Showing papers by "Walter J. Curran published in 2009"
TL;DR: A PTV(boost) margin of 1cm or less did not appear to increase the risk of marginal and/or distant tumor failures compared with other published series, suggesting that treatment margins for glioblastoma can be reduced.
Abstract: Purpose To evaluate the pattern of failure after limited margin radiotherapy for glioblastoma. Methods and Materials We analyzed 62 consecutive patients with newly diagnosed glioblastoma treated between 2006 and 2008 with standard fractionation to a total dose of 60Gy with concurrent temozolomide (97%) or arsenic trioxide (3%). The initial clinical target volume included postoperative T2 abnormality with a median margin of 0.7cm. The boost clinical target volume included residual T1-enhancing tumor and resection cavity with a median margin of 0.5cm. Planning target volumes added a 0.3- or 0.5-cm margin to clinical target volumes. The total boost planning target volume (PTV boost ) margin was 1cm or less in 92% of patients. The volume of recurrent tumor (new T1 enhancement) was categorized by the percent within the 60-Gy isodose line as central (>95%), infield (81–95%), marginal (20–80%), or distant ( boost with a 2.5-cm margin were created for each patient. Results With a median follow-up of 12 months, radiographic tumor progression developed in 43 of 62 patients. Imaging was available for analysis in 41: 38 (93%) had central or infield failure, 2 (5%) had marginal failure, and 1 (2%) had distant failure relative to the 60-Gy isodose line. The treated PTV boost (median, 140cm 3 ) was, on average, 70% less than the PTV boost with a 2.5-cm margin (median, 477cm 3 ) ( p Conclusions A PTV boost margin of 1cm or less did not appear to increase the risk of marginal and/or distant tumor failures compared with other published series. With careful radiation planning and delivery, it appears that treatment margins for glioblastoma can be reduced.
156 citations
TL;DR: The addition of bevacizumab to chemoradiotherapy followed by bevacsumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer.
Abstract: Purpose The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR). Patients and Methods Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA). Results Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95%...
128 citations
TL;DR: There is no evident reduction in survival by delaying initiation of RT within the relatively narrow constraint of 6 weeks, and an unanticipated yet significantly superior outcome was identified for patients for whom RT was delayed beyond 4 weeks from surgery.
Abstract: Purpose To analyze the Radiation Therapy Oncology Group (RTOG) database of patients with glioblastoma and appraise whether outcome was influenced by time to initiation of radiation therapy (RT). Patients and Methods From 1974 through 2003, adult patients with histologically confirmed supratentorial glioblastoma were enrolled onto 16 RTOG studies. Of 3,052 enrolled patients, 197 patients (6%) were either initially rendered ineligible or had insufficient chronologic data, leaving a cohort of 2,855 patients for the present analysis. We selected four patient groups based on the interval from surgery to the start of RT: 2 weeks, 2 to 3 weeks, 3 to 4 weeks, more than 4 weeks to the protocol eligibility limit of 6 weeks. Survival times were estimated by the Kaplan-Meier method. Multivariate analysis incorporated variables of time interval, recursive partitioning analysis (RPA) class, and treatment regimen.
104 citations
University of Michigan1, Radiation Therapy Oncology Group2, Washington University in St. Louis3, University of Texas MD Anderson Cancer Center4, University of California, Davis5, St. Joseph's Hospital and Medical Center6, Thomas Jefferson University7, University of Texas Health Science Center at San Antonio8, University of Wisconsin-Madison9
TL;DR: The study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.
Abstract: Purpose To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM). Methods and Materials A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV 1 ), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV 2 , defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV 2 3 ; Group 2: PTV 2 ≥75 cm 3 ). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m 2 was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced. Results Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade ≥3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1–12.5 months). Median survival in Group 1 was 11.6–19.3 months. Median survival in Group 2 was 8.2–13.9 months. Conclusions Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.
94 citations
TL;DR: Bortezomib administered at its typical "systemic" dose is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies.
Abstract: Purpose To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m 2 /dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m 2 starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non–dose-limiting toxicity, and treatment response. Results A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m 2 /dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion Bortezomib administered at its typical "systemic" dose (1.3 mg/m 2 ) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.
