To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology ... more To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.
To report the application of an adaptive replanning technique for prostate cancer radiotherapy (R... more To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. The new "SAM+SWO" scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 +/- 2 minutes. The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT.
To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity afte... more To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. All patients were treated with external beam radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity was graded according to the Common Toxicity Criteria Version 2.0, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used for all other toxicity. A total of 138 patients from 28 institutions were entered on this study. Acute toxicity information was available in 131 patients, and 127 patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed. The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5 toxicity has been observed. The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience.
The purpose of this work is to explore a new adaptive radiation therapy (ART) strategy, combined ... more The purpose of this work is to explore a new adaptive radiation therapy (ART) strategy, combined "online and offline" ART, that can fully account for interfraction variations similar to the existing online ART but with substantially reduced online effort. The concept for the combined ART is to perform online ART only for the fractions with obvious interfraction variations and to deliver the ART plan for that online fraction as well as the subsequent fractions until the next online fraction needs to be adapted. To demonstrate the idea, the daily computed tomographic (CT) data acquired during image guided radiation therapy (IGRT) with an in-room CT (CTVision, Siemens Healthcare, Amarillo, TX) for 6 representative patients (including 2 prostate, 1 head-and-neck, and 1 pancreatic cancer, 1 adrenal carcinoma, and 1 craniopharyngioma patients) were analyzed. Three types of plans were generated based on the following selected daily CTs: (1) IGRT repositioning plan, generated by applying the repositioning shifts to the original plan (representing the current IGRT practice); (2) Re-Opt plan, generated with full-scope optimization; and (3) ART plan, either online ART plan generated with an online ART tool (RealArt, Prowess Inc, Concord, CA) or offline ART plan generated with shifts from the online ART plan. Various dose-volume parameters were compared with measure dosimetric benefits of the ART plans based on daily dose distributions and the cumulative dose maps obtained with deformable image registration. In general, for all the cases studied, the ART (with 3-5 online ART) and Re-Opt plans provide comparable plan quality and offer significantly better target coverage and normal tissue sparing when compared with the repositioning plans. This improvement is statistically significant. The combined online and offline ART is dosimetrically equivalent to the online ART but with substantially reduced online effort, and enables immediate delivery of the adaptive plan when an obvious anatomic change is observed.
We describe a four-year experience with bone marrow transplantation involving closely HLA-matched... more We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.
To quantify interfractional anatomic variations and limitations of the current practice of image-... more To quantify interfractional anatomic variations and limitations of the current practice of image-guided radiation therapy (IGRT) for prostate-bed patients and to study dosimetric benefits of an online adaptive replanning scheme that addresses the interfractional variations. Contours for the targets and organs at risk (OARs) from daily diagnostic-quality CTs acquired with in-room CT (CTVision, Siemens) were generated by populating the planning contours using an autosegmentation tool based on deformable registration (ABAS, Elekta) with manual editing for ten prostate-bed patients treated with postoperative daily CT-guided IMRT. Dice similarity coefficient (DSC) obtained by maximizing the overlap of contours for a structure between the daily and plan contours was used to quantify the organ deformation between the plan and daily CTs. Three interfractional-variation-correction schemes, the current standard practice of IGRT repositioning, a previously developed online adaptive RT (ART), and the full reoptimization, were applied to these daily CTs and a number of dose-volume quantities for the targets and organs at risk were compared for their effectiveness to account for the interfractional variations. Large interfractional organ deformations in prostate-bed irradiation were seen. The mean DSCs for CTV, rectum, and bladder were 86.6 ± 5.1% (range from 61% to 97%), 77.3% ± 7.4% (range from 55% to 90%), and 75.4% ± 11.2% (range from 46% to 96%), respectively. The fractional and cumulative dose-volume quantities for CTV and PTV: V100 (volume received at least 100% prescription dose), and rectum and bladder: V45Gy and V60Gy (volume received at least 45 or 60 Gy), were compared for the repositioning, adaptive, reoptimization, and original plans. The fractional and cumulative dosimetric results were nearly the same. The average cumulative CTV V100 were 88.0%, 98.4%, 99.2%, and 99.3% for the IGRT, ART, reoptimization, and original plans, respectively. The corresponding rectal V45Gy (V60Gy) were 58.7% (27.3%), 48.1% (20.7%), 43.8% (16.1%), and 44.9% (16.8%). The results for bladder were comparable among three schemes. Paired two-tailed Wilcoxon signed-rank tests were performed and it was found that ART and reoptimization provide better target coverage and better OAR sparing, especially rectum sparing. The interfractional organ motions and deformations during prostate-bed irradiation are significant. The online adaptive replanning scheme is capable of effectively addressing the large organ deformation, resulting in cumulative doses equivalent to those originally planned.
