Papers by JEFFREY BRADLEY
Radiotherapy and Oncology, 2020
Practical radiation oncology, Jan 10, 2018
Clinical concern remains regarding the relationship between consecutive (QD) versus nonconsecutiv... more Clinical concern remains regarding the relationship between consecutive (QD) versus nonconsecutive (QoD) lung stereotactic body radiation therapy (SBRT) treatment schedules and outcomes for clinical stage I non-small cell lung cancer (NSCLC). We examined a multi-institutional series of patients receiving 5-fraction lung SBRT to compare the local failure rates and overall survival between patients receiving QD versus QoD treatment. Lung SBRT databases from 2 high-volume institutions were combined, and patients receiving 5-fraction SBRT for a solitary stage I NSCLC were identified. QD treatment was defined as completing SBRT in ≤7 days, whereas QoD treatment was defined as completing treatment in >7 days. To control for patient characteristics between the 2 institutions, a 1:1 propensity-matched analysis was performed. Multivariable logistic regression was performed to identify variables independently associated with local failure, and Cox proportional hazards modeling to identify ...
Journal of applied clinical medical physics, Mar 8, 2016
The purpose of this study is to describe the comprehensive commissioning process and initial clin... more The purpose of this study is to describe the comprehensive commissioning process and initial clinical experience of the Mevion S250 proton therapy system, a gantry-mounted, single-room proton therapy platform clinically implemented in the S. Lee Kling Proton Therapy Center at Barnes-Jewish Hospital in St. Louis, MO, USA. The Mevion S250 system integrates a compact synchrocyclotron with a C-inner gantry, an image guidance system and a 6D robotic couch into a beam delivery platform. We present our commissioning process and initial clinical experience, including i) CT calibration; ii) beam data acquisition and machine characteristics; iii) dosimetric commissioning of the treatment planning system; iv) validation through the Imaging and Radiation Oncology Core credentialing process, including irradiations on the spine, prostate, brain, and lung phantoms; v) evaluation of localization accuracy of the image guidance system; and vi) initial clinical experience. Clinically, the system opera...
International journal of radiation oncology, biology, physics, 2016
Lung Cancer, 2010
To describe early and late CT patterns of radiographic lung injury after SBRT for lung cancer, an... more To describe early and late CT patterns of radiographic lung injury after SBRT for lung cancer, and to correlate radiological findings with patient and treatment characteristics. Follow-up CT scans of 68 patients with 70 tumors were divided into 4 periods: (1) 6 weeks; (2) 2-6 months; (3) 7-12 months and (4) 13-18 months after SBRT. Early (within 6 months) and late radiological injuries were evaluated according to Ikezoe and Koening, respectively. The correlation between CT findings and patient characteristics was evaluated. Radiographic injury in periods 1 and 2 was: (1) diffuse consolidation 3 and 27%, (2) patchy consolidation and ground-glass opacity (GGO) 13.2 and 33%, (3) diffuse GGO 13.2 and 21%, (4) patchy GGO 16.2 and 6%, and (5) no findings 54.4 and 21%, respectively. Late injury in periods 3 and 4 were: (1) modified conventional pattern (consolidation, volume loss, bronchiectasis) 54 and 44%, (2) mass-like 20 and 28%, (3) scar-like 14 and 16% and (4) no findings 20 and 12%, respectively. The proportion of emphysema grades 2-4 was significantly higher in patients who had no radiological findings 6 weeks after treatment (p=0.021). Both patchy consolidation and GGO patterns resulted more frequently in patients who were not administered steroids (p=0.035). No relationship was found with smoking, tumor dimension and radiation dose. The majority of patients had no evidence of radiographic lung injury 6 weeks after SBRT; the most prevalent findings were diffuse or patchy GGO. Patchy and diffuse consolidation develops 2-6 months after SBRT. Modified conventional pattern was the most prevalent in the late periods.
