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William F Regine

Publications and source records attributed to William F Regine.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of surgery plus radiotherapy versus radiotherapy alone for metastatic epidural spinal cord compression.

PURPOSE: A recent randomized clinical trial has demonstrated that direct decompressive surgery plus radiotherapy was superior to radiotherapy alone for the treatment of metastatic epidural spinal cord compression. The current study compared the cost-effectiveness of the two approaches. METHODS AND MATERIALS: In the original clinical trial, clinical effectiveness was measured by ambulation and survival time until death. In this study, an incremental cost-effectiveness analysis was performed from a societal perspective. Costs related to treatment and posttreatment care were estimated and extended to the lifetime of the cohort. Weibull regression was applied to extrapolate outcomes in the presence of censored clinical effectiveness data. RESULTS: From a societal perspective, the baseline incremental cost-effectiveness ratio (ICER) was found to be $60 per additional day of ambulation (all costs in 2003 Canadian dollars). Using probabilistic sensitivity analysis, 50% of all generated ICERs were lower than $57, and 95% were lower than $242 per additional day of ambulation. This analysis had a 95% CI of -$72.74 to 309.44, meaning that this intervention ranged from a financial savings of $72.74 to a cost of $309.44 per additional day of ambulation. Using survival as the measure of effectiveness resulted in an ICER of $30,940 per life-year gained. CONCLUSIONS: We found strong evidence that treatment of metastatic epidural spinal cord compression with surgery in addition to radiotherapy is cost-effective both in terms of cost per additional day of ambulation, and cost per life-year gained.

Canada↗
PubMed2006

Adjuvant therapy for pancreatic cancer: current status, future directions.

Progress in the management of adenocarcinoma of the pancreas has clearly been documented in recent years. Surgical outcomes have improved dramatically, and the preponderance of data from randomized clinical trials affirm that adjuvant therapy, in the form of combination chemoradiotherapy, improves outcomes over surgery alone in patients with resected disease. Newer chemotherapeutic agents such as gemcitabine have led to significant improvements over 5-fluorouracil alone, and patients have benefited from improved methods of delivering conformal radiotherapy. As the clinical benefits of postoperative adjuvant therapy become increasingly evident, researchers have begun to explore the utility of including preoperative or "neoadjuvant" regimens to standard 5-fluorouracil-based chemoradiotherapy. Initial results with this strategy are promising, and will likely influence the direction of future research. A growing understanding of the molecular biology of the disease has opened doors to rich new areas of research, and targeted therapies will likely play an important role in newly developing treatment paradigms. Just cause for optimism exists, but much work remains to be done. New adjuvant therapies need to be developed and tested, in carefully designed, well-executed, efficient clinical trials.

Chemotherapy, Adjuvant↗
PubMed2006

Feasibility of delivering grid therapy using a multileaf collimator.

The feasibility of using a multileaf collimator (MLC) for grid therapy is demonstrated in this study. Grids with the projected field openings of 10 mm x 10 mm and 5 mm x 5 mm were created using multiple MLC-shaped fields. The deposited doses were measured with films at different depths in a solid water phantom and compared to those of Cerrobend grid collimators of similar hole sizes and hole separations. At the depth of maximum dose (dmax), the valley-to-peak dose ratios of the MLC grids were found to be about 11% and 19% for the respective 10 mm x 10 mm and 5 mm X 5 mm grid openings, and those of the corresponding grid blocks were about 15% and 20%. To quantify the dose contributed by transmission in the blocked areas due to the limited leaf thickness, Monte Carlo simulations (based on convolution/superposition method) were performed to calculate the doses in the solid water phantom using an ideal MLC with no leakage and perfect divergence in both the leaf end and side. About 7% reduction in the valley-to-peak dose ratio was found for both grid sizes at dmax. The results clearly showed that MLCs can be used to provide grid treatments with at least as good dosimetric properties as those of the Cerrobend grid blocks, though the former would in general require a longer delivery time.

Dose Fractionation, Radiation↗
PubMed2006

Spatially fractionated GRID radiation treatment of advanced neck disease associated with head and neck cancer.

