William F. Regine

Bio: William F. Regine is an academic researcher from University of Maryland, Baltimore. The author has contributed to research in topics: Radiation therapy & Pancreatic cancer. The author has an hindex of 51, co-authored 282 publications receiving 12693 citations. Previous affiliations of William F. Regine include University of Maryland Medical System & University of Maryland Marlene and Stewart Greenebaum Cancer Center.

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.

Abstract: Context.—For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established.Objective.—To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival.Design.—Multicenter, randomized, parallel group trial.Setting.—University-affiliated cancer treatment facilities.Patients.—Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study.Interventions.—Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively.Main Outcome Measures.—The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently.Results.—Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P <.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P =.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent.Conclusions.—Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.

Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial.

Abstract: Context Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m 2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m 2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m 2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P 85%). Conclusions The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00003216

A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases.

Abstract: Purpose: Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). Methods and Materials: A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. Results: Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT ( p = 0.33, hazard ratio=1.09). Conclusions: Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.

Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

Abstract: ContextThe role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.ObjectiveTo test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.Design, Setting, and PatientsOpen, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups.InterventionPatients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175).Main Outcome MeasuresPrimary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat).ResultsMore than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank).ConclusionsPostoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas.Trial Registrationisrctn.org Identifier: ISRCTN34802808

Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.

Abstract: Summary Background It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. Methods Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test–Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. Findings After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0·0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. Interpretation Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases. Funding No external funding was received.