Clinical Lung Cancer, 2014
Background-The addition of targeted agents to thoracic radiation has not improved outcomes in pat... more Background-The addition of targeted agents to thoracic radiation has not improved outcomes in patients with locally advanced non-small cell lung cancer (NSCLC). In order to improve cure rates in locally advanced NSCLC, effective targeted therapies need to be identified that can be given safely with radiation therapy. Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway and has single agent activity in lung cancer. Inhibition of the mTOR pathway has been shown to augment the cytotoxic effect of radiation in preclinical studies. There is scant clinical experience with mTOR inhibitors and radiation. Methods-We performed a phase I study evaluating the combination of temsirolimus with thoracic radiation in patients with NSCLC. Results-Ten patients were enrolled in the study. The dose limiting toxicities included sudden death, pneumonitis and pulmonary hemorrhage. The maximum tolerated dose of temsirolimus that could be administered safely with concurrent radiotherapy (35 Gy in 14 daily fractions) was 15 mg intravenously weekly. Of the 8 evaluable patients, 3 had a partial response and 2 had stable disease. Conclusion-The combination of temsirolimus 15 mg weekly and thoracic radiation is welltolerated and warrants further investigation, perhaps in a molecularly defined subset of patients.
Seminars in Radiation Oncology, 2004
Radiation esophagitis remains the primary dose-limiting acute toxicity in the radiotherapeutic ma... more Radiation esophagitis remains the primary dose-limiting acute toxicity in the radiotherapeutic management of thoracic neoplasms. Improved understanding of this toxicity will facilitate dose escalation and enhancement of the therapeutic ratio. This article reviews the predictive factors and preventive strategies for radiation esophagitis. In particular, clinical and dosimetric studies predicting the risk of radiation esophagitis are analyzed. The critical impact of chemotherapy on radiation esophagitis is characterized. Preventive strategies to minimize this toxicity also are explored. Overall, this article reviews the current understanding of radiation toxicity for the esophagus.
Medical Physics, 2012
Phase-binning algorithms are commonly utilized in 4DCT image reconstruction for characterization ... more Phase-binning algorithms are commonly utilized in 4DCT image reconstruction for characterization of tumor or organ shape and respiration motion, but breathing irregularities occurring during 4DCT acquisition can cause considerable image distortions. Recently, amplitude-binning algorithms have been evaluated as a potential improvement to phase-binning algorithms for 4DCT image reconstruction. The purpose of this study was to evaluate the performance of the first commercially available on-line retrospective amplitude-binning algorithm for comparison to the traditional phase-binning algorithm. Methods: Both phantom and clinical data were used for evaluation. A phantom of known geometry was mounted on a 4D motion platform programmed with seven respiratory waves (two computer generated and five patient trajectories) and scanned with a Philips Brilliance Big bore 16-slice CT simulator. 4DCT images were reconstructed using commercial amplitude-and phase-binning algorithms. Image quality of the amplitude-and phase-binned image sets was compared by evaluation of shape and volume distortions in reconstructed images. Clinical evaluations were performed on 64 4DCT patient image sets in a blinded review process. The amplitude-and phase-binned 4DCT maximum intensity projection (MIP) images were further evaluated for 28 stereotactic body radiation therapy (SBRT) cases of total 64 cases. A preliminary investigation of the effects of respiratory amplitude and pattern irregularities on motion artifact severity was conducted. Results: The phantom experiments illustrated that, as expected, maximum inhalation occurred at the 0% amplitude and maximum exhalation occurred at the 50% amplitude of the amplitude-binned 4DCT image sets. The phantom shape distortions were more severe in the images reconstructed from the phase-binning algorithm. In the clinical study, compared to the phase-binning algorithm, the amplitude-binning algorithm yielded fewer or less severe motion artifacts in 37.5% of the cases (24=64), comparable artifacts in 54.7% of the cases (35=64), and slightly greater artifacts in 7.8% of the cases (5=64). Evaluation of SBRT cases demonstrated that the reconstructed