Advanced nodal disease associated with head and neck cancer warrants aggressive, often multi-modality therapy to maximize local-regional control. The expansion of a novel treatment paradigm developed by our institution includes the addition of a single-fraction of high dose spatially-fractionated radiation (GRID) to a conventional course of treatment. Between 1995 and 2002 a series of 27 patients (median age 65) with bulky N2-3 disease were treated. Median nodal tumor size was 7 cm. Two groups of patients were evaluated. Group 1 (N=14) patients received a median neck dose 69 Gy (range 54-79 Gy) plus GRID treatment. Group 2 (N=13) patients received a median neck dose of 59 Gy (range 54-72 Gy) plus GRID treatment followed by planned neck dissection. Patients were evaluated for local-regional control, pathological response, survival, and morbidity. Median time to follow-up for Group 1 was 10 months (range 3-44 months). Neck control was 93%. Disease specific survival was 50%. Morbidity was limited to soft-tissue related damage and was mild. Median time to follow-up for Group 2 was 38 months (range 5-116 months). Pathologic complete response rate was 85%. Overall neck control rate was 92%. Disease specific survival was 85%. Surgical morbidity was limited to three wound healing complications. GRID treatment may be safely added to conventional treatment management of locally advanced neck disease related to cancer with acceptable morbidity. It may improve pathologic complete response rates in those patients who undergo planned neck dissection, possibly leading to improved survival. In patients with inoperable bulky disease, addition of GRID enhances local-regional control.

Adult↗
PubMed2005

Long-term results of hyperfractionated radiation and high-dose intraarterial cisplatin for unresectable oropharyngeal carcinoma.

BACKGROUND: In this report, the authors present the results from a study of patients with unresectable oropharyngeal squamous cell carcinomas who were treated on a protocol of hyperfractionated radiation and high-dose intraarterial cisplatin (HYPERRADPLAT) at the University of Kentucky. METHODS: The study was designed as a prospective, single-armed case series that was conducted in the setting of a single, academic, tertiary referral center. The patient cohort consisted of 24 previously untreated patients who were diagnosed with unresectable oropharyngeal carcinoma and were treated on the HYPERRADPLAT regimen, which included hyperfractionated external beam radiotherapy (1.2 grays [Gy] twice daily) was given for 5 weeks (60 Gy) followed by high-dose intraarterial cisplatin (150 mg/m2) and sodium thiosulfate. Shrinking "large-field" portals were started on Week 6 and finished on Week 7 with a cumulative dose of 76.8-81.6 Gy. The main outcome measures of the study were the primary and neck response rates, the 2-year and 5-year overall survival and disease-specific survival rates, and acute and late treatment morbidity. RESULTS: The median follow-up was 77 months. Complete response rates at the primary and regional lymph nodes were both 88%. The 2-year overall survival and disease-specific survival rates were 57% and 68%, respectively; whereas the 5-year overall survival and disease-specific survival rates were 33% and 42%, respectively. Two patients had Grade 4 mucosal toxicity, and no patient experienced neurologic or significant hematologic toxicities. Within 1 year of treatment, 58% of patients had used a feeding tube. CONCLUSIONS: The HYPERRADPLAT regimen produced excellent response rates and overall survival rates comparable to those achieved by patients who had unresectable oropharyngeal carcinomas. Tolerance of the therapy was good, and further studies using HYPERRADPLAT with induction therapy may improve outcomes further in this subset of patients with unfavorable disease.

Adult↗
PubMed2005

Cancer caregiving and subjective stress: a multi-site, multi-dimensional analysis.

Although research has emerged documenting the psychosocial impact of family care for cancer patients, few efforts capture the multi-dimensional nature of cancer caregiving stress, particularly among socioeconomically diverse samples. Utilizing data collected from cancer caregivers at a non-urban, Southern US site and an inner-city, Northeastern US site (N=233), the present study identified predictors of multiple dimensions of caregivers' subjective stress (i.e. emotional appraisals of care demands). Various indicators representing the sociodemographic context of care, cancer care demands, and psychosocial resources were found to exacerbate or buffer caregivers from feelings of exhaustion, role entrapment, and loss of intimacy with the cancer patient. The multivariate regression model also emphasized the diffuse yet potent role care recipient mood problems and caregiver mastery/optimism have on multiple dimensions of subjective stress. The findings offer a number of recommendations for future research and practice focused on informal cancer care.

Adaptation, Psychological↗
PubMed2005

Concomitant GRID boost for Gamma Knife radiosurgery.

