute toxicity, health-related quality of life (QOL), pelvic recurrence-free survival (PRFS), disease-free survival (DFS), and overall survival (OS).

Follow-up was every 3 months for the first 2 years, once every 6 months for the next 3 years, and annually thereafter.

Between January 2011 and November 2019, 300 patients were randomized to receive IG-IMRT (n = 151) or 3D-CRT (n = 149).

Additional results showed lower or higher grade 2 late gastrointestinal toxicity with IG-IMRT compared to 3D-CRT across stratification factors in subgroup analyzes.

The cumulative incidence of any late toxicity grade 2 or greater was 28.1% (95% CI, 20.7% -37.4%) vs. 48.9% (95% CI, 40% to 58 , 7%), respectively (HR, 0.50; 95% CI, 0.33-0.76; P <.001>

The use of IG-IMRT was associated with a tendency to reduce acute diarrhea grade 2 or greater (17.2% vs. 26.1%, respectively; P = .06) with no difference in overall acute gastrointestinal toxicity grade 2 or greater (29.8% vs. 28.8%, respectively; P = .38).

Univariate analysis revealed that absence of acute grade 2 or greater diarrhea, absence of grade 2 or greater acute gastrointestinal toxicity, large intestinal volume receiving 40 Gy at less than 90 cc, and use IG-IMRT were significantly associated with a lower incidence of grade 2 or greater late gastrointestinal toxicity. Multivariate analysis indicated that only IG-IMRT was associated with grade 2 lower or higher late gastrointestinal toxicity (RR: 0.53; 95% CI: 0.32-0.86; P = .01).

Additionally, in the IG-IMRT and 3D-CRT arms, respectively, there were 30 and 25 PRFS events, 31 and 29 DFS events, and 29 and 23 OS events.

The 3-year PRFS rate was 81.8% (95% CI, 73.5% -87.7%) versus 84% ​​(95% CI, 76.0% to 89.5%), respectively (RR: 1.17; 95% CI, 0.68-1.99; P = 0.55). The rate of SSM at 3 years was 76.9% (95% CI, 68.4% to 83.4%) versus 81.2% (95% CI, 72.9% to 87.2%) , respectively (RR: 1.03; 95% CI, 0.62-1.71; P = .89). The rate of OS at 3 years was 82.9% (95% CI, 74.6% -88.6%) versus 89.2% (95% CI, 82.1% to 93.6%) , respectively (RR: 1.23; 95% CI, 0.71 to 2.14; P = .44). No difference was observed in PRFS, DFS and OS at 3 and 5 years.

Regarding the quality of life, after the end of treatment, as well as at months 12, 36 and 60, 289, 250, 147 and 83 patients were eligible for the assessment of the quality of life. Most questionnaires were returned at all times: 89.2% (n = 258/289), 86.8% (n = 217/250), 83.6% (n = 123/147) and 73, 5% (n = 60/83), respectively.

Long-term follow-up indicated that patients in the IG-IMRT arm had improved functional scores and lower symptom scores. A significant increase was observed in the overall health score (β = 3.17; P = .01) in the IG-IMRT arm. Patients who received IG-IMRT improved their physical functioning (β = 3.52; P = .042), role functioning (β = 4.46; P = 0.024) and emotional functioning (β = 5.46; P = .02) compared to patients who received 3D-CRT.

Additionally, lower symptom scores have been reported in patients treated with IG-IMRT. Patients who received IG-IMRT had less fatigue (β = –6.89; P = 0.004), loss of appetite (β = –7.08; P = 0.008), diarrhea (β = –3.90; P = 0.048) and intestinal symptoms (β = –4.51; P = 0.002) during tracking. However, the quality of life scores did not differ significantly when the time per treatment arm interaction was performed.

Numerically, fewer patients in the IG-IMRT arm reported moderate to severe diarrhea (1.6% vs. 3.8%), abdominal cramps (1.7% vs. 9.1%), and difficulty controlling intestine (5.1% vs. 14.9%) at 36 months. More patients in the 3D-CRT arm continued to report symptoms.

“Although no significant difference was observed between the two arms for any area of ​​quality of life over time by the interaction analyzes of the treatment arm, it should be noted that a higher proportion of patients in the 3D-CRT arm continues to report symptoms after extended 60% follow-up. months, ”the study authors concluded.


  1. Chopra S, Gupta S, Kannan S, et al. Late toxicity after adjuvant conventional irradiation versus image-guided intensity modulated radiotherapy for cervical cancer (PARCER): a randomized controlled trial. J Clin Oncol. 2021; 39 (33): 3682-3692. doi: 10.1200 / JCO.20.02530

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