tumor sizes and locations were comparable in 96% (1=28) of the MIP image pairs generated from both amplitudeand phase-binning algorithms. In this case the amplitude-binned image set rendered a smaller tumor size, which was likely due to very shallow respiratory amplitudes occurring over several breathing cycles. Conclusions: Overall, the amplitude-binning algorithm for 4DCT reconstruction reduced the severity of tumor distortion and image artifacts compared to the phase-binning algorithm. However, the full range of motion may not be characterized using amplitude-binning algorithms. Despite superior performance, amplitude binning can still be susceptible to motion artifacts caused by large variations in amplitude of respiratory waves. V
Journal of Thoracic Oncology, 2008
Introduction: To determine the prognostic value of celiac lymphadenopathy for patients with esoph... more Introduction: To determine the prognostic value of celiac lymphadenopathy for patients with esophageal or gastroesophageal junction carcinomas treated with neoadjuvant or definitive chemoradiotherapy. Methods: The records of patients undergoing chemoradiation therapy for esophageal cancer, who received a dose of at least 45 Gy, were retrospectively reviewed. Results: One hundred forty-four patients were eligible for this retrospective analysis; 99 had M0 and 45 M1a disease. The median radiation dose was 50.4 Gy for patients receiving both neoadjuvant and definitive chemoradiotherapy. After a median follow-up of 15 months, the 2-year overall survival for the entire cohort was 45% and 20% in M0 and M1a groups, respectively (p Ͻ 0.001). On multivariate analysis, the most significant factors for overall survival were performance status (p Ͻ 0.001) and M1a status (p Ͻ 0.001). The patients who underwent definitive concomitant chemoradiation had a 2-year overall survival of 36% and 15% in M0 and M1a, respectively (p ϭ 0.03). For patients who underwent neoadjuvant chemoradiation followed by surgery, the 2-year overall survival was 63% and 37% in M0 and M1a, respectively (p ϭ 0.07). Conclusions: M1a status is a strong predictor of poor outcome for patients with cancers of the esophagus or gastroesophageal junction. For patients receiving concurrent chemotherapy and radiation therapy for M1a esophageal cancer, treatment is largely palliative.
Journal of Thoracic Oncology, 2007
A 60-year-old African-American man with a long history
Journal of Thoracic Oncology, 2007
overall survival of 26(41%) patients with L.D was 12 months (range (3-21), and of 6(46%) patients... more overall survival of 26(41%) patients with L.D was 12 months (range (3-21), and of 6(46%) patients with E.D was 9 months. Median survival of the remaining 44(58%) patients, (37(59%) with L.D and 7 patients with E.D), with palliative treatment was 2 months in each stage. Difference according to treatment is statistically significant (p= 0,0055) Median Survival from diagnosis of patients with L.D with weight loss less than 10% was 11 months and with E.D 2 months (p<0,001). Median survival from diagnosis with more than 10% with L.D was 3 months and with E.D 2 months, difference statistically significant (p, 0003), Log Rank 13,22 1. Median survival from CTRT with L.D was 16 months and with E.D 9 months (p=.0295). Median survival from diagnosis with KPS less than 70% in patients with L.D was 5 months and E.D 2 months. and median survival from CTRT with L.D was 6 months and median survival with KPS more than 70% in LD was 8 months, while in E.D 4 months (p=0.004). Median survival from CTRT in L.D was 16 months Range (10-22) and with E.D 9 months difference statistically significant (p=.0395) 33% of the patients with, weight loss more than 10% and KPS with less than 70% and extension of disease, explains the poor prognosis and low survival of this setting. Comparing 6% patients with SCLC of this hospital population, means that about 14%(160 patients) and about other 37 patients with E.D, were managed elsewhere. Furthermore 59% of patients with L.D of this series did not receive CTRT mostly for costs. Conclusions: Selection of patients for treatment with these prognostic factors was not enough to improve survival of LC patients in our community. The voluntary lung cancer database registry made possible to measure the epidemiology, treatment and follow-up of patients with NSCLC and SCLC of the INT. Thus, this system and a national database registry for cancer patients, should be useful for better service medicine, clinical research and improve patient care in most developing countries.
