Adaptive Intensity-Modulated Radiation Therapy Strategy May Ensure Adequate Target Coverage in Patients With Cervical Cancer
A novel, dosimetry-triggered, adaptive intensity-modulated radiation therapy strategy for patients with cervical cancer may minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion, according to a study by Lim et al in the International Journal of Radiation Oncology • Biology • Physics.
The adoption of small-margin intensity-modulated radiation therapy to treat cervical malignancies has been hampered by the highly variable nature of uterine motion and other aspects. These variables differ from one patient to another.
Ultimately, the consequences of these variables can result in target underdosing and higher-than-expected dosing to adjacent normal tissue. A possible solution to this problem is the implementation of protocols utilizing planning target volume margins that more accurately target tumors and limit the potential for unwarranted radiation exposure to normal tissue.
Although this type of approach may reduce the risk of target underdosing, the workload associated with its implementation on an individual basis is not clinically feasible. Thus, Lim and colleagues aimed to evaluate two different methods for implementing adaptive radiotherapy for patients with cervical cancer.
Study Details and Results
The investigators compared two methodologies of radiotherapy for cervical cancer: (1) creation of a midtreatment single replan for each patient to correct minor target underdosing and to reduce normal tissue dosing and (2) implementation of a selective replanning methodology for radiotherapy that is triggered by dosimetrically significant anatomic changes observed using magnetic resonance imaging. The second method would only be implemented in patients who at the time of treatment would likely benefit the most.
Data from 30 women with stage IB to IVA cervical cancer were analyzed. All patients received 45 to 50 Gy of whole-pelvis external-beam radiotherapy in 1.8- to 2-Gy fractions over 5 weeks. Clinical target volumes were separated into primary and nodal clinical target volumes.
Both of the replanning strategies improved the accumulated target dosimetry compared with no replanning. Clinically relevant gross tumor volume and/or primary clinical target volume dose thresholds failed for eight patients (27%). Among these eight patients, coverage failed for five patients within the anterior aspect of the target, three patients within the posterior aspect, three patients within the superior aspect, and one patient within the inferior aspect (multiple target locations failed in three patients). Pretreatment bladder and rectum volumes were not statistically different between the two groups of patients.
Regarding the need among these patients for replanning, 16 patients (53%) triggered at least one replan in the dosimetric adaptive intensity-modulated radiation therapy scenario: 11 (37%), 3 (10%), and 2 patients (7%) triggered 1, 2, and 3 replans, respectively, for a total of 23 replans. Most replans occurred early in treatment, when dosimetric errors have the greatest cumulative impact. It should be noted that patients with a larger pretreatment primary clinical target volume triggered fewer replans in the dosimetric adaptive intensity-modulated radiation therapy scenario.
Less Replanning With the Dosimetric vs Anatomic Approach
Compared with the anatomic adaptive intensity-modulated radiation therapy approach, the dosimetric adaptive intensity-modulated radiation therapy strategy reduced the total number of replans by 23% (from 30 to 23) while improving target coverage across the patient cohort. Even with a 3-mm margin, 73% of patients would have met dosimetric target objectives at treatment completion without any replanning interventions. The findings of this study suggest that the benefit of adaptive approaches may be primarily to ensure clinically acceptable target coverage in the context of these small margins.
Clinical Implications and Closing Thoughts
The data culled from this study suggest a new and practical adaptive radiotherapy methodology for patients with cervical cancer. This approach may ultimately drive a paradigm shift that leads to improved clinical outcomes.
The investigators remarked, “The study highlights the clinical importance of target and [organs at risk] motion in patients with cervical cancer and the dosimetric impact of this motion and proposes a new and practical adaptive method for ensuring robust target coverage in the context of workload and cost considerations.”
Michael Milosevic, MD, FRCPC, of the Princess Margaret Cancer Centre, Toronto, Ontario, Canada,is the corresponding author of the article in the International Journal of Radiation Oncology • Biology • Physics.
This work was supported by RaySearch Laboratories AB, the Canadian Institutes of Health Research Strategic Fellowship in the Excellence in Radiation Research for the 21st Century Program, the Giovanni and Concetta Guglietti Family Trust, the National Sciences and Engineering Research Council of Canada, and the Ontario Consortium for Adaptive Interventions in Radiation Oncology.
Anna Lundin, MSc, Henrik Rehbinder, PhD, and Johan Löf, PhD, are employees and shareholders of RaySearch Laboratories AB. David A. Jaffray, PhD, Joanne Moseley, BMath, and Kristy K. Brock, PhD, have a commercial licensing agreement with RaySearch Laboratories AB.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
