Radiation-Related Predictors of Hematologic Toxicity After Concurrent Chemoradiation for Cervical Cancer and Implications for Bone Marrow–Sparing Pelvic IMRT

Albuquerque, Kevin; Giangreco, David; Morrison, Courtney; Siddiqui, Mohammed; Sinacore, James; Potkul, Ronald K.; Roeske, John C.

doi:10.1016/j.ijrobp.2009.12.025

Cited by 134 publications

(121 citation statements)

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“…However, toxicity rates are not negligible and severe reactions can be observed to gastrointestinal tract, genitalia and skin, especially whenever nonconformal techniques are employed [3]. In this setting, hematologic toxicity (HT) may limit and decrease treatment intensity, with patients potentially experiencing unplanned treatment breaks with a consequent increased in overall treatment time or infections, bleeding or asthenia [4]. Even if intensity-modulated radiotherapy (IMRT) is employed, major HT rates may be up to 60 % [5,6].…”

Section: Introductionmentioning

confidence: 99%

Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients

et al. 2016

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To test the hypothesis that irradiated volume of specific subregions of pelvic active bone marrow as detected by (18)FDG-PET may be a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation, we analyzed 44 patients submitted to IMRT and concurrent chemotherapy. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. Active BM was characterized employing (18)FDG-PET and characterized in all subregions as the volume having standard uptake values (SUVs) higher than SUVmean. All other regions were defined as inactive BM. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Generalized linear modeling was used to find correlations between dosimetric variables and blood cells nadirs. WBC nadir was significantly correlated with LSBM mean dose (β = -1.852; 95 % CI -3.205/-0.500; p = 0.009), V10 (β = -2.153; 95 % CI -4.263/-0.721; p = 0.002), V20 (β = -2.081; 95 % CI -4.880/-0.112; p = 0.003), V30 (β = -1.971; 95 % CI -4.748/-0.090; p = 0.023) and IBM V10 (β = -0.073; 95 % CI -0.106/-0.023; p = 0.016). ANC nadir found to be significantly associated with LSBM V10 (β = -1.878; 95 % CI -4.799/-0.643; p = 0.025), V20 (β = -1.765; 95 % CI -4.050/-0.613; p = 0.030) and IBM V10 (β = -0.039; 95 % CI -0.066/-0.010; p = 0.027). Borderline significance was found for correlation between Plt nadir and LSBM V30 (β = -0.056; 95 % CI -2.748/-0.187; p = 0.060), V40 (β = -0.059; 95 % CI -3.112/-0.150; p = 0.060) and IBM V30 (β = -0.028; 95 % CI -0.074/-0.023; p = 0.056). No inactive BM subsites were found to be correlated with any blood cell nadir. (18)FDG-PET is able to define active bone marrow within pelvic osseous structures. LSBM is the strongest predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation.

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Section: Introductionmentioning

confidence: 99%

Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients

et al. 2016

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“…Prior studies indicate that reducing dose to ABM is likely to be an effective method to reduce HT, potentially allowing the delivery of more chemotherapy [9,10,15,23,24]. Normal tissue complication studies have found that decreased dose to the pelvic bone marrow is associated with reduced HT [9,10,23].…”

Section: Discussionmentioning

confidence: 99%

“…Normal tissue complication studies have found that decreased dose to the pelvic bone marrow is associated with reduced HT [9,10,23]. Furthermore, pelvic bone marrow dose-volume metrics have been linked to weekly reductions in peripheral blood counts in cervical cancer patients receiving CRT [25].…”

Section: Discussionmentioning

confidence: 99%

Feasibility of atlas-based active bone marrow sparing intensity modulated radiation therapy for cervical cancer