Journal of Thoracic Oncology, 2009
I n this issue of the Journal of Thoracic Oncology, Stephans et al. from the Cleveland Clinic rep... more I n this issue of the Journal of Thoracic Oncology, Stephans et al. from the Cleveland Clinic report their review of pulmonary function testing (PFT) before and after stereotactic body radiation therapy (SBRT) for stage I lung cancer. 1 Though retrospective, this contribution is meaningful. The "believers" know that SBRT offers a substantial improvement in local control with relatively little toxicity compared with conventionally fractionated radiation therapy for these medically inoperable patients. The "skeptics" are fearful that the delivery of such high doses of radiation therapy may not be safe in the long run for this frail patient population. Stephans et al. show data that are consistent with two other datasets, that forced expiratory volume in 1 second FEV 1 % and diffusing capacity of the lung for carbon monoxide remain relatively unchanged following SBRT. 2,3 Local control rates of 85 to 90% are now expected with SBRT for T1-2N0 lung cancers, provided that biologic equivalent doses of Ͼ100 Gy are employed. 4 Multiple radiation oncology centers from around the world using multiple delivery technologies have demonstrated this level of effectiveness. 5-8 These individual centers have also reported acute and late toxicities, which have been low (Յ5%). Until recently, there has been a paucity of data showing the effect of SBRT on PFT. Prospective trials may lend validity to these results. Phase I/II prospective studies have recently been completed by the Radiation Therapy Oncology Group (RTOG 0236) 9 and Japanese Cooperative Oncology Group (JCOG 0403). Results from these trials are pending. A phase III randomized trial comparing SBRT to surgery is just underway for operable patients in The Netherlands (ROSEL trial). Further prospective studies evaluating SBRT for lung cancer are either ongoing or are being planned. Completion of these trials is important to verify these results in a multicenter setting and to promote the option of SBRT to pulmonologists, medical oncologists, and surgeons who also manage these patients. Looking more closely at the current manuscript, a few questions are raised that need further evaluation from others. Are there patients with PFT results that are too low to be treated with SBRT? Are patients with central tumors more apt to experience decline in PFTs (i.e., due to centrally located fibrosis or atelectasis)? Does a higher conformality index really result in greater PFT decline? These are important questions that often arise but remain unknown. Stephans et al. report a patient with an FEV 1 % as low as 15% who is locally controlled and without complications. Larger multicenter databases may provide a larger set of patients on which to base a PFT threshold. Of the 10 patients treated for centrally located tumors, no PFT difference has yet been encountered, though they were treated with a gentler dosing schedule. The RTOG just initiated a separate SBRT trial for patients with centrally located tumors (RTOG 0813). The intent of the RTOG trial is to determine the maximum tolerated dose to a bronchus using five fractions, and to determine the effectiveness of that dose. Also in the current dataset, a higher conformality index resulted in greater PFT loss, implying that there may be a threshold for the number of beams used above which the low-dose volume becomes too high. What should the 5 Gy isodose volume be limited to? As the number of beams increases, so does the 5 Gy isodose volume. This has implications for SBRT planning and delivery.
Journal of Thoracic Oncology, 2010
Trovo et al. undertook a retrospective review of 144 patients with esophageal cancer treated at W... more Trovo et al. undertook a retrospective review of 144 patients with esophageal cancer treated at Washington University who received neoadjuvant or definitive chemoradiation. They sought to determine the prognostic value of celiac lymph node metastases. As the management in these patients is controversial, we commend the authors for contributing to the literature on this important subset of patients. However, we respectfully wish to clarify and comment on the data, as well as their conclusions, as presented in the recent article in the Journal of Thoracic Oncology. 1 Some clinicians believe that the presence of M1a disease, similar to T4 disease or distant metastases, precludes curative treatment approaches. The present report by Trovo et al. documented reasonably good survival outcomes for a cohort of patients for whom survival outcomes are often considered to be quite dismal. For instance, the 2and 5-year overall survival was 36% and 15% in the M0 and 15% and 11% in M1a groups, respectively (p ϭ 0.03). For patients undergoing neoadjuvant chemoradiation, the 2-and 5-year overall survival was 63% and 36% in the M0 and 37% and 13% in the M1a groups, respectively (p ϭ 0.07). The authors state that M1a status is a strong predictor of poor outcome, and thus, treatment should be considered largely palliative. According to the authors, the American Joint Committee on Cancer staging system for esophageal carcinoma divides the M classification into M1a and M1b categories.
