Correlation Between Radiation Dose to 18F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated with Chemoradiotherapy

Rose, Brent S.; Liang, Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

doi:10.1016/j.ijrobp.2011.09.048

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Correlation Between Radiation Dose to ¹⁸F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated with Chemoradiotherapy

Brent S. Rose, M.D.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
Yun Liang, Ph.D.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
Steven K. Lau, Ph.D.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
Lindsay G. Jensen, B.A.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
Catheryn M. Yashar, M.D.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
Carl K. Hoh, M.D.
- Division of Nuclear Medicine, University of California, San Diego, La Jolla, CA
Loren K. Mell, M.D.
- Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA
- Reprint requests to: Loren K. Mell, M.D., Department of Radiation Oncology, UCSD Moores Cancer center, 3855 Health Sciences Dr. #0843, La Jolla, CA 92093-0843. Tel: (858) 822-6040; Fax: (858) 822-5568

Received 27 April 2011; received in revised form 4 August 2011; accepted 21 September 2011. published online 23 January 2012.
Corrected Proof

Purpose

To test the hypothesis that radiation dose to ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET)-defined active bone marrow (BM_ACT) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.

Methods and Materials

The conditions of 26 women with cervical cancer who underwent ¹⁸F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM_ACT was defined as the subregion of total bone marrow (BM_TOT) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM_INACT) was defined as BM_TOT − BM_ACT. Generalized linear modeling was used to test the correlation between BM_ACT and BM_INACT dose–volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC).

Results

Increased BM_ACT mean dose was significantly associated with decreased log(WBC) nadir (β = −0.04; 95% CI, −0.07to −0.01; p = 0.009), decreased log(ANC) nadir (β = −0.05; 95% CI, −0.08 to −0.02; p = 0.006), decreased hemoglobin nadir (β = −0.16; 95% CI, −0.27 to −0.05; p = 0.010), and decreased platelet nadir (β = −6.16; 95% CI, −9.37 to −2.96; p < 0.001). By contrast, there was no association between BM_INACT mean dose and log(WBC) nadir (β = −0.01; 95% CI, −0.06 to 0.05; p = 0.84), log(ANC) nadir (β = −0.03; 95% CI, −0.10 to 0.04; p = 0.40), hemoglobin nadir (β = −0.09; 95% CI, −0.31 to 0.14; p = 0.452), or platelet nadir (β = −3.47; 95% CI, −10.44 to 3.50; p = 0.339).

Conclusions

Irradiation of BM subregions with higher ¹⁸F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM_ACT subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM_ACT.

Keywords: Cervical cancer, Hematologic toxicity, Bone marrow, ¹⁸F-fluorodeoxyglucose positron emission tomography