Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

PURPOSE: To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. METHODS: Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. RESULTS: Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). CONCLUSION: Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial.

PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer. METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful. RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores. CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Cardiovascular Preventive Care and Coordination of Care in Prostate Cancer Survivors: A Multi-Institutional Prospective Study.

PURPOSE: Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. They require coordinated care between cancer specialists and primary care physicians to monitor for cancer control and manage cardiovascular risk factors. METHODS AND MATERIALS: We prospectively enrolled 103 men receiving ADT with radiation therapy (RT) from 7 institutions to assess cardiovascular risk factors and survivorship care. Medical records, fasting laboratory test values, and patient-reported outcomes using a validated instrument were assessed at baseline (pretreatment) and 1 year post-RT. RESULTS: Cardiovascular disease (39%) and risk factors (diabetes, 22%; hypertension, 63%; hyperlipidemia, 31%) were prevalent at baseline. During the first year after RT completion, 63% received cardiovascular monitoring concordant with American Heart Association guidelines. Fasting laboratory test values at 1 year showed 24% with inadequately controlled blood sugar and 22% elevated cholesterol. Patient perceptions about care coordination were relatively low. At 1 year, 57% reported that their primary care physicians "always know about the care I receive at other places," 67% reported that their cancer physician "communicated with other providers I see," and 65% reported that the cancer care physician "knows the results of my visits with other doctors." CONCLUSIONS: Patients with prostate cancer who receive ADT and RT are a vulnerable population with prevalent baseline cardiovascular disease and risk factors and suboptimal survivorship care specifically related to coordinated care and cardiovascular monitoring. Clinical trials examining ways to improve the care and outcomes of these survivors are needed.

Toxicity and quality of life report of a phase II study of stereotactic body radiotherapy (SBRT) for low and intermediate risk prostate cancer.

BACKGROUND: Clinical data indicates that delivery of larger daily doses of radiation may improve the therapeutic ratio for prostate cancer compared to conventional fractionation. A phase II study of stereotactic body radiotherapy with real-time motion management and daily plan re-optimization for low to intermediate risk prostate cancer was undertaken to evaluate this hypothesis. This report details the toxicity and quality of life following treatment. METHODS: From 2009 to 2013, 60 patients with T1-T2c prostate cancer with a Gleason score of 6 and PSA ≤ 15 or Gleason score of 7 and PSA ≤ 10 were enrolled. Patients with nodal metastases, an American Urological Association symptom score > 18, or gland size > 100 g were not eligible. Patients were treated to 37 Gy in 5 fractions. Early and late genitourinary and gastrointestinal toxicity were graded based on NCI CTCAE v4.0 and quality of life was assessed by the American Urological Association symptom score, International Index of Erectile Function, and Expanded Prostate cancer Index Composite Short Form up to 36 months after treatment. RESULTS: After a median follow-up of 27.6 months, no grade 3 or greater genitourinary toxicity was observed. Four patients (6.7%) reported a late grade 2 genitourinary toxicity. One patient (1.7%) reported a late grade 3 gastrointestinal toxicity. Five patients (8.3%) developed a late grade 2 gastrointestinal toxicity. The median American Urological Association symptom score increased from 4.5 prior to treatment to 11 while on treatment (p < 0.01), but was 5 at 36 months post-treatment (p = 0.65). Median International Index of Erectile Function scores decreased from 19 to 17 over the course of follow-up (p < 0.01). Only median scores within the Expanded Prostate Cancer Index Composite Short Form sexual domain were significantly decreased at 36 months post-treatment (67.9 vs 45.2, p = 0.02). There was no significant difference in median score within the urinary, bowel, or hormonal domains at 36 months of follow-up. CONCLUSIONS: Stereotactic body radiotherapy for low to intermediate risk prostate cancer is well tolerated with limited toxicity or decrease in quality of life. Longer follow-up is necessary to assess the efficacy of treatment. TRIAL REGISTRATION: Clinicaltrials.gov NCT00941915 Registered 17 June 2009.

Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial.