88 citations
TL;DR: A lower total dose at 46.8 Gy was associated with a 100% local control tumor rate and a greater hearing preservation rate and an additional dose reduction is justified to achieve the optimal dose that will yield the greatest hearing preservation rates without compromising tumor control for these patients.
Abstract: Purpose To describe our initial experience of fractionated stereotactic radiotherapy dose reduction comparing two dose cohorts with examination of tumor control rates and serviceable hearing preservation rates. Methods and Materials After institutional review board approval, we initiated a retrospective chart review to study the hearing outcomes and tumor control rates. All data were entered into a JMP, version 7.01, statistical spreadsheet for analysis. Results A total of 89 patients with serviceable hearing had complete serial audiometric data available for analysis. The higher dose cohort included 43 patients treated to 50.4 Gy with a median follow-up (latest audiogram) of 53 weeks and the lower dose cohort included 46 patients treated to 46.8 Gy with a median follow-up of 65 weeks. The tumor control rate was 100% in both cohorts, and the pure tone average was significantly improved in the low-dose cohort (33 dB vs. 40 dB, p = 0.023, chi-square). When the patient data were analyzed at comparable follow-up points, the actuarial hearing preservation rate was significantly longer for the low-dose cohort than for the high-dose cohort (165 weeks vs. 79 weeks, p = .0318, log–rank). Multivariate analysis revealed the dose cohort ( p = 0.0282) and pretreatment Gardner-Robertson class ( p = 0.0215) to be highly significant variables affecting the hearing outcome. Conclusion A lower total dose at 46.8 Gy was associated with a 100% local control tumor rate and a greater hearing preservation rate. An additional dose reduction is justified to achieve the optimal dose that will yield the greatest hearing preservation rate without compromising tumor control for these patients.
42 citations
TL;DR: Baseline SQLI is a statistically significant determinant of survival and those who maintain independence have superior survival to those who are reliant on others, according to multivariate analysis.
Abstract: The Radiation Therapy Oncology Group (RTOG) embarked on a phase I/II study of patients suffering from glioblastoma multiforme (protocol 98-03) to assess the impact of dose escalation with 3-D conformal techniques. The primary endpoints were feasibility and survival. This report describes the outcome of secondary endpoints (quality of life and neurocognitive function). Patients with supratentorial GBM were treated with a combination of carmustine (BCNU) and conformal irradiation (dose levels: 66, 72, 78, 84 Gy, respectively). Quality of Life was assessed with the Spitzer Quality of Life Index. Neurocognitive function was determined by the Mini Mental Status Examination. The latter tests were administered at the start of irradiation, at the end of irradiation and then at 4 month intervals. Relatively high compliance was achieved with both of the tools (SQLI; MMSE). Overall rates of survival between baseline SQLI scores <7 and 7–10 were statistically significantly different [HR = 1.72, 95% CI (1.22, 2.4), P = 0.0015]. The significant impact of high SQLI score on survival was preserved in multivariate analysis. The component of this index which made the greatest contribution was the patient’s independence. There was continual deterioration of neurocognitive function within the populations studied. No correlation was seen between dose escalation and the secondary endpoints studied. Radiation dose escalation and assessment of its impact on life quality and neurocognition can be carried out in a large international trial. Baseline SQLI is a statistically significant determinant of survival. Those who maintain independence have superior survival to those who are reliant on others.
36 citations
TL;DR: Concurrent gemcitabine/paclitaxel chemoradiation regimen followed by adjuvant gemcitABine/carboplatin produced excessive toxicity at the lowest tested dose combination and was not suitable for further study in this trial.
19 citations
TL;DR: There was a marked decrease in the documented use of supportive care measures in the community setting, which may indicate an under appreciation and undertreatment of clinically significant acute tumor and treatment-related toxicities.
Abstract: Goals of work
We report the first analysis of demographic, socioeconomic, and toxicity data from the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).