To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for pa... more To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT). Prostate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms. At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P <or= .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein. LTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.
Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate... more Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results. Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF). Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.
International Journal of Radiation Oncology*Biology*Physics, 1998
The purpose of this study was to assess response, toxicity, failure patterns, and survival differ... more The purpose of this study was to assess response, toxicity, failure patterns, and survival differences in three chemotherapy (ChT)/radiation therapy (RT) sequencing strategies for locally advanced non-small cell lung cancer (NSCLC). Five completed Radiation Therapy Oncology Group (RTOG) trials for Stage II-IIIA/B inoperable NSCLC patients employed one of the three following strategy groupings: 1) sequential ChT followed by standard RT (60 Gy in 6 weeks); 2) combined sequential and concurrent ChT and standard RT (60 Gy in 6 weeks); or 3) concurrent ChT and hyperfractionated RT (69.6 Gy in 6 weeks). All five trials required KPS > or = 70; two trials (314 patients) required <5% weight loss and three trials (147 patients) had no minimum weight loss requirement. In all five trials the ChT used cisplatin with either vinblastine or oral etoposide. Combining data for the five trials yielded an evaluable group of 461 patients. The three methods of sequencing ChT and RT were evaluated for differences in response, acute and late toxicity, patterns of failure, and survival. Acute toxicity was defined as that occurring within 90 days from the start of RT. Late toxicity was defined as that occurring after 90 days from the start of RT. Acute or late toxicity > or = grade 3 was defined as severe. Site of first failure was recorded by date. In-field failure excluded distant metastasis as a failure and included only tissue in the RT treatment field. Overall progression-free survival (PFS) was defined as survival without evidence of intra- or extrathoracic tumor or death from any cause. Group 1 had a lower overall response rate (63%) compared to either Group 2 (77%) or Group 3 (79%), p = 0.03 and 0.003, respectively. Overall grade 4/5 acute toxicities were nearly equal between groups. The severe nonhematologic acute toxicities were significantly different by strategy group (p < 0.0001). Group 1 and 2 were not statistically different. Group 3 had significantly more patients with severe acute nonhematologic toxicity (55%) than either Group 1 (27%) or 2 (34%) with p < 0.0001 and p = 0.0005, respectively. This was due to a severe acute esophagitis rate of 34% for Group 3 versus 1.3% for Group 1 and 6% for Group 2 (p < 0.0001 for both comparisons). Overall grade 4/5 late toxicities did not differ by group. Severe late nonhematologic toxicities were different by group (p = 0.0098). Group 1 patients had significantly fewer severe late nonhematologic toxicities (14%) compared to patients in Groups 2 (26%) or 3 (28%) (p = 0.046 and 0.038, respectively). Severe late lung toxicity was 10% for Group 1 compared to 21% and 20% for Groups 2 and 3, respectively. Severe late lung toxicities differed by group (p = 0.033), but not severe late esophagitis (p = 0.077). There were no differences between the three strategy groups for patterns of first failure. The in-field failures were higher in Group 2 (71%) compared to Groups 1 (56%) and 3 (55%), p = 0.0478. Pairwise comparisons yielded p-values of 0.068 and 0.015 for Group 2 versus 1 and Group 2 versus 3, respectively. Three-year PFS was better in Group 2 (15%) and 3 (15%) compared to Group 1 (7%), but not statistically significant (p = 0.454). Similarly, in-field PFS was better in Group 2 (17%) and 3 (20%) than Group 1 (9%), but not significant (p = 0.167). There were improvements in 3-year survival for Group 2 (17%) and Group 3 (25%) compared to Group 1 (15%), but the differences were not statistically significant (p = 0.47). The same results were present for patients with less than 5% weight loss and patients with stage IIIA tumors. Thus, concurrent ChT and hyperfractionated RT had a higher incidence of severe acute esophageal toxicity. Severe late lung toxicity with concurrent ChT/hyperfractionated RT, as well as with induction ChT followed by concurrent ChT/standard RT, may be greater compared to sequential ChT/RT. (ABSTRACT TRUNCATED)
International Journal of Radiation Oncology*Biology*Physics, 2006
To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity afte... more To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. All patients were treated with external beam radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity was graded according to the Common Toxicity Criteria Version 2.0, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used for all other toxicity. A total of 138 patients from 28 institutions were entered on this study. Acute toxicity information was available in 131 patients, and 127 patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed. The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5 toxicity has been observed. The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience.
To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology ... more To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.
