First Report of NRG Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial of Samarium-153 Followed by Salvage Prostatic Fossa Irradiation in High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy.

PURPOSE: To investigate the utility of 153Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases. PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) > 1.0 ng/mL; (2) PSA > 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA > 0.2 ng/mL if N1. Patients received 153Sm (2.0 mCi/kg intravenously × 1) followed by salvage external beam radiation therapy (EBRT) to the prostatic fossa (64.8-70.2 Gy in 1.8-Gy daily fractions). No androgen deprivation therapy was allowed. The primary objective was PSA response within 12 weeks of receiving 153Sm. The secondary objectives were to: (1) assess the completion rate for the regimen of 153Sm and EBRT; (2) evaluate the hematologic toxicity and other adverse events (AEs) at 12 and 24 weeks; and (3) determine the freedom from progression rate at 2 years. RESULTS: A total of 60 enrolled eligible patients were included in this analysis. Median follow-up was 3.97 years. A PSA response was achieved in 7 of 52 evaluable patients (13.5%), compared with the 25% hypothesized. The 2-year freedom from progression rate was 25.5% (95% confidence interval 14.4%-36.7%), and the biochemical failure rate was 64.4% (95% CI 50.5%-75.2%). Samarium-153 was well tolerated, with 16 (of 60) grade 3 to 4 hematologic AEs and no grade 5 hematologic AEs. Radiation therapy was also well tolerated, with no grade 3 to 5 acute radiation therapy-related AEs and 1 grade 3 to 4 and no grade 5 late radiation therapy-related AEs. CONCLUSIONS: Trial NRG Oncology RTOG 0622 did not meet its primary endpoint of PSA response, although the regimen of 153Sm and salvage EBRT was well tolerated. Although the toxicity profile supports study of 153Sm in high-risk disease, it may not be beneficial in men receiving EBRT.

Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial.

IMPORTANCE: A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. OBJECTIVE: The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months. DESIGN, SETTING, AND PATIENTS: The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments. INTERVENTION: Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab. MAIN OUTCOMES AND MEASURES: The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI. RESULTS: Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. CONCLUSIONS AND RELEVANCE: Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00533949.

Survivorship care plans: is there buy-in from community oncology providers?

BACKGROUND: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited. METHODS: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide). RESULTS: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs. CONCLUSIONS: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.

Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates.

PURPOSE: To define clinical and dosimetric parameters correlated with the risk of clinically relevant radiation pneumonitis (RP) after thoracic radiotherapy. METHODS AND MATERIALS: Records of consecutive patients treated with definitive thoracic radiotherapy were retrospectively reviewed for the incidence of RP of Grade 2 or greater by the Common Toxicity Criteria. Dose-volume histograms using total lung volume (TL) and TL minus gross tumor volume (TL-G) were created with and without heterogeneity corrections. Mean lung dose (MLD), effective lung volume (V(eff)), and percentage of TL or TL-G receiving greater than or equal to 10, 13, 15, 20, and 30 Gy (V10-V30, respectively) were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated to estimate RP predictive values. RESULTS: Twelve cases of RP were identified in 92 eligible patients. Mean lung dose, V10, V13, V15, V20, and V(eff) were significantly correlated to RP. Combinations of MLD, V(eff), V20, and V30 lost significance using TL-G and heterogeneity corrections. Receiver operating characteristic analysis determined V10 and V13 as the best predictors of RP risk, with a decrease in predictive value above those volumes. CONCLUSIONS: Intrathoracic radiotherapy should be planned with caution when using radiotherapy techniques delivering doses of 10 to 15 Gy to large lung volumes.

Prostate position relative to pelvic bony anatomy based on intraprostatic gold markers and electronic portal imaging.

PURPOSE: To describe the relative positions and motions of the prostate, pelvic bony anatomy, and intraprostatic gold fiducial markers during daily electronic portal localization of the prostate. METHODS AND MATERIALS: Twenty prostate cancer patients were treated supine with definitive external radiotherapy according to an on-line target localization protocol using three or four intraprostatic gold fiducial markers and an electronic portal imaging device. Daily pretherapy and through-treatment electronic portal images (EPIs) were obtained for each of four treatment fields. The patients' pelvic bony anatomy, intraprostatic gold markers, and a best visual match to the target (i.e., prostate) were identified on simulation digitally reconstructed radiographs and during daily treatment setup and delivery. These data provided quantitative inter- and intrafractional analysis of prostate motion, its position relative to the bony anatomy, and the individual intraprostatic fiducial markers. Treatment planning margins, with and without on-line localization, were subsequently compared. RESULTS: A total of 22,266 data points were obtained from daily pretherapy and through-treatment EPIs. The pretherapy three-dimensional (3D) average displacement of the fiducial markers, as a surrogate for the prostate, was 5.6 mm, which improved to 2.8 mm after use of the localization protocol. The bony anatomy 3D average displacement was 4.4 mm both before and after localization to the prostate (p = 0.46). Along the superior-inferior (SI), anterior-posterior (AP), and right-left (RL) axes, the average prostate displacement improved from 2.5, 3.7, and 1.9 mm, respectively, before localization to 1.4, 1.6, and 1.1 mm after (all p < 0.001). The pretherapy to through-treatment position of the bony landmarks worsened from 1.7 to 2.5 mm (p < 0.001) in the SI axis, remained statistically unchanged at 2.8 mm (p = 0.39) in the AP axis, and improved from 2.0 to 1.2 mm in the RL axis (p < 0.001). There was no significant intrafractional displacement of prostate position or bony anatomic landmarks. An intermarker distance was identified for all fiducial markers, and 96 were followed daily. Seventy-nine percent had a standard deviation of <1 mm, and 96% were <1.5 mm. Margins were 5.1, 7.3, and 5.0 mm in the SI, AP, and RL axes, respectively, before localization and 2.7, 2.9, and 2.8 mm after localization. CONCLUSIONS: Significant interfractional motion exists for patients' prostate and pelvic bony anatomy. However, these move independently, so the pelvic bony anatomy should not be used as a surrogate for prostate motion. Fiducial markers are stable within the prostate and allow significant margin reduction when used for on-line localization of the prostate.