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Title: Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies

Abstract

Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). Methods and Materials: We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed {sup 18}F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. Results: In gynecologic cancer patients, the mean functional BM V{sub 10} (volume receiving {>=}10 Gy) and V{sub 20} (volume receivingmore » {>=}20 Gy) were 85% vs 94% (P<.0001) and 70% vs 82% (P<.0001), respectively, for functional BM-sparing IMRT vs total BM-sparing IMRT. In anal cancer patients, the corresponding values were 75% vs 77% (P=.06) and 62% vs 67% (P=.002), respectively. Of 10 subjects treated with functional BM-sparing pelvic IMRT, 3 (30%) had acute grade 3 hematologic toxicity or greater. Conclusions: IMRT can reduce dose to BM subregions identified by {sup 18}F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial.« less

Authors:
 [1];  [2];  [3]; ;  [1];  [2];  [1];  [3];  [1];  [2];  [1];  [4];  [5];  [1];  [2];  [3];
  1. Department of Radiation Oncology, University of California, San Diego, La Jolla, California (United States)
  2. (United States)
  3. Department of Radiology, University of California, San Diego, La Jolla, California (United States)
  4. Department of Gynecologic Oncology, University of California, San Diego, La Jolla, California (United States)
  5. Division of Hematology-Oncology, University of California, San Diego, La Jolla, California (United States)
Publication Date:
OSTI Identifier:
22149766
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 85; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BONE MARROW; CHEMOTHERAPY; FLUORINE 18; FLUORODEOXYGLUCOSE; HYPOTHESIS; MEN; NEOPLASMS; NMR IMAGING; PATIENTS; PELVIS; PLANNING; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; RADIOTHERAPY; REVIEWS; SIMULATION; TOXICITY; VERTEBRAE