To report the application of an adaptive replanning technique for prostate cancer radiotherapy (R... more To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. The new "SAM+SWO" scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 +/- 2 minutes. The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT.
To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity afte... more To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. All patients were treated with external beam radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity was graded according to the Common Toxicity Criteria Version 2.0, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used for all other toxicity. A total of 138 patients from 28 institutions were entered on this study. Acute toxicity information was available in 131 patients, and 127 patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed. The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5 toxicity has been observed. The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience.
The purpose of this work is to explore a new adaptive radiation therapy (ART) strategy, combined ... more The purpose of this work is to explore a new adaptive radiation therapy (ART) strategy, combined "online and offline" ART, that can fully account for interfraction variations similar to the existing online ART but with substantially reduced online effort. The concept for the combined ART is to perform online ART only for the fractions with obvious interfraction variations and to deliver the ART plan for that online fraction as well as the subsequent fractions until the next online fraction needs to be adapted. To demonstrate the idea, the daily computed tomographic (CT) data acquired during image guided radiation therapy (IGRT) with an in-room CT (CTVision, Siemens Healthcare, Amarillo, TX) for 6 representative patients (including 2 prostate, 1 head-and-neck, and 1 pancreatic cancer, 1 adrenal carcinoma, and 1 craniopharyngioma patients) were analyzed. Three types of plans were generated based on the following selected daily CTs: (1) IGRT repositioning plan, generated by applying the repositioning shifts to the original plan (representing the current IGRT practice); (2) Re-Opt plan, generated with full-scope optimization; and (3) ART plan, either online ART plan generated with an online ART tool (RealArt, Prowess Inc, Concord, CA) or offline ART plan generated with shifts from the online ART plan. Various dose-volume parameters were compared with measure dosimetric benefits of the ART plans based on daily dose distributions and the cumulative dose maps obtained with deformable image registration. In general, for all the cases studied, the ART (with 3-5 online ART) and Re-Opt plans provide comparable plan quality and offer significantly better target coverage and normal tissue sparing when compared with the repositioning plans. This improvement is statistically significant. The combined online and offline ART is dosimetrically equivalent to the online ART but with substantially reduced online effort, and enables immediate delivery of the adaptive plan when an obvious anatomic change is observed.
We describe a four-year experience with bone marrow transplantation involving closely HLA-matched... more We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.
To quantify interfractional anatomic variations and limitations of the current practice of image-... more To quantify interfractional anatomic variations and limitations of the current practice of image-guided radiation therapy (IGRT) for prostate-bed patients and to study dosimetric benefits of an online adaptive replanning scheme that addresses the interfractional variations. Contours for the targets and organs at risk (OARs) from daily diagnostic-quality CTs acquired with in-room CT (CTVision, Siemens) were generated by populating the planning contours using an autosegmentation tool based on deformable registration (ABAS, Elekta) with manual editing for ten prostate-bed patients treated with postoperative daily CT-guided IMRT. Dice similarity coefficient (DSC) obtained by maximizing the overlap of contours for a structure between the daily and plan contours was used to quantify the organ deformation between the plan and daily CTs. Three interfractional-variation-correction schemes, the current standard practice of IGRT repositioning, a previously developed online adaptive RT (ART), and the full reoptimization, were applied to these daily CTs and a number of dose-volume quantities for the targets and organs at risk were compared for their effectiveness to account for the interfractional variations. Large interfractional organ deformations in prostate-bed irradiation were seen. The mean DSCs for CTV, rectum, and bladder were 86.6 ± 5.1% (range from 61% to 97%), 77.3% ± 7.4% (range from 55% to 90%), and 75.4% ± 11.2% (range from 46% to 96%), respectively. The fractional and cumulative dose-volume quantities for CTV and PTV: V100 (volume received at least 100% prescription dose), and rectum and bladder: V45Gy and V60Gy (volume received at least 45 or 60 Gy), were compared for the repositioning, adaptive, reoptimization, and original plans. The fractional and cumulative dosimetric results were nearly the same. The average cumulative CTV V100 were 88.0%, 98.4%, 99.2%, and 99.3% for the IGRT, ART, reoptimization, and original plans, respectively. The corresponding rectal V45Gy (V60Gy) were 58.7% (27.3%), 48.1% (20.7%), 43.8% (16.1%), and 44.9% (16.8%). The results for bladder were comparable among three schemes. Paired two-tailed Wilcoxon signed-rank tests were performed and it was found that ART and reoptimization provide better target coverage and better OAR sparing, especially rectum sparing. The interfractional organ motions and deformations during prostate-bed irradiation are significant. The online adaptive replanning scheme is capable of effectively addressing the large organ deformation, resulting in cumulative doses equivalent to those originally planned.
