Effects of irradiation doses <10 Gy and irradiated bone volume on the change in blood counts during and after pelvic irradiation

Laure Kuntz, Audrey Keller, Clara Le Fèvre, Inès Menoux, Gianandrea Pietta, Alicia Thiery, Catherine Schumacher, Manon Voegelin, Georges Noel


Background: Bone marrow is one of the organs at risk of complications during irradiation due to its radiosensitivity. Hematopoietic toxicity remains one of the main toxicities during irradiation of pelvis. Modern radiotherapy techniques, such as intensity modulation and three-dimensional conformal radiotherapy, allow for better dose compliance in target volumes while optimally sparing organs at risk. There is a lack of prospective studies and comparative trials specifying the dose constraints according to the presence or absence of chemotherapy and correlating with the patient’s bone marrow potential.

Methods: This monocentric and prospective study conducted by the Strasbourg Europe Cancerology Institute aims to evaluate the hematological toxicity in patients treated with pelvic irradiation for prostate, rectum, anal canal, endometrium, or cervix cancer. One hundred patients will be included. The primary objective is to quantify the relationship between acute hematological toxicity and delivered doses and irradiated volumes in pelvic bone marrow for pelvic cancers. The prescribed dose to the pelvis depends on the tumor location, from 25 Gy in 5 fractions for rectal cancer to 78 Gy in 39 fractions for low-risk prostate cancer. Hematological toxicity will be measured by weekly blood count during radiotherapy and at one month and three months after the end of radiotherapy.

Conclusions: The aim of this study is to improve and optimize radiotherapy if a dose limit or volume constraint is imposed by the results of the study. To our knowledge, this is the first study including several types of pelvic cancers and involving patients treated exclusively with radiotherapy, chemoradiotherapy or radiohormonotherapy.

Trial Registration: Trial registration number is NCT04626466.


Bone marrow, Hematologic toxicity, Pelvic irradiation, Radiotherapy, IMRT

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Antoni D, Natarajan-Ame S, Meyer P, Niederst C, Bourahla K, Noel G. Contribution of three-dimensional conformal intensity-modulated radiation therapy for women affected by bulky stage II supradiaphragmatic Hodgkin disease. Radiat Oncol. 2013;8:112.

Klopp AH, Moughan J, Portelance L, Miller BE, Salehpour MR, Hildebrandt E, et al. Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer. Int J Radiat Oncol Biol Phys. 2013;86:83-90.

Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;52:1330-7.

Parker RG, Berry HC. Late effects of therapeutic irradiation on the skeleton and bone marrow. Cancer. 1976;37:1162-71.

Dainiak N. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002;30:513-28.

Erpolat OP, Alco G, Caglar HB, Igdem S, Saran A, Dagoglu N, et al. Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study. Eur J Gynaecol Oncol. 2014;35:62-6.

Chang Y, Yang Z-Y, Li G-L, Li Q, Yang Q, Fan J-Q, et al. Correlations Between Radiation Dose in Bone Marrow and Hematological Toxicity in Patients With Cervical Cancer: A Comparison of 3DCRT, IMRT, and RapidARC. Int J Gynecol Cancer. 2016;26:770-6.

Cozzarini C, Noris Chiorda B, Sini C, Fiorino C, Briganti A, Montorsi F, et al. Hematologic Toxicity in Patients Treated With Postprostatectomy Whole-Pelvis Irradiation With Different Intensity Modulated Radiation Therapy Techniques Is Not Negligible and Is Prolonged: Preliminary Results of a Longitudinal, Observational Study. Int J Rad Oncol Biol Phys. 2016;95:690-5.

Noël G, Antoni D, Barillot I, Chauvet B. Delineation of organs at risk and dose constraints. Cancer Radiother. 2016;20:36-60.

Kuntz L, Noel G. Pelvic irradiation and hematopoietic toxicity: A review of the literature. Cancer Radiother. 2021;25:77-91.

de Crevoisier R, Pommier P, Latorzeff I, Chapet O, Chauvet B, Hennequin C. Prostate cancer external beam radiotherapy. Cancer Radiother. 2016;20:200-9.

Peiffert D, Créhange G, Vendrely V, Baumann A-S, Faivre J-C, Huger S. Radiotherapy for anal canal cancers. Cancer Radiother. 2016;20:183-8.

Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23:1-34.

Barillot I, Haie-Méder C, Charra Brunaud C, Peignaux K, Kerr C, Thomas L. Radiotherapy of cervix and endometrial carcinoma. Cancer Radiother. 2016;20:189-95.

Bourdais R, Achkar S, Chauffert-Yvart L, Pasquier D, Sargos P, Blanchard P, et al. Prophylactic nodal radiotherapy in prostate cancer. Cancer Radiother. 2019;23:688-95.

Ballester M, Bendifallah S, Daraï E. European guidelines (ESMO-ESGO-ESTRO consensus conference) for the management of endometrial cancer. Bull Cancer. 2017;104:1032-8.

Dhermain F, Reyns N, Colin P, Métellus P, Mornex F, Noël G. Stereotactic radiotherapy in brain metastases. Cancer Radiother. 2015;19:25-9.

Peiffert D, Créhange G, Vendrely V, Baumann A-S, Faivre J-C, Huger S, et al. Radiotherapy of rectal carcinoma. Cancer Radiother. 2016;20:179-82.

Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:22-40.

Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, Peiffert D, Cervantes A, et al. Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2014;40:1165-76.

Loubersac T, Guimas V, Rio E, Libois V, Rigaud J, Supiot S. Oligorecurrent prostate cancer: current management and perspectives. Bull Cancer. 2020;107:35-40.

Vaugier L, Palpacuer C, Rio E, Goineau A, Pasquier D, Buthaud X, et al. Early Toxicity of a Phase 2 Trial of Combined Salvage Radiation Therapy and Hormone Therapy in Oligometastatic Pelvic Node Relapses of Prostate Cancer (OLIGOPELVIS GETUG P07). Int J Radiat Oncol Biol Phys. 2019;103:1061-7.

Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019;19:816.

Mahantshetty U, Krishnatry R, Chaudhari S, Kanaujia A, Engineer R, Chopra S, et al. Comparison of 2 contouring methods of bone marrow on CT and correlation with hematological toxicities in non-bone marrow-sparing pelvic intensity-modulated radiotherapy with concurrent cisplatin for cervical cancer. Int J Gynecol Cancer. 2012;22:1427-34.

Franco P, Ragona R, Arcadipane F, Mistrangelo M, Cassoni P, Rondi N, et al. Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer. Clin Transl Oncol. 2017;19:67-75.

Albuquerque K, Giangreco D, Morrison C, Siddiqui M, Sinacore J, Potkul R, et al. Radiation-related predictors of hematologic toxicity after concurrent chemoradiation for cervical cancer and implications for bone marrow-sparing pelvic IMRT. Int J Radiat Oncol Biol Phys. 2011;79:1043-7.

Bao Z, Wang D, Chen S, Chen M, Jiang D, Yang C, et al. Optimal dose limitation strategy for bone marrow sparing in intensity-modulated radiotherapy of cervical cancer. Radiat Oncol. 2019;14:118.

Sini C, Fiorino C, Perna L, Noris Chiorda B, Deantoni CL, Bianchi M, et al. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation. Radiother Oncol. 2016;118:79-84.

Mell LK, Sirák I, Wei L, Tarnawski R, Mahantshetty U, Yashar CM, et al. Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2). Int J Radiat Oncol Biol Phys. 2017;97:536-45.

Rattan R, Kapoor R, Bahl A, Gupta R, Oinam AS, Kaur S. Comparison of bone marrow sparing intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in carcinoma of anal canal: a prospective study. Ann Transl Med. 2016;4:70.

Freese C, Sudhoff M, Lewis L, Lamba M, Kharofa J. The volume of PET-defined, active bone marrow spared predicts acute hematologic toxicities in anal cancer patients receiving concurrent chemoradiotherapy. Acta Oncologica. 2018;57:683-6.

Rose BS, Liang Y, Lau SK, Jensen LG, Yashar CM, Hoh CK, et al. Correlation between radiation dose to 18F-FDG-PET defined active bone marrow subregions and acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2012;83:1185-91.

Jianyang W, Yuan T, Yuan T, Xin W, Ning L, Hua R, et al. A prospective phase II study of magnetic resonance imaging guided hematopoietical bone marrow-sparing intensity-modulated radiotherapy with concurrent chemotherapy for rectal cancer. Radiol Med. 2016;121:308-14.

Wan J, Liu K, Li K, Li G, Zhang Z. Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy? Radiat Oncol. 2015;10:162.

Franco P, Arcadipane F, Ragona R, Lesca A, Gallio E, Mistrangelo M, et al. Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation. Cancer Invest. 2018;36:279-88.

Zhang C, Dong J, Shen T, Li Y, Yang Z, Cheng X, et al. Comparison of the application among intensity-modulated radiotherapy, 3D-conformal radiotherapy and conventional radiotherapy for locally advanced middle-low rectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi. 2018;21:1414-20.

Du XX, Yang H, Zhang HJ, Li LA, Fan WS, Meng YG. Clinical study of intensity modulated radiotherapy and three-dimensional conformal radiotherapy with three-dimensional brachytherapy and concurrent chemotherapy for patients with advanced cervical cancer. Zhonghua Fu Chan Ke Za Zhi. 2017;52:679-86.

Avinash HU, Arul Ponni TR, Janaki MG, Kirthi Koushik AS, Kumar SM. A prospective dosimetric and clinical comparison of acute hematological toxicities in three-dimensional conformal radiation therapy and intensity modulated radiation therapy with concurrent chemotherapy in carcinoma cervix. J Cancer Res Ther. 2015;11:83-7.

Ni J, Yin ZM, Yuan SH, Liu NF, Li L, Xu XX, et al. A randomized study of intensity-modulated radiation therapy versus three dimensional conformal radiation therapy for pelvic radiation in patients of post-operative treatment with gynecologic malignant tumor. Zhonghua Fu Chan Ke Za Zhi. 2017;52:168-74.

Naik A, Gurjar OP, Gupta KL, Singh K, Nag P, Bhandari V. Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study. Cancer/Radiothérapie. 2016;20:370-6.

Julie DAR, Oh JH, Apte AP, Deasy JO, Tom A, Wu AJ, et al. Predictors of acute toxicities during definitive chemoradiation using intensity-modulated radiotherapy for anal squamous cell carcinoma. Acta Oncol. 2016;55:208-16.

Aptel F, Cucherat M, Blumen-Ohana E, Denis P. Critical reading of clinical trials. J Fr Ophtalmol. 2011;34:755-61.