We developed an integrated GRID boost technique for Gamma Knife radiosurgery. The technique generates an array of high dose spots within the target volume via a grid of 4-mm shots. These high dose areas were placed over a conventional Gamma Knife plan where a peripheral dose covers the full target volume. The beam weights of the 4-mm shots were optimized iteratively to maximize the integral dose inside the target volume. To investigate the target volume coverage and the dose to the adjacent normal brain tissue for the technique, we compared the GRID boosted treatment plans with conventional Gamma Knife treatment plans using physical and biological indices such as dose-volume histogram (DVH), DVH-derived indices, equivalent uniform dose (EUD), tumor control probabilities (TCP), and normal tissue complication probabilities (NTCP). We found significant increase in the target volume indices such as mean dose (5%-34%; average 14%), TCP (4%-45%; average 21%), and EUD (2%-22%; average 11%) for the GRID boost technique. No significant change in the peripheral dose coverage for the target volume was found per RTOG protocol. In addition, the EUD and the NTCP for the normal brain adjacent to the target (i.e., the near region) were decreased for the GRID boost technique. In conclusion, we demonstrated a new technique for Gamma Knife radiosurgery that can escalate the dose to the target while sparing the adjacent normal brain tissue.

Algorithms↗
PubMed2004

Factors predicting local tumor control after gamma knife stereotactic radiosurgery for benign intracranial meningiomas.

PURPOSE: To determine the long-term outcomes and prognostic factors in benign intracranial meningiomas treated with gamma knife stereotactic radiosurgery (GK-SRS). METHODS AND MATERIALS: Between 1992 and 2000, 162 patients with benign meningiomas were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up was available in 137 patients. All patients underwent magnetic resonance imaging (MRI)-based treatment planning. Serial MRIs and clinical exams were performed to assess tumor response. GK-SRS was the primary treatment in 85 patients (62%), whereas 52 patients (48%) had prior surgical resections. The median prescribed dose was 14 Gy (range, 4-25 Gy) to the 50% isodose line. The median tumor volume, treatment volume, and conformity index were 4.5 cc (range, 0.32-80.0 cc), 6.3 cc (range, 1.0-75.2 cc), and 1.34 (range, 0.65-3.16), respectively. The median follow-up for the entire cohort was 4.5 years (range, 0.33-10.5 years). The following factors were included in the statistical analysis for disease-free survival (DFS) and overall survival (OS): sex, age, dose, gross tumor volume (GTV), conformity index (CI), and dural tail coverage. RESULTS: Serial MRI analysis was available in 121 patients (88.3%). Decrease in tumor size was observed in 34 patients (28.1%), whereas there was no change in 77 patients (63.6%), for a crude radiographic control rate of 91.7%. Increase in tumor size was seen in 10 patients (8.3%). New neurologic deficits attributed to the treatment developed in 10 patients (8.3%). The mean DFS and OS for the entire cohort are 4.6 years and 5.0 years, respectively. The 5-year actuarial DFS and OS were 86.2% and 91.0%, respectively. Univariate analysis revealed GTV, sex, CI, and dural tail treatment to be significant prognostic factors. Patients with GTV < or =10 cc also had longer survivals, with the 5-years DFS and OS of 91.9% vs. 68.0% (p = 0.038) and 100% vs. 59.7% (p = 0.0001), respectively. The 5-years actuarial DFS and OS for females vs. males were 90.2% vs. 74.2% (p = 0.0094) and 91.6% vs. 89.1% (p = 0.016), respectively. Patients with CI > or =1.4 achieved a longer DFS, with a 5-year DFS of 95.2% vs. 77.3% (p = 0.01). Patients who had the dural tail treated also had higher 5-year DFS (96.0% vs. 77.9%, p = 0.038). Patients with lower conformity (i.e., CI > or =1.4) tended to have the dural tail covered in the prescription isodose line (p = 0.04). The only factor significant in the multivariate analysis was for patients with GTV >10 cc, who had a worse DFS (hazard ratio 4.58, p = 0.05). CONCLUSIONS: This report adds to the literature that supports the efficacy and safety of GK-SRS in the management of patients with benign intracranial meningiomas. Our report identified male patients, patients with a CI <1.4, and tumor size greater than 10 cc to have a worse prognosis. Patients who were treated with less conformal plans to cover the dural tail had better outcomes. Our data clearly demonstrate the need to adequately cover the dural tail in patients treated with GK-SRS for benign intracranial meningiomas.

Adolescent↗
PubMed2004

Gamma knife surgery for trigeminal neuralgia: outcome, imaging, and brainstem correlates.