Noticewala

Williamson

et al. 2017

Radiotherapy and Oncology

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F-FDG PET/CT Atlas-based Active bone marrow Radiotherapy planning a b s t r a c tBackground: To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity modulated radiation therapy (IMRT) yields similar dosimetric results compared to custom ABM-sparing IMRT for cervical cancer patients. Methods: We sampled 62 cervical cancer patients with pre-treatment FDG-PET/CT in training (n = 32) or test (n = 30) sets. ABM was defined as the subvolume of the pelvic bone marrow (PBM) with standardized uptake value (SUV) above the mean on the average FDG-PET image (ABM Atlas ) vs. the individual's PET (ABM Custom ). Both were deformed to the planning CT. Overlap between the two subvolumes was measured using the Dice coefficient. Three IMRT plans designed to spare PBM, ABM Atlas , or ABM Custom were compared for 30 test patients. Dosimetric parameters were used to evaluate plan quality. Results: ABM Atlas and ABM Custom volumes were not significantly different (p = 0.90), with a mean Dice coefficient of 0.75, indicating good agreement. Compared to IMRT plans designed to spare PBM and ABM Custom , ABM Atlas -sparing IMRT plans achieved excellent target coverage and normal tissue sparing, without reducing dose to ABM Custom (mean ABM Custom dose 29.4 Gy vs. 27.1 Gy vs. 26.9 Gy, respectively; p = 0.10); however, PTV coverage and bowel sparing were slightly reduced. Conclusions: Atlas-based ABM sparing IMRT is clinically feasible and may obviate the need for customized ABM-sparing as a strategy to reduce hematologic toxicity.Ó 2017 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 123 (2017) 325-330Concurrent chemoradiotherapy (CRT) is standard treatment for women with locoregionally advanced cervical cancer [1][2][3][4][5]. However, hematologic toxicity (HT) is a significant clinical problem that limits the intensity of CRT, which can lead to chemotherapy dose reductions and/or treatment breaks, potentially compromising patient outcomes [6][7][8]. Clinical studies have shown that increased radiation dose and volume of irradiated pelvic bone marrow (PBM) are associated with increased risk of HT, suggesting that techniques designed to limit PBM irradiation could reduce toxicity [9,10]. Intensity modulated radiation therapy (IMRT) is a technology that can reduce toxicity by decreasing dose to normal tissues, without compromising tumor control. However, current IMRT plans are constrained by the large PBM volume to avoid, as defined by computed tomography (CT) [11,12].Previous studies have suggested that refining IMRT plans to spare hematopoietically ''active" bone marrow (ABM) subregions could be an effective strategy to reduce HT [13][14][15][16][17][18]. Functional imaging using [ Although studies have found that incorporating functional imaging with IMRT planning is likely to be effective [15][16][17][18][19], this approach remains investigational. Moreover, functional imaging is expensive and not universally available.To address this problem, McGuire et al. [20] proposed a method to identify ABM ...

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“…Leukopenia and neutropenia can put patients at increased risk for infection and hospitalization, which can compromise treatment efficacy by prolonging the overall treatment time. Multiple institutions have demonstrated that the volume of bone marrow receiving a low dose of radiation, V10 and V20, strongly correlates with cytopenias [8,9,15,16]. In our study, we found that the mean absolute volume of bone marrow spared 10 Gy was significantly higher with IMPT plans, 814 cm 3 compared with VMAT plans, 111 cm 3 (P , .0001); and the volume of bone marrow spared 20 Gy was also significantly higher (932 cm 3 versus 246 cm 3 , P , .0001).…”

Section: Discussionmentioning

confidence: 99%

Dosimetric Comparison of Intensity-Modulated Proton Therapy and Volumetric-Modulated Arc Therapy in Anal Cancer Patients and the Ability to Spare Bone Marrow

Meier

Mascia

Wolf

et al. 2017

International Journal of Particle Therapy

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Radiation-Related Predictors of Hematologic Toxicity After Concurrent Chemoradiation for Cervical Cancer and Implications for Bone Marrow–Sparing Pelvic IMRT

Cited by 134 publications

References 18 publications

Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients

Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients

Feasibility of atlas-based active bone marrow sparing intensity modulated radiation therapy for cervical cancer

Dosimetric Comparison of Intensity-Modulated Proton Therapy and Volumetric-Modulated Arc Therapy in Anal Cancer Patients and the Ability to Spare Bone Marrow

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