R. Henderson

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

PURPOSE To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. PATIENTS AND METHODS Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. RESULTS Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. CONCLUSION Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.

Protons safely allow coverage of high-risk nodes for patients with regionally advanced non-small-cell lung cancer.

Our objective was to determine if protons allow for the expansion of treatment volumes to cover high-risk nodes in patients with regionally advanced non-small-cell lung cancer. In this study, 5 consecutive patients underwent external-beam radiotherapy treatment planning. Four treatment plans were generated for each patient: 1) photons (x-rays) to treat positron emission tomography (PET)-positive gross disease only to 74 Gy (XG); 2) photons (x-rays) to treat high-risk nodes to 44 Gy and PET-positive gross disease to 74 Gy (XNG); 3) protons to treat PET-positive gross disease only to 74 cobalt gray equivalent (PG); and 4) protons to treat high-risk nodes to 44 CGE and PET-positive gross disease to 74 CGE (PNG). We defined high-risk nodes as mediastinal, hilar, and supraclavicular lymph nodal stations anatomically adjacent to the foci of PET-positive gross disease. Four-dimensional computed tomography was utilized for all patients to account for tumor motion. Standard normal-tissue constraints were utilized. Our results showed that proton plans for all patients were isoeffective with the corresponding photon (x-ray) plans in that they achieved the desired target doses while respecting normal-tissue constraints. In spite of the larger volumes covered, median volume of normal lung receiving 10 CGE or greater (V10Gy/CGE), median V20Gy/CGE, and mean lung dose were lower in the proton plans (PNG) targeting gross disease and nodes when compared with the photon (x-ray) plans (XG) treating gross disease alone. In conclusion, proton plans demonstrated the potential to safely include high-risk nodes without increasing the volume of normal lung irradiated when compared to photon (x-ray) plans, which only targeted gross disease.

PROTON RADIOTHERAPY FOR PROSTATE CANCER IS NOT ASSOCIATED WITH POST-TREATMENT TESTOSTERONE SUPPRESSION

PURPOSE Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. METHODS AND MATERIALS Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to the University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. RESULTS The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. CONCLUSIONS Conformal proton therapy to the prostate, as delivered using the University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

Proton‐based chemoradiation for synchronous bilateral non‐small‐cell lung cancers: A case report

In this case report, we present the history and treatment of a 70‐year‐old man with synchronous bilateral non‐small‐cell lung cancers with proton‐beam radiation. Surgical treatment was not feasible and optimized photon intensity‐modulated radiotherapy (IMRT) to the primary tumors would have resulted in unacceptably high normal‐tissue exposures. Proton‐beam radiation enabled radiation dose escalation and concurrent chemotherapy while maintaining normal‐tissue tolerance.

Proton Therapy for Prostate Cancer Treatment Employing Online Image Guidance and an Action Level Threshold

Purpose:The ability to determine the accuracy of the final prostate position within a determined action level threshold for image-guided proton therapy is unclear. Materials and Methods:Three thousand one hundred ten images for 20 consecutive patients treated in 1 of our 3 proton prostate protocols from February to May of 2007 were analyzed. Daily kV images and patient repositioning were performed employing an action-level threshold (ALT) of ≥2.5 mm for each beam. Isocentric orthogonal x-rays were obtained, and prostate position was defined via 3 gold markers for each patient in the 3 axes. Results:To achieve and confirm our action level threshold, an average of 2 x-rays sets (median 2; range, 0–4) was taken daily for each patient. Based on our ALT, we made no corrections in 8.7% (range, 0%–54%), 1 correction in 82% (41%–98%), and 2 to 3 corrections in 9% (0–27%). No patient needed 4 or more corrections. All patients were treated with a confirmed error of <2.5 mm for every beam delivered. After all corrections, the mean and standard deviations were: anterior-posterior (z): 0.003 ± 0.094 cm; superior-inferior (y): 0.028 ± 0.073 cm; and right-left (x) −0.013 ± 0.08 cm. Conclusion:It is feasible to limit all final prostate positions to less than 2.5 mm employing an action level image-guided radiation therapy (IGRT) process. The residual errors after corrections were very small.

When is elective pelvic lymph node irradiation indicated in definitive radiotherapy for localized prostate cancer

The objective is to define the role of elective pelvic node irradiation (EPNI) in patients treated with definitive radiotherapy for clinically localized prostate cancer. Review of the pertinent literature revealed few prospective randomized trials that evaluated the efficacy of EPNI. Although EPNI may reduce the risk of regional recurrence, its impact on biochemical progression-free survival and overall survival is unclear. Depending on the extent of the radiotherapy fields, EPNI may result in a modest increase in acute toxicity and an even smaller increase in late toxicity. EPNI may reduce the risk of regional failure in patients with high-risk prostate cancer with a likelihood of lymph node positivity of ≥15%. Although it may result in improved biochemical progression-free survival, its impact is likely modest, at best. However, EPNI should be considered for patients with a high risk of regional disease.

Image-Guided Proton Therapy for Low- and Intermediate-Risk Prostate Cancer: Three-Year Results of Two Prospective Trials

152 Background: To report outcomes in two prospective proton therapy (PT) trials for localized prostate cancer. METHODS From 2006 to 2007, 171 low- and intermediate-risk prostate cancer patients were treated with PT on prospective trials. Low-risk patients (N=89) were treated on PR01 with 78 CGE/39 fractions to the prostate. Intermediate-risk patients (N=82) were treated on PR02, a dose-escalation trial, with 78-82 CGE to the prostate and proximal seminal vesicles. Based on organ-constraint goals, 57 (69%), 13 (16%), and 12 (15%) PR02 patients received 82 CGE, 80 CGE, and 78 CGE, respectively. Toxicity was scored by CTCAE v3 and biochemical failure defined as nadir + 2 ng/mL. RESULTS The proportions of PR01 and 02 patients alive with no evidence of disease are 83 (93%) and 73 (89%); alive with disease, 1 (1%) and 1 (1%); and dead of intercurrent disease, 5 (6%) and 8 (10%), respectively. Only 2 patients had disease progression, both isolated pelvic-node recurrences. No patient died of prostate cancer or recurred locally. Grade (GR) 3 genitourinary (GU) and gastrointestinal (GI) complications occurred in 2 of 101 (2%), 0 of 13, and 4 of 57 (7%) patients receiving 78, 80, and 82 CGE, respectively. GR 3 GU toxicity occurred in 1 PR01 and 3 PR02 patients, including hematuria in 1 PR01 patient on anticoagulation; posttreatment TURP in 2 who had pretreatment (pre-tx) TURP; and dysuria in 1 with severe chronic pre-tx prostatitis. Multivariate analysis (MVA) of protocol, dose, age, prostate volume, pre-tx IPSS, pre-tx medical or surgical GU symptom management (SM), anticoagulation, and bladder wall V70 or V30 showed only pre-tx SM (P< .0001) and age (P =.007) to be associated with GR2+ toxicity. GR 3 GI toxicity occurred in 2 PR02 patients, including rectal bleeding in a patient on anticoagulation, and rectal bleeding and proctitis in a patient on anticoagulation who had a transrectal prostate biopsy. MVA of protocol, age, dose, anticoagulation, and rectal wall V70 or rectum V30 showed only rectal wall V70 (.045) and rectum V30 (.027) to be associated with GR 2+ rectal bleeding and proctitis. CONCLUSIONS PT may provide sufficiently reduced toxicity to permit further dose intensification and/or concomitant chemotherapy.