Skip to main content
Top
Published in: Radiation Oncology 1/2020

Open Access 01-12-2020 | Cervical Cancer | Research

Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial

Authors: Jin Huang, Fei Gu, Tianlong Ji, Jing Zhao, Guang Li

Published in: Radiation Oncology | Issue 1/2020

Login to get access

Abstract

Purpose

To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing grade 2 or higher hematological toxicity (HT2+) for patients with cervical cancer treated with concurrent chemoradiotherapy.

Methods and materials

A total of 164 patients with Stage Ib2–IIIb cervical cancer were prospectively enrolled from March 2018 to March 2019 at a single center and were randomly allocated into the PBMS group or the control group. The control group received weekly cisplatin concurrently with IMRT, followed by intracavitary brachytherapy. The PBMS group additionally received PBM dose constraint. The dosimetric parameters of the pelvic bone (PB) and the subsites including hip bone (HIP) and lumbosacral spine (LSS) and the corresponding bone marrow were recorded. The endpoint of the trial was acute hematologic or gastrointestinal toxicity. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.

Results

Eighty-two patients in the PBMS group and 82 in the control group were enrolled for statistical analysis. The incidence of HT2+ in the PBMS group was 50.0%, significantly lower than the 69.5% incidence in the control group (P = 0.02). Patients with PB V40 ≥ 28% were more likely to experience HT2+ (OR = 2.85, P = 0.006), while the incidence of grade 2 or higher gastrointestinal toxicity (GT2+) events did not differ significantly between the two groups (P > 0.05). Dosimetric parameters of LSS showed stronger associations with HT2+ than other subsites. The patients with LSS V10 ≥ 87% and LSS mean ≥ 39 Gy were more likely to experience HT2+ (OR = 3.13, P = 0.001;OR = 3.03, P = 0.002, respectively).

Conclusion

PBMS-IMRT reduced HT compared with IMRT alone. Efforts to maintain LSS V10 < 87%, LSS mean < 39 Gy and PB V40 < 28% simultaneously may reduce the risk of HT2 +.