PURPOSE: To review our results with gamma knife surgery (GKS) in the treatment of trigeminal neuralgia (TN), and to determine whether pain relief, medication usage, and the development of facial numbness are affected by trigeminal nerve compression, MRI imaging quality, or brainstem radiation dose. METHODS AND MATERIALS: One hundred twelve patients with TN refractory to medical or surgical management were treated at the University of Maryland Gamma Knife Center between June 1996 and July 2001. Patients were treated using a 4-mm shot to the trigeminal nerve, at a point 2-4 mm anterior to the root entry zone of the nerve into the pons. The median dose prescribed was 75 Gy (range, 60-80 Gy). T1- and T2-weighted, axial, 1.5-mm-thick MRI images were obtained using three-dimensional gradient echo acquisition after contrast injection for treatment planning. MRI images were evaluated for imaging quality (i.e., the adequacy of visualization of the affected prepontine trigeminal nerve), the presence of trigeminal nerve compression, and the brainstem dose. Follow-up data were obtained via telephone interviews, and patients were asked to rate their pre-GKS and post-GKS pain using the Barrow Neurological Institute (BNI) Pain Intensity Scale. Patients were also asked about side effects from GKS and were asked to rate any facial numbness on the BNI Facial Numbness Scale. Medication use, time to pain response, and duration of relief were also evaluated. RESULTS: Ninety-six patients who had follow-up data were included in the analysis. Eighty-six patients (89.6%) responded to GKS with an improvement in BNI pain class. Ten patients (10.4%) were found to have an MRI of poor quality, 30 (31.3%) fair quality, and 56 (58.3%) good quality. Forty-two (43.8%) received 10% of the maximal dose to the brainstem edge, whereas 54 (56.2%) received 20%. Eleven (11.5%) patients were found to have obvious nerve compression by MRI. Imaging quality (p = 0.1863), presence of compression (p = 0.1147), and brainstem dose (p = 0.3168) did not correlate with treatment response. There was also no correlation between these variables (MRI quality, compression, and brainstem dose) and medication use (p = 0.5372, p = 0.0913, p = 0.6832, respectively). Facial numbness was the only side effect experienced. Thirteen patients reported varying degrees of facial numbness, but there was no correlation between imaging quality (p = 0.0600), brainstem dose (p = 0.6773), and presence of compression (p = 0.5785) with the development of facial numbness. CONCLUSIONS: Gamma knife surgery is effective in the treatment of TN and has a favorable side effect profile. Treatment response and the development of facial numbness do not correlate with MRI imaging quality, presence of nerve compression, or radiation dose to the brainstem.

Adult↗
PubMed2004

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.

Adult↗
PubMed2004

Stereotatic radiosurgery of 468 brain metastases < or =2 cm: implications for SRS dose and whole brain radiation therapy.

PURPOSE: The national standard stereostatic radiosurgery (SRS) dose for brain metastases < or =2 cm is 24 Gy as established by the Radiation Therapy Oncology Group study 90-05, in which planned whole brain radiotherapy (WBRT) was not used. On the basis of our institutional experience, the goal of this study was to determine the optimal SRS dose and influence of WBRT on local tumor control among 468 < or =2-cm metastases. METHODS AND MATERIALS: Between October 1992 and May 2001, 468 newly diagnosed or recurrent < or =2-cm brain metastases, among 160 patients, were treated with SRS (dose range, 7-30 Gy; median, 20). A total of 240 metastases received planned WBRT (range, 6.75-50.4 Gy; median, 40.5) vs. 228 metastases that did not. The variables tested by multivariate analysis for their potential effect on tumor control included histologic type, site of metastasis, primary diagnosis, tumor volume, SRS dose, newly diagnosed vs. recurrent metastasis, and planned WBRT vs. no planned WBRT. RESULTS: Follow-up ranged from 1 to 82 months (median 7). On multivariate analysis, the addition of WBRT was the most significant predictor of local tumor control. Overall, patients who received WBRT had superior local tumor control rates (97% vs. 87% in those who did not receive WBRT; p = 0.0001). Patients receiving WBRT and SRS > or =20 Gy achieved local control rates of 99% compared with 91% control rates when treated with WBRT and SRS <20 Gy (p = 0.0029). Increasing the SRS dose to >20 Gy resulted in no improvement in local tumor control and a higher rate of Grade 3 and 4 neurotoxicity, approaching statistical significance (5.9% vs. 1.9%, p = 0.078). CONCLUSION: First, optimal control of brain metastasis < or =2 cm was seen with 20-Gy SRS combined with planned WBRT. Second, SRS doses >20 Gy resulted in no obvious improvement in local control and appeared to be associated with a greater rate of complications.

Adolescent↗
PubMed2004

Low-dose fractionated radiation as a chemopotentiator of neoadjuvant paclitaxel and carboplatin for locally advanced squamous cell carcinoma of the head and neck: results of a new treatment paradigm.