PURPOSE: The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating epidermal growth factor receptor (EGFR) as a target. Erlotinib is a small-molecule inhibitor of EGFR. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. PATIENTS AND METHODS: Patients with locally advanced SCCHN were randomly assigned to receive cisplatin 100 mg/m(2) on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). The primary end point was complete response rate (CRR), evaluated by central review. The secondary end point was progression-free survival (PFS). Available tumors were tested for p16 and EGFR by fluorescent in situ hybridization. RESULTS: Between December 2006 and October 2011, 204 patients were randomly assigned. Arms were well balanced for all patient characteristics including p16, with the exception of more women on arm A. Patients on arm B had more rash, but treatment arms did not differ regarding rates of other grade 3 or 4 toxicities. Arm A had a CRR of 40% and arm B had a CRR of 52% (P = .08) when evaluated by central review. With a median follow-up time of 26 months and 54 progression events, there was no difference in PFS (hazard ratio, 0.9; P = .71). CONCLUSION: Erlotinib did not increase the toxicity of cisplatin and radiotherapy in patients with locally advanced HNSCC but failed to significantly increase CRR or PFS.

A simple model predicts freedom from biochemical recurrence after low-dose rate prostate brachytherapy alone.

OBJECTIVE: The objective of this study was to describe a simple model that predicts freedom from biochemical recurrence (FFBR) in men with prostate cancer after treatment with low-dose rate prostate brachytherapy (LDRPB) alone. MATERIALS AND METHODS: One hundred thirty-two men were treated with LDRPB alone between September 1997 and April 2001. Sixty-four percent of men had low-risk disease (prostate-specific antigen [PSA] <10, Gleason <7, and T stage or =10, Gleason > or =7, or T stage T2b). The dosimetric quantifier D90 was calculated from a computed tomography scan performed 1 month after LDRPB. The percent positive biopsies (PPB) were determined for all patients. FFBR was estimated using the product limit method. All P values are 2-sided. RESULTS: The median follow-up is 65 months. The median D90 is 138 Gy (range, 47-221 Gy). Fourteen men have developed evidence of biochemical relapse at a median of 27 months (range, 6-42 months). The 5-year FFBR rate for the entire cohort is 88%. On univariate analysis, variables found to be associated with FFBR included: PSA, Gleason score, T stage, risk group, PPB, and D90. Multivariate analysis indicated that D90, PPB, and risk group were independently associated with FFBR. Patients were categorized based on the following 3 adverse prognostic factors: D90 <140 Gy, PPB > or =50%, and intermediate-risk group. Group 1 (0 factors, n = 30), group 2 (1 factor, n = 72), and group 3 (> or =2 factors, n = 30) patients had 5-year FFBR rates of 100% (+/-0%), 92% (+/-6%), and 67% (+/-18%) (P < 0.0001). CONCLUSIONS: We have developed a simple, robust model based on implant quality and disease factors that predicts FFBR in men with prostate cancer treated with LDRPB alone.

Percentage of positive biopsies associated with freedom from biochemical recurrence after low-dose-rate prostate brachytherapy alone for clinically localized prostate cancer.

OBJECTIVES: To examine the relationship between the percentage of positive biopsies (PPBs) and freedom from biochemical recurrence (FFBR) in men treated with low-dose-rate prostate brachytherapy (LDRPB) alone. The PPBs has been associated with FFBR in men treated with radical prostatectomy and external beam radiotherapy for prostate cancer. METHODS: This report concerns 108 men treated with LDRPB alone between November 1997 and December 1999. All patients had clinically localized prostate cancer confirmed by biopsy. All men were treated with iodine-125 to 144 Gy. FFBR was estimated using the product-limit method. Putative covariates for FFBR, including T stage, Gleason score, pretreatment prostate-specific antigen level, minimal dose received by 90% of the target volume, and PPBs, were examined using the proportional hazards regression model. RESULTS: The median follow-up was 61 months. Of the 108 men, 13 developed evidence of biochemical relapse at a median of 25 months. The 5-year estimate of FFBR was 87% (95% confidence interval 81% to 93%) for the entire cohort. On univariate analysis, prostate-specific antigen, T stage, minimal dose received by 90% of the target volume, and PPBs were associated with FFBR. In the multivariate model, the PPBs was the only variable that predicted for FFBR (P = 0.002). The 5-year estimate of FFBR was 95% for patients with less than 50% PPB disease versus 63% in patients with more than 50% PPB disease (P < 0.0001). CONCLUSIONS: The PPBs is an important independent predictor of FFBR after LDRPB alone. The FFBR after LDRPB in the group of patients with more than 50% PPBs was poor.

Dosimetric quantifiers for low-dose-rate prostate brachytherapy: is V(100) superior to D(90)?

