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Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward.

ABSTRACT: Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

SUBMITTER: Krug D

PROVIDER: S-EPMC7841378 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:The limited radiotherapy resources for global cancer control have resulted in increased interest in developing time- and cost-saving innovations to expand access to those resources. Hypofractionated regimens could minimize cost and increase access for limited-resource countries. In this investigation, we estimated the percentage cost-savings per radiotherapy course and increased radiotherapy access in African countries after adopting hypofractionation for breast and prostate radiotherapy. For perspective, results were compared with high-income countries. METHODS:The cost and course of breast and prostate radiotherapy for conventional and hypofractionated regimens in low-resource facilities were calculated using the Radiotherapy Cost Estimator tool developed by the International Atomic Energy Agency (IAEA) and then compared with another activity-based costing model. The potential maximum cost savings in each country over 7 years for breast and prostate radiotherapy were then estimated using cancer incidence data from the Global Cancer Observatory database with use rates applied. The increase in radiotherapy access was estimated by current national capacities from the IAEA directory. RESULTS:The estimated cost per course of conventional and hypofractionated regimens were US$2,232 and $1,339 for breast treatment, and $3,389 and $1,699 for prostate treatment, respectively. The projected potential maximum cost savings with full hypofractionation implementation were $1.1 billion and $606 million for breast and prostate treatment, respectively. The projected increase of radiotherapy access due to implementing hypofractionation varied between +0.3% to 25% and +0.4% to 36.0% for breast and prostate treatments, respectively. CONCLUSION:This investigation demonstrates that adopting hypofractionated regimens as standard treatment of breast and prostate cancers can result in substantial savings and increase radiotherapy access in developing countries. Given reduced delivery cost and treatment times, we anticipate a substantial increase in radiotherapy access with additional innovations that will allow progressive hypofractionation without compromising quality.

Project description:Background and purposeThe interplay effect of respiratory motion on the planned dose in free-breathing right-sided whole-breast irradiation (WBI) were studied by simulating hypofractionated VMAT treatment courses.Materials and methodsTen patients with phase-triggered 4D-CT images were included in the study. VMAT plans targeting the right breast were created retrospectively with moderately hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) and ultra-hypofractionated (26 Gy 5 fractions of 5.2 Gy) schemes. 3D-CRT plans were generated as a reference. All plans were divided into respiratory phase-specific plans and calculated in the corresponding phase images. Fraction-specific dose was formed by deforming and summing the phase-specific doses in the planning image for each fraction. The fraction-specific dose distributions were deformed and superimposed onto the planning image, forming the course-specific respiratory motion perturbed dose distribution. Planned and respiratory motion perturbed doses were compared and changes due to respiratory motion and choice of fractionation were evaluated.ResultsThe respiratory motion perturbed PTV coverage (V95%) decreased by 1.7% and the homogeneity index increased by 0.02 for VMAT techniques, compared to the planned values. Highest decrease in CTV coverage was 0.7%. The largest dose differences were located in the areas of steep dose gradients parallel to respiratory motion. The largest difference in DVH parameters between fractionation schemes was 0.4% of the prescribed dose. Clinically relevant changes to the doses of organs at risk were not observed. One patient was excluded from the analysis due to large respiratory amplitude.ConclusionRespiratory motion of less than 5 mm in magnitude did not result in clinically significant changes in the planned free-breathing WBI dose. The 5 mm margins were sufficient to account for the respiratory motion in terms of CTV dose homogeneity and coverage for VMAT techniques. Steep dose gradients near the PTV edges might decrease the CTV coverage. No clinical significance was found due to the choice of fractionation.

Project description:IntroductionThere has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.Methods and analysisThis is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.DiscussionThe trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.Ethics and disseminationThe trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.Trial registration numberRegistered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018.

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Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward.

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