Who enrolls onto clinical oncology trials? A radiation Patterns Of Care Study analysis.

PURPOSE: To identify factors significantly influencing accrual to clinical protocols by analyzing radiation Patterns of Care Study (PCS) surveys of 3,047 randomly selected radiotherapy (RT) patients. METHODS AND MATERIALS: Patterns of Care Study surveys from disease sites studied for the periods 1992-1994 and 1996-1999 (breast cancer, n = 1,080; prostate cancer, n = 1,149; esophageal cancer, n = 818) were analyzed. The PCS is a National Cancer Institute-funded national survey of randomly selected RT institutions in the United States. Patients with nonmetastatic disease who received RT as definitive or adjuvant therapy were randomly selected from eligible patients at each institution. To determine national estimates, individual patient records were weighted by the relative contribution of each institution and patients within each institution. Data regarding participation in clinical trials were recorded. The factors age, gender, race, type of insurance, and practice type of treating institution (academic or not) were studied by univariate and multivariate analyses. RESULTS: Overall, only 2.7% of all patients were accrued to clinical protocols. Of these, 57% were enrolled on institutional review board-approved institutional trials, and 43% on National Cancer Institute collaborative group studies. On multivariate analysis, patients treated at academic facilities (p = 0.0001) and white patients (vs. African Americans, p = 0.0002) were significantly more likely to participate in clinical oncology trials. Age, gender, type of cancer, and type of insurance were not predictive. CONCLUSIONS: Practice type and race significantly influence enrollment onto clinical oncology trials. This suggests that increased communication and education regarding protocols, particularly focusing on physicians in nonacademic settings and minority patients, will be essential to enhance accrual.

A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer.

BACKGROUND: To determine the feasibility of combining concurrent carboplatin/paclitaxel and thoracic radiotherapy (TRT) for completely resected stage II and IIIA non-small cell lung cancer. METHODS: Eligibility stipulated gross total resections with involved lymph nodes (N1 or N2), pathologic stage II or IIIA non-small cell lung cancer. TRT consisted of 50.4 Gy in 28 fractions with a boost of 10.8 Gy for extranodal extension (ENE) or 16.2 Gy for involved surgical margins. Chemotherapy was administered every 3 weeks: carboplatin (area under the curve of 5) and paclitaxel (175 mg/m2) during TRT for two cycles, with doses increased to an area under the curve of 7.5 and 225 mg/m2, respectively, for two cycles after TRT. Cox multivariate regression analysis was used to confirm independent predictors of outcome among clinical and treatment-related factors: age, T stage, N stage, presence of ENE, presence of involved surgical margins, histopathology. RESULTS: Between April 1997 and March 2001, 42 patients were enrolled. Two patients were deemed ineligible due to having T4 disease, leaving 40 patients for analysis. Ninety-two percent (37/40) of patients had T1 or T2 disease; 60% (24/40) had N2 disease. Nine patients (22.5%) had ENE and 15% (six patients) had involved surgical margins. At a median follow up of 37 months (range, 3-103; median, 68 months for living patients), the 2- and 5-year Kaplan-Meier estimates of local regional control, freedom from distant metastasis, freedom from brain metastasis, and overall survival were 92% and 88%, 77% and 59%, 87% and 71% and 72% and 44%, respectively. Fourteen patients developed distant metastasis as the initial site of failure, eight of whom had brain metastasis. Brain metastasis was the only site of failure in four of the eight patients. Multivariate regression analysis demonstrated that the only independent predictor of overall survival was histology (p = 0.02). Patients with adenocarcinoma had a 5-year overall survival of 28% versus 68% for all other cell types. There were no independent predictors of distant metastases or brain metastases on multivariate regression analysis. Treatment was tolerated reasonably well: 92% of patients (37/40) received the planned doses of TRT; 67% of patients (27/40) received all four cycles of chemotherapy. Five patients developed grade 3 esophagitis, and three patients experienced grade 3 pneumonitis. Two patients experienced grade 5 toxicity. One was treatment related due to a patient who developed grade 3 esophagitis who developed an aspiration pneumonia that progressed to acute respiratory distress syndrome. CONCLUSIONS: Our results support the Radiation Therapy Oncology Group 97-05 findings and suggest that with new and better tolerated chemotherapy regimens the strategy of concurrent TRT and chemotherapy after completely resected stage II and IIIA non-small cell lung cancer should be further explored.

Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus.

PURPOSE: A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. METHODS: A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. RESULTS: Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. CONCLUSION: Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.

The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study.

PURPOSE: A Patterns of Care Study (PCS) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. METHODS: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCS. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. RESULTS: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was >or=80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). CONCLUSIONS: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen.

International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases.

PURPOSE: To reach a consensus on a set of optimal endpoint measurements for future external beam radiotherapy trials in bone metastases. METHODS: An International Bone Metastases Consensus Working Party invited principal investigators and individuals with a recognized interest in bone metastases to participate in the two surveys and a panel meeting on their preference of choice of optimal endpoints. RESULTS: Consensus has been reached on the following: (a) eligibility criteria for future trials; (b) pain and analgesic assessments; (c) radiation techniques; (d) follow-up and timing of assessments; (e) parameters at follow-up; (f) endpoints; (g) re-irradiation; and (h) statistical analysis. CONCLUSIONS: Based on the available literature and the clinical experience of the working party members, an acceptable set of endpoints has been agreed upon for future clinical trials to promote consistency in reporting. It is intended that the consensus will be re-examined every 5 years. Areas of further research were identified.