A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT: Beyond the Abstract

Nearly 20 years ago, a new radiation therapy planning system was approved for clinical use ushering in the era of intensity modulated radiotherapy (IMRT). IMRT divides a large uniform field of radiation into many tiny beamlets, each of varying intensity or strength. This breakthrough allowed one to better conform the dose of radiotherapy to an irregular target and spare the adjacent normal tissues. Its use in prostate radiotherapy spread rapidly and today, IMRT is the most frequently used radiation modality for prostate cancer. In Arizona, at Mayo Clinic, we see a large number of men with prostate cancer.

This reflects the demographics of our state which has many older individuals who come here to retirement. As such, in 2000, we started using IMRT for prostate cancer. First, we developed a treatment planning protocol for intensity-modulated radiation therapy of the prostate using commercially available inverse planning software.[1] Then, we documented patient outcomes using this new modality and compared the results to our previous experience with 3-D radiotherapy (RT).[2] Two hundred seventy-one patients who received 3D-RT (median dose; 68.4 Gy) were compared to 145 patients who received IMRT (median dose: 75.6 Gy). The 5-year biochemical control rate (BCR) was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Image-guided IMRT allowed the delivery of higher doses of radiation with very low toxicity, resulting in improved BC.

We tried to further improve the results. This was done with IMRT by identifying an intra-prostatic lesion (IPL) (containing the highest concentration of cancer cells within the prostate) and boosting this lesion to a higher dose (simultaneous integrated boost (SIB)). Our recent report chronicles this effort. Prostate-specific membrane antigen(PSMA) is up-regulated in prostate CA.[3] Indium-111 capromab pendetide (ProstaScint™) scans employs a radiolabeled antibody specific for PSMA injected into patients and bind to malignant prostate cells that are visualized radiographically.

This prospective study assessed the feasibility and outcome of prostate IMRT delivering a ProstaScint guided simultaneous integrated boost (SIB) to an IPL. Seventy-one patients with T1N0M0 to T3N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic CT scans were co-registered for treatment planning. The entire prostate received 75.6Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82Gy as an SIB. Patients with intermediate- and high-risk disease also received 6 months and 12 months of adjuvant hormonal therapy, respectively. The study enrolled 31 low-, 30 intermediate-, and 10 high-risk patients who were followed for a median of 10 years. The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively.

The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB. The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. The described IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.

More recently, we have used the same concept using multi-parametric MRI scans to deliver a SIB. In this cohort of 78 patients, the entire prostate received 77.4Gy in 43 fractions and a SIB of 83Gy was administered to the MRI identified malignancy.[4] This resulted in a 3-year BC rate of 92% with an MRI directed SIB that was quite similar to the 3-year BC rate of 94% using ProstaScint directed SIB.[3] Thus, with careful technique integrating new imaging modalities into IMRT planning, one can improve the outcome for patients with localized prostate cancer. Thus far, we have improved the BC rates without increasing toxicity. More recently, we have begun using intensity modulated proton therapy (IMPT) which will further decrease the dose to the bladder and rectum. We have recently opened 3 new prostate cancer trials using IMPT. During the past 3 decades, we have gone from 2-D RT to 3-D RT to image guided IMRT and now, to image guided IMPT which has great promise in further improving the therapeutic index of curative prostate cancer radiotherapy.

Written by: Steven E. Schild MD, Professor and Chair, Dept of Radiation Oncology, Mayo Clinic in Arizona

References:
1. Ezzell GA, Schild SE, Wong WW. Development of a treatment planning protocol for prostate treatments using intensity modulated radiotherapy. J Appl Clin Med Phys 2001;2:59-68.

2. Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;68:1053-1058.

3. Schild MH, Schild SE, Wong WW, Vora SA, Keole SR, Vargas CE, Daniels TB, Ezzell GA, Nguyen BD, Roarke MC. A prospective trial of intensity modulated radiation therapy (imrt) incorporating a simultaneous integrated boost for prostate cancer: Long-term outcomes compared with standard image guided imrt. Int J Radiat Oncol Biol Phys 2017;97:1021-1025.

4. Schild MH, Schild SE, Wong WW, Vora SA, Silva AC, Silva AM, Daniels TB, Keole SR. Early outcome of prostate intensity modulated radiation therapy (imrt) incorporating a simultaneous intra-prostatic mri directed boost. OMICS J Radiol 2014;3.

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