Long-Term Toxicity Following 3D Conformal Radiation Therapy for Prostate Cancer From the RTOG 9406 Phase I/II Dose Escalation Study

Presented at the Annual Meeting of the American Urological Association, Anaheim, CA, May 19–24, 2007.

Received 25 September 2008; received in revised form 6 January 2009; accepted 26 January 2009. published online 06 July 2009.

Purpose

To update the incidence of late toxicity of RTOG 9406, a three-dimensional conformal radiation therapy (3DCRT) dose escalation trial for prostate cancer.

Methods and Materials

A total of 1,084 men were registered to this Phase I/II trial of 3DCRT (eligible patients, 1,055). The dose for level I was 68.4 Gy; 73.8 Gy for level II; 79.2 Gy for level III; 74 Gy for level IV; and 78 Gy for level V. Patients in levels I to III received 1.8 Gy/fraction, and those in levels IV to V received 2.0 Gy/fraction. Disease group I patients were treated at the prostate only, group 2 patients were treated at the prostate and at the seminal vesicles with a prostate boost, and group 3 patients were treated at the prostate and seminal vesicles. The median follow-up period for surviving patients was 6.1 y (level V) to 12.1 y (level I).

Results

The incidence rates of RTOG grade 3 or less gastrointestinal or genitourinary toxicity were 3%, 4%, 6%, 7%, and 9% in group 1 and 6%, 2%, 6%, 9%, and 12% in group 2 at dose levels of I, II, III, IV, and V, respectively. In group 1, level V patients had a higher probability of grade2 late or greater gastrointestinal or genitourinary toxicity than those in levels I, II, and III (hazard ratio [HR] = 1.93, p = 0.0101; HR = 2.29, p = 0.0007; HR = 2.52, p = 0.0002, respectively). In group 2, dose level V patients had a higher probability of grade 2 or greater late gastrointestinal or genitourinary toxicity than those in dose levels II, III, and IV (HR = 2.61, p = 0.0002; HR = 2.22, p = 0.0051; HR = 1.60, p = 0.0276, respectively).

Conclusions

Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.

∗ Radiation Oncology, Washington University Medical School, St. Louis, MO

† Department of Statistics, Radiation Therapy Oncology Group, Philadelphia, PA

‡ Radiation Oncology, University of California-San Francisco, San Francisco, CA

§ Radiation Oncology, University Miami, Miami, FL

¶ Radiation Oncology, University of Michigan, Ann Arbor, MI

‖ Radiation Oncology, University of California-Davis, Davis, CA

∗∗ Radiation Oncology, University of Alberta, Edmonton, AL, Canada

†† Image-guided Therapy Center, St. Louis, MO

‡‡ Radiation Oncology, Thomas Jefferson University, Philadelphia, PA

§§ Radiation Oncology, MD Anderson Cancer Center, Houston, TX

Reprint requests to: Jeff M. Michalski, M.D., Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Campus box 8224, St. Louis, MO 63110. Tel: (314) 362-28566; Fax: (314) 747-9557

This article was supported by grants RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115, and ITC U24 CA081647 from the National Cancer Institute.

Conflict of interest: none.

PII: S0360-3016(09)00210-7

doi:10.1016/j.ijrobp.2009.01.062

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