PURPOSE: The purpose of the present report is to describe the relationship between two dosimetric quantifiers (V(100) and D(90)) and freedom from biochemical recurrence (FFBR) in a cohort of men treated with low-dose-rate prostate brachytherapy (LDRPB) alone. METHODS AND MATERIALS: One hundred three men were treated with LDRPB alone between September 1997 and December 1999. All men had histologically confirmed clinically localized prostate cancer. Fifty-nine percent of the cohort had low-risk disease (defined as PSA<10, Gleason <7, and T stage /=10, Gleason>/=7, or T stage T2b). The prescription dose was 144Gy according to the Task Group 43 formalism. LDRPB was performed jointly by a radiation oncologist and a urologist. Dosimetric quantifiers (D(90), V(100)) were calculated from a CT scan performed 1 month after LDRPB. Biochemical recurrence was defined according to the ASTRO Consensus Definition. FFBR was estimated using the product-limit method. Disease-specific and treatment variables were examined as putative covariates for FFBR using the proportional hazards regression method. Univariate and multivariate methods were used. All p values are two sided. RESULTS: The median followup for the entire cohort is 61 months. The median followup of patients at risk for biochemical failure is 66 months. The median D(90) is 129Gy (range 47-221Gy), and the median V(100) is 86% (range 51-99%). Thirteen men have developed evidence of biochemical relapse at a median of 25 months (range 6-42 months). The 5-year estimate of FFBR for the entire cohort is 87% (95% CI 80-94%). On univariate analysis, disease-specific variables found to be significantly associated with FFBR included pretreatment PSA and percent positive biopsies. When considered as a continuous variable, each of the dosimetric quantifiers was associated with FFBR (V(100): p=0.007; D(90): p=0.05). D'Amico risk group classification is highly predictive of FFBR after LDRPB (HR 5.68, p=0.003). Multivariate analysis indicated that each dosimetric quantifier was independently associated with FFBR, but due to the high degree of correlation (Pearson correlation coefficient 0.94, p<0.0001) between the dosimetric quantifiers both could not be included simultaneously in the model. In the two models explored, V(100) was at least as good as D(90) in predicting FFBR. CONCLUSIONS: Dosimetric quantifiers (V(100) and D(90)) are independent predictors of FFBR after treatment with LDRPB alone. In our experience, V(100) seems to be at least equivalent (and perhaps superior) to D(90) for predicting FFBR.

Lessons learned from randomised clinical trials in adult low grade glioma.

"Lesson" is a Middle English word that has been defined as "a passage from sacred writings read in a service of worship" as well as "something learned by study or experience". The term is quite appropriate in assessment of what has been learned from randomised trials in adult low-grade gliomas, since the treatment of these tumours has traditionally been guided as much by belief as by fact. Therefore, when assessing these trials we can apply the principles of hermeneutics. Thus, the first meaning of "lesson" given here can be described as literal, whereas the second may be seen as figurative. Since hermeneutics may also refer to an in-depth analysis of a particular text, the investigators will present their interpretation of data from randomised trials. The goal is to show that the lessons learned are not necessarily literal or dogmatic but can be much more allegorical in nature.

Publication rate of abstracts from the annual ASTRO meeting: comparison with other organizations.

PURPOSE: One of the explicit goals of the American Society of Therapeutic Radiology and Oncology (ASTRO) is to promote research and disseminate research results. In the past few years, ASTRO has required that manuscripts be submitted for publication for all papers accepted for oral presentation at its annual meeting. The purpose of this study was to determine the publication rate of abstracts accepted for oral presentation at ASTRO's 1999, 2000, and 2001 annual meetings. MATERIALS AND METHODS: The authors reviewed the proceedings of ASTRO's annual meetings in 1999, 2000, and 2001 to identify all abstracts accepted for oral presentation. The following information was collected: year of presentation, study design (phase I or II, phase III, or retrospective), country of origin (domestic or foreign), abstract category (clinical or nonclinical), disease site (if applicable), publication (yes or no), publication date, and publishing journal. A computer-based search using Medline was used to determine whether the full publication of each abstract had occurred. The computer search included publication up to November 1, 2003. RESULTS: The publication rate was 56% (452 of 802). There was no difference in publication rate according to country of origin (domestic 56%, foreign 57%; p = NS), abstract category (clinical 59%, nonclinical 48%; p = NS), or study design. Half of the published abstracts were published within 1 year of the meeting, and 90% were published within 2 years. The 452 publications were distributed among 54 different journals. The majority of papers were published in the International Journal of Radiation Oncology, Biology and Physics (62%), followed by the Journal of Clinical Oncology (8%) and Radiotherapy and Oncology (3%). CONCLUSIONS: Slightly more than one-half of the abstracts accepted for oral presentation at the annual ASTRO meeting are published within 2 years. This rate is similar to those of other specialties and suggests that ASTRO is succeeding in its mission to promote and disseminate research.