PURPOSE: Current therapies for locally advanced squamous cell carcinoma of the head and neck (SCCHN) result in 50% long-term remission. Low-dose radiotherapy (<100 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon but has not been used in the clinical setting. On the basis of the demonstrated synergy between chemotherapy and low-dose fractionated RT, a novel neoadjuvant therapy was designed using low-dose fractionated RT as a chemopotentiator for locally advanced SCCHN. METHODS AND MATERIALS: Forty patients with locally advanced SCCHN received paclitaxel (225 mg/m2), carboplatin (area under the curve of 6), and four 80-cGy fractions of radiotherapy (two each on Days 1 and 2). This sequence was repeated on Days 22 and 23. RESULTS: Of the 40 patients enrolled, 39 were assessable. Grade 3 or worse toxicities included neutropenia (50%), infection (13%), arthralgias/myalgias (3%), skin (8%), lung (3%), and allergic reaction (3%), with no Grade 5 toxicity. The response was assessed radiographically and by panendoscopy. At the primary site, 11 patients (28%) had a complete response, 24 (62%) had a partial response, and 4 (10%) had stable disease. Of those with lymph node involvement, 10 (31%) had a complete response, 12 (38%) a partial response, 9 (28%) had stable disease, and 1 (3%) had progressive disease. The overall response rate was 82%. CONCLUSION: Low-dose fractionated RT combined with paclitaxel and carboplatin is effective in SCCHN and has a similar toxicity profile to chemotherapy alone. This novel approach provided a response rate of 90% at the primary site and a nodal response rate of 69%. Additional scientific investigation of this new treatment paradigm is warranted.

Adult↗
PubMed2004

Feasibility of neurocognitive outcome evaluations in patients with brain metastases in a multi-institutional cooperative group setting: results of Radiation Therapy Oncology Group trial BR-0018.

PURPOSE: A multi-institutional trial was conducted by the Radiation Therapy Oncology Group (RTOG) to test the feasibility of performing a test battery consisting of five neurocognitive measures and a quality-of-life instrument in patients with brain metastases. METHODS AND MATERIALS: The major eligibility requirements included histologic proof of a primary malignancy, measurable single or multiple brain metastases, Zubrod performance status of 0-1, neurologic function status of 0-2, and "certification" for administration of neurocognitive assessments. This certification process required either attendance at an RTOG neurocognitive assessment training workshop or review of an instructional video, followed by submission of an audiotape of mock/simulated test sessions for central review. The test battery included the following measures: the Mini-Mental Status Examination, Hopkins Verbal Learning Test, Verbal Fluency/Controlled Word Association Test, Ruff 2 and 7 test, Trailmaking Test, and Profile of Mood States-Short Form. The primary objective of this trial was to establish whether patients were able to complete this test battery. Compliance was defined as successful completion of a test measure. The test battery was to be administered just before, at completion of, and 1 month after whole brain radiotherapy to 37.5 Gy at 2.5 Gy/fraction once daily. Fifty-nine patients were enrolled in the trial. RESULTS: The patient characteristics included 32% > or =65 years; 44% with Zubrod performance status of 0; and 81% with multiple brain metastases. The overall compliance rate for administration and completion of the five neurocognitive measures and a quality-of-life instrument before treatment, at treatment completion, and 1 month after treatment was > or =95%, > or =84%, and > or =70%. The most common causes of noncompliance were patient-related factors (e.g., performance status or inability to understand test instructions) and not institutional error. CONCLUSION: Neurocognitive evaluation of patients with brain metastases in a multi-institutional and cooperative group setting is feasible using the test battery and certification process used in this study. This battery and certification process will be incorporated into future RTOG brain tumor trials.

Affect↗
PubMed2004

The evolving role of postoperative adjuvant radiation therapy for pancreatic cancer.

The benefit of postoperative adjuvant chemoradiation in the treatment of resected pancreatic cancers was first established by a randomized trial conducted by the Gastrointestinal Tumor Study Group in 1974. During the past 3 decades, treatment has evolved toward more dose-intensive regimens of chemoradiation. Historical split-course conventional radiation therapy has been replaced by continuous-course radiotherapy to higher doses, and gemcitabine is being actively investigated as a potentially more effective agent than 5-fluorouracil. This article critically examines the results of important randomized multi-institutional trials and reviews the evolution toward dose-intensive adjuvant treatment regimens. Implications of the recently completed intergroup study are discussed, modern radiation therapy delivery techniques are reviewed, and suggestions for future trials are made.

Adenocarcinoma↗