S. Lei

A Pilot Study of Intensity Modulated Radiation Therapy with Hypofractionated Stereotactic Body Radiation Therapy (SBRT) Boost in the Treatment of Intermediate- to High-Risk Prostate Cancer

Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

BackgroundThe CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.MethodsTwenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.ResultsAll 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.ConclusionsHypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

Histopathologic effects of hypofractionated robotic radiation therapy on malignant and benign prostate tissue.

We describe the first histopathologic analysis of prostatic tissue following hypofractionated robotic radiation therapy. A 66 year-old man presented with stage II, low risk adenocarcinoma of the prostate and underwent elective conformal hypofractionated radiation therapy. His pretreatment evaluation revealed T1c adenocarcinoma, Gleasons grade 3 + 3 = 6 and a prostate specific antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy) was completed on an Internal Review Board approved protocol. One year later, he developed progressive urinary retention. Transurethral prostatic resection was performed to alleviate obstructive symptoms. Bilobar hypertrophy was observed without evidence of stricture. Histolopathologic analyses of resected prostate tissues revealed changes consistent with radiation treatment, including cellular changes, inflammation, glandular atrophy and hyperplasia. There was no evidence of residual cancer, fibrosis or necrosis. The patients postoperative course was uneventful with post-treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.

Stereotactic body radiation therapy (SBRT) following procedures for benign prostatic hyperplasia (BPH): A report on early toxicity.

165 Background: When treating patients with prostate cancer, hypofractionation with SBRT takes advantage of radiobiologically favorable factors as compared to conventional fractionation. However, this may increase the risk of urinary toxicity, especially in patients with prior procedures for BPH. Herein, we report early urinary toxicity following SBRT in patients with a history of procedures for BPH. METHODS Thirty three patients treated with SBRT for localized prostate cancer from February 2009 to October 2011 at Georgetown University Hospital with history of a prior procedure for BPH were included in this retrospective analysis. Treatment was delivered using the CyberKnife with doses of 35 Gy-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.3. Cystoscopy findings were retrospectively reviewed. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA). RESULTS The median age was 70 years (range, 64 - 84). The median follow-up time was 18.7 months (range 9.2 - 38.9). Grade 2 or 3 urinary toxicity occurred in 9 patients and there were no grade 4 or 5 toxicities. Hematuria occurred in 12 patients. The median time to onset of hematuria from SBRT was 6 months (range 1 - 30). Grade 1 hematuria occurred in 7 patients, grade 2 in 4 patients and 1 patient experienced grade 3. Cystoscopy was performed in 9 of these patients at a median time of 9 months (range 3-27). Eight had hyperemia or evidence of bleeding from the prostatic urethra and 5 of these patients also had evidence of bleeding from the bladder neck/wall. All patients except one, who died from other causes, are still being followed and hematuria has resolved in 9 of the 12 patients. The median baseline AUA symptom score of 7 increased to 11 at 1 month, however decreased to a median score of 6 at 3 months. The median AUA symptom score increased to 9 at 1 year. CONCLUSIONS A history of prior transurethral resection of prostate may predispose patients to increased urinary toxicity and hematuria following prostate SBRT. Stricter urethra/bladder neck dosimetric criteria or alternative fractionation regimens may be required to decrease urinary toxicity in these patients.