18 citations
University of Texas MD Anderson Cancer Center1, University of Toronto2, Stanford University3, University of Groningen4, Harvard University5, University of California, San Francisco6, Memorial Sloan Kettering Cancer Center7, University of Rochester8, University of California, Los Angeles9, Thomas Jefferson University10
TL;DR: Major conclusions of the symposium were that the flow cytometry of multiple markers in fresh tissue would remain the standard technique of evaluating cancer-initiating cells and that surrogates need to be developed for both experimental and clinical use.
Abstract: At a meeting of the Translation Research Program of the Radiation Therapy Oncology Group held in early 2008, attendees focused on updating the current state of knowledge in cancer stem cell research and discussing ways in which this knowledge can be translated into clinical use across all disease sites. This report summarizes the major topics discussed and the future directions that research should take. Major conclusions of the symposium were that the flow cytometry of multiple markers in fresh tissue would remain the standard technique of evaluating cancer-initiating cells and that surrogates need to be developed for both experimental and clinical use.
10 citations
TL;DR: Puzzling a multiplicity of repair factors may be able to identify more than one prognostic factor that may be utilized in molecularly targeted therapy that might improve survival and QOL.
Abstract: Repair of DNA adducts appears to be an important mechanism in chemotherapy responsiveness in glioblastoma multiforme (GBM). Meta-analyses have suggested that the addition of chemotherapy increases the percentage of long-term survivors. Because GBM is characterized by multiplicity of pathways that characterize growth and treatment resistance, we hypothesized probing a multiplicity of repair factors may be able to identify more than one prognostic factor that may be utilized in molecularly targeted therapy that might improve survival and QOL. Seven DNA repair factors showed statistical significance when added to the initial logistic model of RPA class on length of survival status. After adjusting for RPA class the only statistically significant result of the multivariable logistic regressions for these 7 DNA repair factors was that as hMLH1-MF1 increased, the odds of being a short-term survivor versus a long-term survivor decreased (OR: 0.913, 95 per cent CI: 0.838-0.995, p=0.0385), multivariable analysis showed no associations between survival status and MGMT and p53 status, and the only statistically significant prognostic DNA repair factor was human Mut L Homologue 1 (hMLH1).
TL;DR: LorHAN demonstrates it is feasible to collect more detailed information about patient and tumor features and treatment other than surgery, and changes in the pattern of care and survival findings are expected to emerge as newer regimens are incorporated more broadly into clinical practice, and data in LORHAN matures.
Abstract: 6071 Background: Registries can be invaluable for describing patterns of care and outcomes for a population of patients (pts). We report the initial survival findings from LORHAN, a prospective, lo...
TL;DR: A 19-year-old South African white male with a medical history of intermittent migraines, believed this patient had a resolving aseptic (viral) meningitis and his symptoms were not attributable to a neuroma, as originally thought.
Abstract: A 19-year-old South African white male with a medical history of intermittent migraines, presented with a headache. The patient developed tongue paresthesias, progressive numbness, difficulty blinking, and then, complete right facial hemiparesis. Work-up at an emergency department showed a normal complete blood count, metabolic panel, sedimentation rate, a negative rapid plasma regain, and Lyme disease titer. He was diagnosed with Bell’s Palsy and was discharged with prednisone, acyclovir, and analgesics.
Over the next few weeks, the right-sided facial paralysis resolved, but his occipital headaches and posterior neck aches persisted. Three weeks after initial presentation, a brain magnetic resonance imaging (MRI) scan showed uniform enhancement and a soft tissue mass measuring 9 × 4 mm mass extending along the length of the right auditory canal consistent with a facial or acoustic neuroma. The area of enhancement extended from the porus acousticus to the apex of the internal auditory canal. No other abnormalities were noted. The patient was diagnosed with an acoustic neuroma and referred to the Radiation Oncology Department for stereotactic radiation therapy.
At that time, the patient’s main complaint was subjective residual right-sided weakness while blinking, fatigue, morning headache, and intermittent lightheadedness. His review of systems was positive only for a very mild, persistent dry cough subsequent to the development of the right-sided facial weakness. His physical examination did not reveal any localizing neurologic deficits.