The Journal of Thoracic and Cardiovascular Surgery, 2013
The purpose of the present study was to compare the selection criteria and short-term outcomes am... more The purpose of the present study was to compare the selection criteria and short-term outcomes among 3 prospective clinical trials using stereotactic body radiotherapy (Radiation Therapy Oncology Group [RTOG] trial 0236), sublobar resection (American College of Surgeons Oncology Group [ACOSOG] trial Z4032), and radiofrequency ablation (ACOSOG trial Z4033). Methods: The selection criteria and outcomes were compared among RTOG 0236 (n ¼ 55), ACOSOG Z4032 (n ¼ 211), and ACOSOG Z4033 (n ¼ 51). Age, Eastern Cooperative Oncology Group performance status, percentage of predicted forced expiratory volume in 1 second, and percentage of predicted carbon monoxide diffusing capacity of the lung were used to perform a propensity-matched analysis among patients with clinical stage 1A in RTOG 0236 and ACOSOG Z4032. Results: The patients in ACOSOG Z4033 undergoing radiofrequency ablation were older (75.6 AE 7.5 years) than those in RTOG 0236 (72.5 AE 8.8 years) and ACOSOG Z4032 (70.2 AE 8.5 years; P ¼ .0003). The pretreatment percentage of predicted forced expiratory volume in 1 second was 61.3% AE 33.4% for RTOG 0236, 53.8% AE 19.6% for ACOSOG Z4032, and 48.8% AE 20.3% for ACOSOG Z4033 (P ¼ .15). The pretreatment percentage of predicted carbon monoxide diffusing capacity of the lung was 61.6% AE 30.2% for RTOG 0236, 46.4% AE 15.6% for ACOSOG Z4032, and 43.7% AE 18.0% for ACOSOG Z4033 (P ¼ .001). The overall 90-day mortality for stereotactic body radiotherapy, surgery, and radiofrequency ablation was 0%, 2.4% (5/211), and 2.0% (1/51), respectively (P ¼ .5). Overall, the unadjusted 30-day grade 3þ adverse events were more common with surgery than with stereotactic body radiotherapy (28% vs 9.1%, P ¼ .004), although no difference was between the 2 groups at 90 days. Among the patients with clinical stage IA in ACOSOG Z4032, 29.3% had a more advanced pathologic stage at surgery. A propensity-matched comparison showed no difference between stereotactic body radiotherapy and surgery for 30-day grade 3þ adverse events (odds ratio, 2.37; 95% confidence interval, 0.75-9.90; P ¼ .18). Conclusions: Among appropriately matched patients, no difference was seen in early morbidity between sublobar resection and stereotactic body radiotherapy. These results underscore the need for a randomized trial to delineate the relative survival benefit of each modality and to help stratify patients considered high risk.
The Journal of Thoracic and Cardiovascular Surgery, 2014
Objectives: Comparative studies of survival between stereotactic body radiation therapy (SBRT) an... more Objectives: Comparative studies of survival between stereotactic body radiation therapy (SBRT) and surgery have been limited by lack of comparisons of recurrence patterns between matched cohorts in nonÀsmall cell lung cancer (NSCLC). Methods: All patients undergoing treatment with surgery or SBRT for clinical stage I NSCLC between June 2004 and December 2010 were reviewed. Age, tumor characteristics, comorbidity score, pulmonary function, overall survival (OS), disease-free survival (DFS), and recurrence data were collected and propensity matching performed. Results: The mean age for surgery (n ¼ 458) was 65.8 AE 10.5 versus 74.4 AE 9.4 for SBRT (n ¼ 151) (P<.0001). For the entire surgical cohort, 3-year OS was 78% and DFS was 72%. For the entire SBRT cohort, 3-year OS was 47% and DFS was 42%. The overall local recurrence rate for surgery was 2.6%. The overall local recurrence rate for SBRT was 10.7%. A propensity-matched comparison based on age, tumor size, Adult Comorbidity Evaluation comorbidity score, forced expiratory volume in the first second of expiration, and tumor location resulted in 56 matched pairs. The 3-year OS was 52% versus 68% for SBRT and surgery (P ¼ .05); DFS was 47% versus 65% (P ¼ .01). At 3 years, local recurrence-free survival was 90% versus 92% for SBRT and surgery (P ¼ .07). Conclusions: Although surgical resection seems to result in better OS and DFS versus SBRT, matching these disparate cohorts of patients remains challenging. Participation in clinical trials is essential to define the indications and relative efficacy of surgery and radiation therapy in a high-risk population with stage I NSCLC.
