Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of the NRG Oncology RTOG 0517 trial.

Background: Skeletal-related events (SREs), common sequelae of metastatic cancer, are reduced by bisphosphonates. In this study, it was postulated that radiopharmaceuticals, added to bisphosphonates, could further decrease the incidence of SREs.

Methods: NRG Oncology RTOG 0517 randomized patients with breast, lung, and prostate cancer and blastic bone metastases to either zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153).

Predictive model for survival in patients having repeat radiation treatment for painful bone metastases.

Purpose: To establish a survival prediction model in the setting of a randomized trial of re-irradiation for painful bone metastases.

Methods: Data were randomly divided into training and testing sets with an approximately 3:2 ratio. Baseline factors of gender, primary cancer site, KPS, worst-pain score and age were included with backward variable selection to derive a model using the training set.

Revisiting classification of pain from bone metastases as mild, moderate, or severe based on correlation with function and quality of life.

Purpose: The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL).

Methods: We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai's Trace, Wilk's λ, and Hostelling's Trace F statistics.

Impact of reirradiation of painful osseous metastases on quality of life and function: a secondary analysis of the NCIC CTG SC.20 randomized trial.

Purpose: We previously demonstrated that 48% of patients with pain at sites of previously irradiated bone metastases benefit from reirradiation. It is unknown whether alleviating pain also improves patient perception of quality of life (QOL).

Patients And Methods: We used the database of a randomized trial comparing radiation treatment dose fractionation schedules to evaluate whether response, determined using the International Consensus Endpoint (ICE) and Brief Pain Inventory pain score (BPI-PS), is associated with patient perception of benefit, as measured using the European Organisation for Resesarch and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and functional interference scale of the BPI (BPI-FI).

Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial.

Background: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy.

Methods: We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide.

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS.

Methods And Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.

Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14.

Background: The Radiation Therapy Oncology Group (RTOG) trial 97-14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single-fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM.

Validation of a Predictive Model for Survival in Patients With Advanced Cancer: Secondary Analysis of RTOG 9714.

Background: The objective of this study was to validate a simple predictive model for survival of patients with advanced cancer.

Methods: Previous studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS).

Confirmatory factor analysis of brief pain inventory (BPI) functional interference clusters in patients with bone metastases.

To determine which of the previously proposed functional interference cluster models is most appropriate in patients with bone metastases and to determine if the cluster structures identified at baseline differed between responders and non-responders following palliative radiotherapy. METHODS: The confirmatory test data set consists of breast and prostate cancer patients treated with palliative radiotherapy between May 2003 to January 2007. Worst pain and functional interference scores were assessed using Brief Pain Inventory at baseline, 4, 8 and 12 weeks post radiation treatment.

Functional interference clusters in cancer patients with bone metastases: a secondary analysis of RTOG 9714.

Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases.

Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life.

RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer.

Purpose: The optimal dose of gemcitabine that can be used with concurrent radiation therapy for locally advanced non-small cell lung cancer has not been well defined. This trial addresses this question in an alternating sequence "ping-pong" design trial to find the maximum tolerated dose (MTD) for gemcitabine/carboplatin (Sequence A) or gemcitabine/paclitaxel (Sequence B) and thoracic radiation therapy followed by adjuvant gemcitabine/carboplatin chemotherapy.

Patients And Methods: Thirty-five patients with histologically confirmed Stage IIIA/B non-small cell lung cancer were entered into two separate sequences, each with multiple cohorts.

Can physicians accurately predict survival time in patients with metastatic cancer? Analysis of RTOG 97-14.

Purpose: To determine if physician prediction of survival duration (PSD) is accurate for patients with metastatic breast or prostate cancer.

Methods: Radiation Therapy Oncology Group 9714 (RTOG 9714) was a randomized comparison of radiotherapy schedules for treatment of bone metastases. The treating physician assigned a baseline Karnofsky Performance Score (KPS) and predicted survival duration at study entry.

Phase 2 trial of radiation plus high-dose tamoxifen for glioblastoma multiforme: RTOG protocol BR-0021.

Preclinical studies support the concept that inhibition of protein kinase C (PKC) by tamoxifen (TAM) should provide both antineoplastic effects and radiosensitization. High-dose TAM (80 mg/m2 p.o.

Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.

Background: Radiation therapy is effective in palliating pain from bone metastases. We investigated whether 8 Gy delivered in a single treatment fraction provides pain and narcotic relief that is equivalent to that of the standard treatment course of 30 Gy delivered in 10 treatment fractions over 2 weeks.

Methods: A prospective, phase III randomized study of palliative radiation therapy was conducted for patients with breast or prostate cancer who had one to three sites of painful bone metastases and moderate to severe pain.

Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.

Background: Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).

Methods: Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost.

A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04).

Purpose: The results of Phase I/II data testing beta-interferon with radiation therapy in a non-small-cell lung cancer population were promising. Based on these data, the Radiation Therapy Oncology Group (RTOG) initiated a Phase III trial to test the efficacy of beta-interferon in poor-risk patients with Stages IIIA and IIIB non-small-cell lung carcinoma.

Methods: Between September 1994 and March 1998, 123 patients were accrued to this trial.