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Intensity-Modulated Radiotherapy As Primary Treatment For Prostate Cancer: Acute Toxicity In 114 Patients

Reviewer: Charles E Stewart, MD PhD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 18 de noviembre del 2005

Authors: G D e M eerleer , L V akaet , S M eersschout , et al.
Source: Int. J. Radiation Oncology Biol. Phys ., 60 (2004) 777-787 .

Background

In the setting of external beam radiotherapy treatment of prostate cancer, Intensity Modulated Radiotherapy (IMRT) is rapidly becoming the norm and has replaced standard 3-dimesional conformal treatment in the majority of academic- and community-based centers. Inherent in substantial changes to radiation delivery techniques are not only potential changes in tumor control probabilities, but also potential changes in both acute and long-term side effects. The intent of this study was to examine acute toxicities of IMRT in patients with low, intermediate, and high risk for extra-prostatic disease. This study follows on the heels of a more comprehensive study by Zelefsky et al . (Int. J. Radiation Oncology Biol. Phys., Vol. 53, No. 5, pp. 1111–1116, 2002) that examined early toxicity in a larger patient cohort with extensive follow-up and more cleanly-parsed data.

Methods

• 114 patients with localized or locally advanced prostate cancer (T1-4, N0M0), ages 41-81, PSA from 0.01-150 ng/ml were stratified and treated based on the Bolla criteria (Bolla et al. N Engl J Med 1997;337:295–300.)
• The patient population could be fragmented into the following demographics: T1 disease (29%), T2 disease (44%), T3 disease (24%), T4 disease (4%); PSA < 10 (39%), 10 ≤ PSA< 20 (39%), PSA ≥ 20 (23%); and Gleason score (GS) 2-5 (35%), GS 6 (28%), GS 7 (20), 8-10 (17%)
• Patients with intermediate and poor prognostic factors received 6 month and 3 year hormonal therapy, respectively, starting 3 months before the first RT dose. The hormonal therapy was preceded by 4 weeks of anti-androgen therapy
• CTV (clinical target volume) was defined as the prostate and seminal vesicles; PTV (planning target volume) consisted of a 1-cm cranial-caudal expansion of the CTV and 7 mm circumferential expansion; daily localization of the target by either ultrasound or fiducial markers was NOT performed
• Median PTV dose in the good prognosis group was 74 Gy, in the intermediate prognosis group was 72 or 74 Gy, and in the poor prognosis group 76 or 78 Gy. After 50 Gy, the seminal vesicles were excluded from the PTV if the predicted seminal-vesicle involvement was less than 10% by the Roach formula
• A three-field IMRT technique using 18 MV photons in a step-and-shoot technique from 0, 116, and 244 degrees was employed
• Follow-up data on morbidity from one and three months post-treatment is presented

Results and Conclusions

• Data from one and three month follow-up reveals nearly 90% of patients had Grade 0 gastrointestinal and genitourinary toxicities; there was an increase in GI toxicity at three months while the majority of genitourinary toxicities had resolved
• Summated dose-volume histograms from the entire patient population treated to different dose levels for PTV and CTV coverage are presented; because patients were treated to different final doses, this data is confounded and uninterpretable

Discussion

The description of acute toxicity after IMRT for prostate cancer has been previously well characterized by Zelefsky et al . as described above, and remains the standard by which other articles should be compared. Their study involved 772 patients followed for over 4 years, and also measured initial biochemical failure rates. In addition, studies of IMRT for prostate cancer without daily localization of the prostate (such as the one summarized here) become uninterpretable. Numerous groups ( eg. Bentel et al , Int. J. Radiation Oncology Biol. Phys., Vol. 47, No. 1, pp. 247–253, 2000) have demonstrated considerable daily motion of the prostate independent of bony landmarks. Furthermore, the 7mm circumferential margin is tighter than most techniques using either 3-D conformal or IMRT techniques, particularly in the absence of daily prostate localization. Zelefsky's article reveals that toxicity only begins to manifest at three months, with pronounced amplification after that time.