From the Journals

Moderate hypofractionation preferred in new guideline for localized PC



Moderate hypofractionation is preferred over conventional fractionation in treatment of patients with localized prostate cancer who are candidates for external beam radiotherapy (EBRT), according to new a clinical practice guideline.

A meta-analysis of randomized clinical trials showed that moderate fractionation delivered the same efficacy as did conventional fractionation with a mild increase in gastrointestinal toxicity, reported lead author Scott C. Morgan, MD of OSF Medical Group in Bloomington, Illinois, and his colleagues. The drawback of toxicity is outweighed by distinct advantages in resource utilization and patient convenience, which make moderate hypofractionation the winning choice.

For many types of cancer, a shift toward fewer fractions of higher radiation is ongoing, driven largely by technological advances in radiation planning and delivery.

“Technical advances have permitted more precise and conformal delivery of escalated doses of radiation to the prostate, thereby improving the therapeutic ratio,” the authors wrote in the Journal of Clinical Oncology.

Fractionation is typically limited by adjacent tissue sensitivity, but prostate tumors are more sensitive to radiation than the rectum, allowing for higher doses of radiation without damaging healthy tissue. While conventional fractionation doses are between 180 and 200 cGy, moderate hypofractionation delivers doses of 240-340 cGy. Ultrahypofractionation is defined by doses equal to or greater than 500 cGy (the upper limit of the linear-quadratic model of cell survival).

The present guideline was developed through a 2-year, collaborative effort between the American Society of Radiation Oncology, the Society of Clinical Oncology, and the American Urological Association. Task force members included urologic surgeons and oncologists, medical physicists, and radiation oncologists from academic and nonacademic settings. A patient representative and radiation oncology resident also were involved. After completing a systematic literature review, the team developed recommendations with varying degrees of strength. Supporting evidence quality and level of consensus also were described.

Of note, the guideline calls for moderate hypofractionation for patients with localized prostate cancer regardless of urinary function, anatomy, comorbidity, or age, with or without radiation to the seminal vesicles. Along with this recommendation, clinicians should discuss with patients the small increased risk of acute gastrointestinal toxicity, compared with conventional fractionation and the limited follow-up time in most relevant clinical trials (often less than 5 years).

The guideline conveyed more skepticism regarding ultrahypofractionation because of a lack of supporting evidence and comparative trials. As such, the authors conditionally recommended ultrahypofractionation for low-risk and intermediate patients, the latter of whom should be encouraged to enter clinical trials.

“The conditional recommendations regarding ultrahypofractionation underscore the importance of shared decision making between clinicians and patients in this setting,” the authors wrote. “The decision to use ultrahypofractionated EBRT at this time should follow a detailed discussion of the existing uncertainties in the risk-benefit balance associated with this treatment approach and should be informed at all stages by the patient’s values and preferences.”

The authors reported financial affiliations with Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others.

SOURCE: Morgan et al. J Clin Oncol. 2018 Oct 11. doi: 10.1200/JCO.18.01097.

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