Journal of Clinical Oncology, 2008
Purpose Two nonoperative approaches (one without fluorouracil) using induction chemotherapy and t... more Purpose Two nonoperative approaches (one without fluorouracil) using induction chemotherapy and then definitive chemoradiotherapy developed at two centers were compared in patients with localized esophageal cancer (LEC). The primary end point was to assess whether any approach would achieve a ≥ 77.5% 1-year survival rate, surpassing the historical 66% rate from the Radiation Therapy Oncology Group (RTOG) protocol 9405. Patients and Methods In a multi-institutional cooperative group setting, patients with LEC who had unresectable cancer, were unwilling to undergo surgery, or were medically unfit for surgery were randomly assigned to receive either induction with fluorouracil, cisplatin, and paclitaxel and then fluorouracil plus paclitaxel with 50.4 Gy of radiation (arm A) or induction with paclitaxel plus cisplatin and then the same chemotherapy with 50.4 Gy of radiation (arm B). Safety and survival rates were assessed. Results A total of 84 patients were randomly assigned (arm A, n ...
International Journal of Radiation Oncology*Biology*Physics, 2013
To identify deficiencies with simulation and treatment planning orders and to develop corrective ... more To identify deficiencies with simulation and treatment planning orders and to develop corrective measures to improve safety and quality. At Washington University, the DMAIIC formalism is used for process management, whereby the process is understood as comprising Define, Measure, Analyze, Improve, Implement, and Control activities. Two complementary tools were used to provide quantitative assessments: failure modes and effects analysis and reported event data. The events were classified by the user according to severity. The event rates (ie, number of events divided by the number of opportunities to generate an event) related to simulation and treatment plan orders were determined. We analyzed event data from the period 2008-2009 to design an intelligent SIMulation and treatment PLanning Electronic (SIMPLE) order system. Before implementation of SIMPLE, event rates of 0.16 (420 of 2558) for a group of physicians that were subsequently used as a pilot group and 0.13 (787 of 6023) for all physicians were obtained. An interdisciplinary group evaluated and decided to replace the Microsoft Word-based form with a Web-based order system. This order system has mandatory fields and context-sensitive logic, an ability to create templates, and enables an automated process for communication of orders through an enterprise management system. After the implementation of the SIMPLE order, the event rate decreased to 0.09 (96 of 1001) for the pilot group and to 0.06 (145 of 2140) for all physicians (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). The average time to complete the SIMPLE form was 3 minutes, as compared with 7 minutes for the Word-based form. The number of severe events decreased from 10.7% (45 of 420) and 12.1% (96 of 787) to 6.2% (6 of 96) and 10.3% (15 of 145) for the pilot group and all physicians, respectively. There was a dramatic reduction in the total and the number of potentially severe events through use of the SIMPLE system. In addition, the order process has become more efficient and reliable.
International Journal of Radiation Oncology*Biology*Physics, 2008
Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 9... more Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm 3) vs. larger (>45 cm 3
International Journal of Radiation Oncology*Biology*Physics, 2005
To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensio... more To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer. A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 Gy with the treatment plan (V(20)). Patients with a V(20) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25% (Group 1) received 70.9 Gy in 33 fractions, 77.4 Gy in 36 fractions, 83.8 Gy in 39 fractions, and 90.3 Gy in 42 fractions, successively. Patients with a V(20) of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V(20) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method. The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V(20). The estimated rate of late Grade 3 or worse esophageal toxicity at 18 months was 8%, 0%, 4%, and 6%, for Group 1 patients receiving 70.9, 77.4, 83.8, 90.3 Gy, respectively, and 0% and 5%, respectively, for Group 2 patients receiving 70.9 and 77.4 Gy. The dyspnea index scoring at baseline and after therapy for functional impairment, magnitude of task, and magnitude of effort revealed no change in 63%, functional pulmonary loss in 23%, and pulmonary improvement in 14% of patients. The observed locoregional control and overall survival rates were each similar among the study arms within each dose level of Groups 1 and 2. Locoregional control was achieved in 50-78% of patients. Thirty-one patients developed regional nodal failure. The location of nodal failure in relationship to the RT volume was documented in 28 of these 31 patients. Twelve patients had isolated elective nodal failures. Fourteen patients had regional failure in irradiated nodal volumes. Two patients had both elective nodal and irradiated nodal failure. The radiation dose was safely escalated using three-dimensional conformal techniques to 83.8 Gy for patients with V(20) values of…
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Papers by JEFFREY BRADLEY