Randal H. Henderson

Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

PURPOSE To report early outcomes with image-guided proton therapy for prostate cancer. METHODS AND MATERIALS We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. RESULTS One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. CONCLUSIONS Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer.

PURPOSE To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. METHODS AND MATERIALS A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. RESULTS Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. CONCLUSIONS Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes.

PROSPECTIVE EVALUATION OF QUALITY OF LIFE AND NEUROCOGNITIVE EFFECTS IN PATIENTS WITH MULTIPLE BRAIN METASTASES RECEIVING WHOLE-BRAIN RADIOTHERAPY WITH OR WITHOUT THALIDOMIDE ON RADIATION THERAPY ONCOLOGY GROUP (RTOG) TRIAL 0118

PURPOSE Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) +/- thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. METHODS AND MATERIALS Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. RESULTS Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. CONCLUSIONS Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population.

Proton Radiation Therapy Offers Reduced Normal Lung and Bone Marrow Exposure for Patients Receiving Dose-Escalated Radiation Therapy for Unresectable Stage III Non-Small-Cell Lung Cancer: A Dosimetric Study

INTRODUCTION The purpose of this study was to determine the potential benefit of proton radiation therapy over photon radiation therapy in patients with unresectable stage III non-small-cell lung cancer. MATERIALS AND METHODS Optimized 3-dimensional conformal photon (3DCRT), intensity-modulated radiation therapy (IMRT) and proton therapy (PT) plans were generated for 8 consecutive patients with unresectable stage III non-small-cell lung cancer using the same target goals and normal tissue constraints. The radiation exposure to non-targeted normal structures, including lung, bone marrow, esophagus, heart, and spinal cord, were compared. Photon doses are expressed in gray (Gy). Proton doses are expressed in cobalt gray equivalents (CGE). RESULTS In all patients, 3DCRT, IMRT, and PT plans, achieved the dose goals for the target volumes. Compared with the 3DCRT plans, proton plans offered a median 29% reduction in normal lung V(20) Gy (CGE), a median 33% reduction in mean lung dose (MLD), and a median 30% reduction in the volume of bone marrow receiving a dose of 10 Gy (CGE). Compared with the IMRT plans, the proton plans offered a median 26% reduction in normal lung V(20) Gy (CGE), a median 31% reduction in MLD, and a median 27% reduction in the volume of bone marrow receiving a dose of 10 Gy (CGE). CONCLUSION By reducing the volumes of normal structures irradiated, protons can potentially improve the therapeutic index for patients with unresectable stage III non-small-cell lung cancer receiving combined radiation therapy and chemotherapy.

Erectile function, incontinence, and other quality of life outcomes following proton therapy for prostate cancer in men 60 years old and younger

This study sought to evaluate patient‐reported health‐related quality of life following proton therapy for prostate cancer in men ≤60 years old.

Comparative effectiveness study of patient-reported outcomes after proton therapy or intensity-modulated radiotherapy for prostate cancer.

Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient‐reported quality‐of‐life (QOL) outcomes after proton therapy (PT) and intensity‐modulated radiation therapy (IMRT) for prostate cancer.

Elective ilioinguinal lymph node irradiation.

Abstract Most radiologists accept that modest doses of irradiation (4500–5000 rad412–5 weeks) can control subclinical regional lymph node metastases from squamous cell carcinomas of the head and neck and adenocarcinomas of the breast. There have been few reports concerning elective irradiation of the ilioinguinal region. Between October 1964 and March 1980, 91 patients whose primary cancers placed the ilioinguinal lymph nodes at risk received elective irradiation at the University of Florida. Included are patients with cancers of the vulva, penis, urethra, anus and lower anal canal, and cervix or vaginal cancers that involved the distal one-third of the vagina. In 81 patients, both inguinal areas were clinically negative; in 10 patients, one inguinal area was positive and the other negative by clinical examination. Tumor doses most commonly used were 4500–5000 rad5 weeks (180 rad to 200 rad per fraction). With a minimum two-year follow-up, there were only two regional failures in patients whose primaries were controlled; both failures occurred outside of the radiation fields. The single significant complication was a bilateral femoral neck fracture. The inguinal areas of four patients developed mild to moderate fibrosis. One patient with moderate fibrosis had bilateral mild leg edema that was questionably related to irradiation. No other instances of leg or genital edema were noted. Complications were dose-related. The advantages and disadvantages of elective ilioinguinal node irradiation versus elective inguinal lymph node dissection or no elective treatment are discussed.

Is radical prostatectomy the "gold standard" for localized prostate cancer?

The purpose of this article is to review the pertinent literature and compare the outcomes after radical prostatectomy (RP) and radiotherapy (RT). The probability of cure is similar after either RP or RT. The likelihood of significant treatment complications is probably higher after RP compared with RT. Preservation of erectile function is at least as good or better with RT compared with RP. Urinary continence is more likely to be preserved after RT compared with RP. Each treatment results in distinct patterns of adverse changes in quality of life that are worsened by factors including obesity, large prostate size, high prostate-specific antigen (PSA), and older age.

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer

PURPOSE To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. METHODS AND MATERIALS The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Data on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. RESULTS The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose-volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. CONCLUSIONS Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.

Erectile Dysfunction After Radiotherapy for Prostate Cancer

Erectile Dysfunction (ED) is a relatively common complication after radiotherapy for prostate cancer. The etiology of ED is unclear. It is likely related to age, pretreatment erectile function, androgen deprivation therapy, and the volume of tissue irradiated. It is unclear whether the dose to various parts of the penis, such as the penile bulb and corpora cavernosa, is related to the development of ED. Following radiotherapy, the early use of phosphodiesterase inhibitors probably reduces the risk of ED.