Trial registration

The trial was registered with Chinese clinical trial registry (ChiCTR1800015069​).
Appendix
Available only for authorised users
Literature
1.
go back to reference Thomas GM. Improved treatment for cervical Cancer - concurrent chemotherapy and radiotherapy. N Engl J Med. 1999;340(15):1198–200.PubMedCrossRef Thomas GM. Improved treatment for cervical Cancer - concurrent chemotherapy and radiotherapy. N Engl J Med. 1999;340(15):1198–200.PubMedCrossRef
2.
go back to reference Peters WA, Liu PY, Barrett RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18:1606–13.PubMedCrossRef Peters WA, Liu PY, Barrett RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18:1606–13.PubMedCrossRef
3.
go back to reference Torres MA, Jhingran A, Thames HD, et al. Comparison of treatment tolerance and outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy in a prospective randomized trial or with standard treatment. Int J Radiat Oncol Biol Phys. 2008;70:118–25.PubMedCrossRef Torres MA, Jhingran A, Thames HD, et al. Comparison of treatment tolerance and outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy in a prospective randomized trial or with standard treatment. Int J Radiat Oncol Biol Phys. 2008;70:118–25.PubMedCrossRef
4.
go back to reference Green JA, Kirwan JM, Tierney JF, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix. Lancet. 2001;358:781–6.PubMedCrossRef Green JA, Kirwan JM, Tierney JF, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix. Lancet. 2001;358:781–6.PubMedCrossRef
5.
go back to reference Kirwan JM, Symonds P, Green JA, et al. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radiother Oncol. 2003;68:217–26.PubMedCrossRef Kirwan JM, Symonds P, Green JA, et al. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radiother Oncol. 2003;68:217–26.PubMedCrossRef
6.
go back to reference Abu-Rustum NR, Lee S, Correa A, et al. Compliance with and acute hematologic toxic effects of chemoradiation in indigent women with cervical cancer. Gynecol Oncol. 2001;81:88–91.PubMedCrossRef Abu-Rustum NR, Lee S, Correa A, et al. Compliance with and acute hematologic toxic effects of chemoradiation in indigent women with cervical cancer. Gynecol Oncol. 2001;81:88–91.PubMedCrossRef
7.
go back to reference Mahantshetty U, Krishnatry R, Chaudhari 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(8):1427–34.PubMedCrossRef Mahantshetty U, Krishnatry R, Chaudhari 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(8):1427–34.PubMedCrossRef
8.
go back to reference Kurotaki D, Uede T, Tamura T. Functions and development of red pulp macrophages. Microbiol Immunol. 2015;59(2):55–62.PubMedCrossRef Kurotaki D, Uede T, Tamura T. Functions and development of red pulp macrophages. Microbiol Immunol. 2015;59(2):55–62.PubMedCrossRef
9.
go back to reference Omatsu Y. The niche for hematopoietic stem and progenitor cells in bone marrow. Clin Calcium. 2016;26(5):671–6.PubMed Omatsu Y. The niche for hematopoietic stem and progenitor cells in bone marrow. Clin Calcium. 2016;26(5):671–6.PubMed
10.
go back to reference Cruet-Hennequart S, Drougard C, Shaw G, et al. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stemcells. PLoS One. 2015;10(3):e0119334.PubMedPubMedCentralCrossRef Cruet-Hennequart S, Drougard C, Shaw G, et al. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stemcells. PLoS One. 2015;10(3):e0119334.PubMedPubMedCentralCrossRef
11.
go back to reference Mauch P, Constine L, Greenberger J, et al. Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys. 1995;31:1319–39.PubMedCrossRef Mauch P, Constine L, Greenberger J, et al. Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys. 1995;31:1319–39.PubMedCrossRef
12.
go back to reference Damek-Poprawa M, Stefanik D, Levin LM, et al. Human bone marrow stromal cells display variable anatomic site-dependent response and recovery from irradiation. Arch Oral Biol. 2011;55(5):358–64.CrossRef Damek-Poprawa M, Stefanik D, Levin LM, et al. Human bone marrow stromal cells display variable anatomic site-dependent response and recovery from irradiation. Arch Oral Biol. 2011;55(5):358–64.CrossRef
13.
go back to reference Kleinerman RA, Littlefield LG, Tarone RE, et al. Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrowin patients treated for cancer of the cervix. Radiat Res. 1989;119(1):176–90.PubMedCrossRef Kleinerman RA, Littlefield LG, Tarone RE, et al. Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrowin patients treated for cancer of the cervix. Radiat Res. 1989;119(1):176–90.PubMedCrossRef
14.
go back to reference Noticewala SS, Li N, Williamson CW, et al. Longitudinal changes in active bone marrow for cervical Cancer patients treated with concurrent Chemoradiation Therapy. Int J Radiat Oncol Biol Phys. 2017;97(4):797–805.PubMedCrossRef Noticewala SS, Li N, Williamson CW, et al. Longitudinal changes in active bone marrow for cervical Cancer patients treated with concurrent Chemoradiation Therapy. Int J Radiat Oncol Biol Phys. 2017;97(4):797–805.PubMedCrossRef
15.
go back to reference Mell LK, Kochanski JD, Roeske JC, et al. Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol Biol Phys. 2006;66(5):1356–65.PubMedCrossRef Mell LK, Kochanski JD, Roeske JC, et al. Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol Biol Phys. 2006;66(5):1356–65.PubMedCrossRef
16.
go back to reference Albuquerque K, Giangreco D, Morrison C, 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(4):1043–7.PubMedCrossRef Albuquerque K, Giangreco D, Morrison C, 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(4):1043–7.PubMedCrossRef
17.
go back to reference Rose BS, Aydogan B, Liang Y, et al. Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patient streated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(3):800–7.PubMedCrossRef Rose BS, Aydogan B, Liang Y, et al. Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patient streated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(3):800–7.PubMedCrossRef
18.