Citation Formats

Liang Yun, Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Mark, Yashar, Catheryn M., Rose, Brent S., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Cornell, Mariel, Hoh, Carl K., Lawson, Joshua D., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Einck, John, Saenz, Cheryl, Fanta, Paul, Mundt, Arno J., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Graeme M., and and others. Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies. United States: N. p., 2013. Web. doi:10.1016/J.IJROBP.2012.04.044.
Liang Yun, Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Mark, Yashar, Catheryn M., Rose, Brent S., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Cornell, Mariel, Hoh, Carl K., Lawson, Joshua D., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Einck, John, Saenz, Cheryl, Fanta, Paul, Mundt, Arno J., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Graeme M., & and others. Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies. United States. doi:10.1016/J.IJROBP.2012.04.044.
Liang Yun, Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Mark, Yashar, Catheryn M., Rose, Brent S., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Cornell, Mariel, Hoh, Carl K., Lawson, Joshua D., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Einck, John, Saenz, Cheryl, Fanta, Paul, Mundt, Arno J., Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California, Bydder, Graeme M., and and others. 2013. "Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies". United States. doi:10.1016/J.IJROBP.2012.04.044.
@article{osti_22149766,
title = {Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies},
author = {Liang Yun and Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California and Bydder, Mark and Yashar, Catheryn M. and Rose, Brent S. and Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California and Cornell, Mariel and Hoh, Carl K. and Lawson, Joshua D. and Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California and Einck, John and Saenz, Cheryl and Fanta, Paul and Mundt, Arno J. and Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, California and Bydder, Graeme M. and and others},
abstractNote = {Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). Methods and Materials: We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed {sup 18}F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. Results: In gynecologic cancer patients, the mean functional BM V{sub 10} (volume receiving {>=}10 Gy) and V{sub 20} (volume receiving {>=}20 Gy) were 85% vs 94% (P<.0001) and 70% vs 82% (P<.0001), respectively, for functional BM-sparing IMRT vs total BM-sparing IMRT. In anal cancer patients, the corresponding values were 75% vs 77% (P=.06) and 62% vs 67% (P=.002), respectively. Of 10 subjects treated with functional BM-sparing pelvic IMRT, 3 (30%) had acute grade 3 hematologic toxicity or greater. Conclusions: IMRT can reduce dose to BM subregions identified by {sup 18}F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial.},
doi = {10.1016/J.IJROBP.2012.04.044},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 85,
place = {United States},
year = 2013,
month = 2
}
  • Purpose: To determine factors predictive for hematologic toxicity (HT) associated with concurrent chemoradiation for Stage II through IV cervical cancer. Methods and Materials: The medical records of 40 women receiving concurrent chemoradiation for cervical cancer were reviewed. Hematologic toxicity was defined by use of Common Terminology Criteria for Adverse Events (version 3.0). Variables predicting for HT including age, body mass index, transfusions, and bone marrow volumes irradiated were included in the data analysis. Results: Of the patients, 13 (32.5%) had Grade 0 or 1 HT and 27 (67.5%) had Grade 2 through 4 HT (HT2+). Multiple logistic regression analysis ofmore » potential predictors showed that only the volume of bone receiving 20 Gy (V20) for whole pelvic bone tended toward significance for predicting HT2+. A strong correlation was noted between HT2+ and V20 (r = 0.8, p < 0.0001). A partitioning analysis to predict HT2+ showed a cutoff value of 79.42% (approximately 80%) for V20 of whole pelvic bone. That is, if the V20 of the whole pelvis exceeds 80%, the risk of HT2+ developing increases by a factor (odds ratio) of 4.5 (95%, confidence interval, 1.08-18.69) (p < 0.05). Conclusions: We have shown a correlation between bone marrow volume radiated and development of HT. This has implications for use of pelvic intensity-modulated radiation therapy, which can potentially decrease the volume of bone marrow radiated.« less
  • Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was gradedmore » according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). Conclusion: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.« less
  • Purpose: To describe voice and speech quality changes and their predictors in patients with locally advanced oropharyngeal cancer treated on prospective clinical studies of organ-preserving chemotherapy–intensity modulated radiation therapy (chemo-IMRT). Methods and Materials: Ninety-one patients with stage III/IV oropharyngeal cancer were treated on 2 consecutive prospective studies of definitive chemoradiation using whole-field IMRT from 2003 to 2011. Patient-reported voice and speech quality were longitudinally assessed from before treatment through 24 months using the Communication Domain of the Head and Neck Quality of Life (HNQOL-C) instrument and the Speech question of the University of Washington Quality of Life (UWQOL-S) instrument, respectively.more » Factors associated with patient-reported voice quality worsening from baseline and speech impairment were assessed. Results: Voice quality decreased maximally at 1 month, with 68% and 41% of patients reporting worse HNQOL-C and UWQOL-S scores compared with before treatment, and improved thereafter, recovering to baseline by 12-18 months on average. In contrast, observer-rated larynx toxicity was rare (7% at 3 months; 5% at 6 months). Among patients with mean glottic larynx (GL) dose ≤20 Gy, >20-30 Gy, >30-40 Gy, >40-50 Gy, and >50 Gy, 10%, 32%, 25%, 30%, and 63%, respectively, reported worse voice quality at 12 months compared with before treatment (P=.011). Results for speech impairment were similar. Glottic larynx dose, N stage, neck dissection, oral cavity dose, and time since chemo-IMRT were univariately associated with either voice worsening or speech impairment. On multivariate analysis, mean GL dose remained independently predictive for both voice quality worsening (8.1%/Gy) and speech impairment (4.3%/Gy). Conclusions: Voice quality worsening and speech impairment after chemo-IMRT for locally advanced oropharyngeal cancer were frequently reported by patients, underrecognized by clinicians, and independently associated with GL dose. These findings support reducing mean GL dose to as low as reasonably achievable, aiming at ≤20 Gy when the larynx is not a target.« less
  • Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less
  • Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V{sub 10} and PBM-V{sub 20}) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximalmore » femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V{sub 5}, V{sub 10}, V{sub 15}, and V{sub 20} were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V{sub 10}, V{sub 15}, and V{sub 20} (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.« less