Our review of the MRI (Figs. (Figs.11 and and2)2) showed the mass in the area of the porus acousticus and additional enhancement of the cavernous sinus, its associated cranial nerves, and both trigeminal nerves. Given these findings, the patient was referred for a lumbar puncture. Cerebrospinal fluid analysis showed normal glucose and angiotensin converting enzyme levels, and no monoclonal paraprotein spike. These tests showed elevated immunoglobulin G percent and elevated protein. Serum testing was negative for Venereal Disease Research Laboratory, monoclonal paraprotein spike, myelin basic protein, and bacterial growth.
FIGURE 1
MRI illustrating an abnormality in the cerebellopontine angle in the region of the seventh and eighth nerve (large arrow) and bilateral trigeminal nerve thickening (shorter arrows).
FIGURE 2
MRI illustrating an abnormality in the cerebellopontine angle in the region of the seventh and eighth nerve (large arrow) and bilateral trigeminal nerve thickening (shorter arrows).
Bell’s Palsy is an abrupt, isolated, unilateral, peripheral nerve paralysis without an identifiable cause.1,2 Generally speaking, Bell’s Palsy can be broadly divided into 3 etiologies: oncologic, autoimmune, and infectious (Table 1).3 In our minds, the strongest diagnostic possibilities were infectious meningitis or neoplastic (facial neuroma vs. acoustic neuroma).
TABLE 1
Causes of Bell’s Palsy
After comprehensive evaluation, we believed this patient had a resolving aseptic (viral) meningitis and his symptoms were not attributable to a neuroma, as originally thought. A repeat MRI at 3 months demonstrated complete resolution of the previous enhancing areas and the growth that originally showed as a soft tissue mass.
This interesting clinical presentation highlights the critical need by oncologists to fully consider other disease entities when evaluating these referred patients. For many patients with a presumed acoustic neuroma, biopsy is typically not done, and the patient is empirically treated with stereotactic radiation therapy based on clinical presentation and radiographic appearance. Oncologists should remember that “Therefore, go not to immediately irradiate, when the Bell’s Palsy tolls, but think carefully before treating when it does …”
Abstract: e20519 Background: Radiation Therapy Oncology Group 9402 compared PCV chemotherapy plus radiation therapy (PCV+RT) versus RT alone for anaplastic oligodendroglioma. Here we report 1) longitudinal changes in cognition and quality of life, 2) effects of patient factors and treatments on cognition, quality of life and survival, and 3) prognostic implications of cognition and quality of life. Methods: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL) by repeat assessments. Scores were analyzed for survivors and within five years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those dying within 5 years, MMSE scores were stable initially, while B-QOL scores decreased; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (P=0.0413 for MMSE; P=0.0016 for B-QO...
TL;DR: In this paper, a meta-analysis was conducted to determine the influence of gender, race, and marital status on overall survival (OS) in Radiation Therapy Oncology Group nonoperative non-small cell lung cancer trials.
Abstract: Objective: A meta-analysis was conducted to determine the influence of gender, race, and marital status on overall survival (OS) in Radiation Therapy Oncology Group nonoperative non-small cell lung cancer trials. Materials and Methods: Data from 1365 patients treated on nine prospective Radiation Therapy Oncology Group studies activated during the 1990s were analyzed. Impact of gender, marital status, and race was considered in the Cox proportional hazards models. Age, Karnofsky performance status, weight loss, stage, histology, location of primary tumor, biologic equivalent dose, deviation from protocol dose, and education level were adjusted in the model. A two-sided p value 0.05 was considered statistically significant. Results: Males had significantly higher mortality than females adjusted for other covariates (hazard ratio [HR] 1.22, 95% confidence interval 1.08–1.38). Race and marital status were not independently predictive for OS. Single females had significantly better OS than single males (HR 0.72), and married males had lower OS than single females (HR 1.36). Conclusions: These results suggest that although certain subgroups of gender, race, and/or marital status have better outcomes with respect to OS; gender seems to be the most significant factor influencing survival results among nonoperative non-small cell lung cancer patients.