To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for pa... more To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT). Prostate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms. At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P <or= .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein. LTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.
Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate... more Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results. Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF). Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.
International Journal of Radiation Oncology*Biology*Physics, 1998
The purpose of this study was to assess response, toxicity, failure patterns, and survival differ... more The purpose of this study was to assess response, toxicity, failure patterns, and survival differences in three chemotherapy (ChT)/radiation therapy (RT) sequencing strategies for locally advanced non-small cell lung cancer (NSCLC). Five completed Radiation Therapy Oncology Group (RTOG) trials for Stage II-IIIA/B inoperable NSCLC patients employed one of the three following strategy groupings: 1) sequential ChT followed by standard RT (60 Gy in 6 weeks); 2) combined sequential and concurrent ChT and standard RT (60 Gy in 6 weeks); or 3) concurrent ChT and hyperfractionated RT (69.6 Gy in 6 weeks). All five trials required KPS > or = 70; two trials (314 patients) required <5% weight loss and three trials (147 patients) had no minimum weight loss requirement. In all five trials the ChT used cisplatin with either vinblastine or oral etoposide. Combining data for the five trials yielded an evaluable group of 461 patients. The three methods of sequencing ChT and RT were evaluated for differences in response, acute and late toxicity, patterns of failure, and survival. Acute toxicity was defined as that occurring within 90 days from the start of RT. Late toxicity was defined as that occurring after 90 days from the start of RT. Acute or late toxicity > or = grade 3 was defined as severe. Site of first failure was recorded by date. In-field failure excluded distant metastasis as a failure and included only tissue in the RT treatment field. Overall progression-free survival (PFS) was defined as survival without evidence of intra- or extrathoracic tumor or death from any cause. Group 1 had a lower overall response rate (63%) compared to either Group 2 (77%) or Group 3 (79%), p = 0.03 and 0.003, respectively. Overall grade 4/5 acute toxicities were nearly equal between groups. The severe nonhematologic acute toxicities were significantly different by strategy group (p < 0.0001). Group 1 and 2 were not statistically different. Group 3 had significantly more patients with severe acute nonhematologic toxicity (55%) than either Group 1 (27%) or 2 (34%) with p < 0.0001 and p = 0.0005, respectively. This was due to a severe acute esophagitis rate of 34% for Group 3 versus 1.3% for Group 1 and 6% for Group 2 (p < 0.0001 for both comparisons). Overall grade 4/5 late toxicities did not differ by group. Severe late nonhematologic toxicities were different by group (p = 0.0098). Group 1 patients had significantly fewer severe late nonhematologic toxicities (14%) compared to patients in Groups 2 (26%) or 3 (28%) (p = 0.046 and 0.038, respectively). Severe late lung toxicity was 10% for Group 1 compared to 21% and 20% for Groups 2 and 3, respectively. Severe late lung toxicities differed by group (p = 0.033), but not severe late esophagitis (p = 0.077). There were no differences between the three strategy groups for patterns of first failure. The in-field failures were higher in Group 2 (71%) compared to Groups 1 (56%) and 3 (55%), p = 0.0478. Pairwise comparisons yielded p-values of 0.068 and 0.015 for Group 2 versus 1 and Group 2 versus 3, respectively. Three-year PFS was better in Group 2 (15%) and 3 (15%) compared to Group 1 (7%), but not statistically significant (p = 0.454). Similarly, in-field PFS was better in Group 2 (17%) and 3 (20%) than Group 1 (9%), but not significant (p = 0.167). There were improvements in 3-year survival for Group 2 (17%) and Group 3 (25%) compared to Group 1 (15%), but the differences were not statistically significant (p = 0.47). The same results were present for patients with less than 5% weight loss and patients with stage IIIA tumors. Thus, concurrent ChT and hyperfractionated RT had a higher incidence of severe acute esophageal toxicity. Severe late lung toxicity with concurrent ChT/hyperfractionated RT, as well as with induction ChT followed by concurrent ChT/standard RT, may be greater compared to sequential ChT/RT. (ABSTRACT TRUNCATED)
International Journal of Radiation Oncology*Biology*Physics, 2006
To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity afte... more To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. All patients were treated with external beam radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity was graded according to the Common Toxicity Criteria Version 2.0, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used for all other toxicity. A total of 138 patients from 28 institutions were entered on this study. Acute toxicity information was available in 131 patients, and 127 patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed. The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5 toxicity has been observed. The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience.
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Papers by Colleen Lawton