go back to reference Klopp AH, Moughan J, Portelance, 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(1):83–90.PubMedPubMedCentralCrossRef Klopp AH, Moughan J, Portelance, 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(1):83–90.PubMedPubMedCentralCrossRef
19.
go back to reference Jianyang W, Yuan T, Yuan T, et al. A prospective phase II study of magnetic resonance imaging guided hematopoietical bone marrow-sparingintensity-modulated radiotherapy with concurrent chemotherapy for rectal cancer. Radiol Med. 2016;121(4):308–14.PubMedCrossRef Jianyang W, Yuan T, Yuan T, et al. A prospective phase II study of magnetic resonance imaging guided hematopoietical bone marrow-sparingintensity-modulated radiotherapy with concurrent chemotherapy for rectal cancer. Radiol Med. 2016;121(4):308–14.PubMedCrossRef
20.
go back to reference Bazan JG, Luxton G, Mok EC. Normal tissue complication probability modeling of acute hematologic toxicity in patients treated within tensity-modulated radiation therapy for squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2012;84(3):700–6.PubMedCrossRef Bazan JG, Luxton G, Mok EC. Normal tissue complication probability modeling of acute hematologic toxicity in patients treated within tensity-modulated radiation therapy for squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2012;84(3):700–6.PubMedCrossRef
21.
go back to reference Wan J, Liu K, Li K, et al. Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy? Radiat Oncol. 2015;10:162.PubMedPubMedCentralCrossRef Wan J, Liu K, Li K, et al. Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy? Radiat Oncol. 2015;10:162.PubMedPubMedCentralCrossRef
22.
go back to reference Sini C, Fiorino C, Perna L, et al. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancerradiotherapy with pelvic node irradiation. Radiother Oncol. 2016;118(1):79–84.PubMedCrossRef Sini C, Fiorino C, Perna L, et al. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancerradiotherapy with pelvic node irradiation. Radiother Oncol. 2016;118(1):79–84.PubMedCrossRef
23.
go back to reference Gandhi AK, Sharma DN, Rath GK, et al. Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3):542–8.PubMedCrossRef Gandhi AK, Sharma DN, Rath GK, et al. Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3):542–8.PubMedCrossRef
24.
go back to reference Simpson DR, Song WY, Moiseenko V, et al. Normal tissue complication probability analysis of acute gastrointestinal toxicity in cervical cancer patients undergoing IMRT. Int J Radiat Oncol Biol Phys. 2012;83:e81–6.PubMedCrossRef Simpson DR, Song WY, Moiseenko V, et al. Normal tissue complication probability analysis of acute gastrointestinal toxicity in cervical cancer patients undergoing IMRT. Int J Radiat Oncol Biol Phys. 2012;83:e81–6.PubMedCrossRef
25.
go back to reference Mundt AJ, Lujan AE, Rotmensch J, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;52:1330–7.PubMedCrossRef Mundt AJ, Lujan AE, Rotmensch J, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;52:1330–7.PubMedCrossRef
26.
go back to reference Mell LK, Sirák I, Wei L, 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(3):536.PubMedCrossRef Mell LK, Sirák I, Wei L, 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(3):536.PubMedCrossRef
27.
go back to reference Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the eastern cooperative Oncology group. Am J Clin Oncol. 1982;5(6):649–55.PubMedCrossRef Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the eastern cooperative Oncology group. Am J Clin Oncol. 1982;5(6):649–55.PubMedCrossRef
28.
go back to reference Dimopoulos JC, Petrow P, Tanderup K, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO working group (IV): basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy. Radiother Oncol. 2012;103(1):113–22.PubMedPubMedCentralCrossRef Dimopoulos JC, Petrow P, Tanderup K, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO working group (IV): basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy. Radiother Oncol. 2012;103(1):113–22.PubMedPubMedCentralCrossRef
29.
go back to reference Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology group and the European Organization for Research and Treatment of Cancer. Int J Radiat Oncol Biol Phys. 1995;31:1341–6.PubMedCrossRef Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology group and the European Organization for Research and Treatment of Cancer. Int J Radiat Oncol Biol Phys. 1995;31:1341–6.PubMedCrossRef
30.
go back to reference Rose BS, Aydogan B, Liang Y, et al. Normal tissue complication probability modeling of acute hematologic Toxicity in cervical Cancer patients treated with Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(3):800–7.PubMedCrossRef Rose BS, Aydogan B, Liang Y, et al. Normal tissue complication probability modeling of acute hematologic Toxicity in cervical Cancer patients treated with Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(3):800–7.PubMedCrossRef
31.
go back to reference Japan Clinical Oncology Group1, Toita T, Ohno T, et al. A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer. Jpn J Clin Oncol. 2010;40(5):456–63.CrossRef Japan Clinical Oncology Group1, Toita T, Ohno T, et al. A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer. Jpn J Clin Oncol. 2010;40(5):456–63.CrossRef
32.
go back to reference Chao KS, Lin M. Lymphangiogram-assisted lymph node target delineation for patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;54(4):1147–52.PubMedCrossRef Chao KS, Lin M. Lymphangiogram-assisted lymph node target delineation for patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;54(4):1147–52.PubMedCrossRef
33.
go back to reference Klopp AH, Yeung AR, Deshmukh S, et al. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018;36:24.CrossRef Klopp AH, Yeung AR, Deshmukh S, et al. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018;36:24.CrossRef
34.
go back to reference Lujan AE, Mundt AJ, Yamada SD, et al. Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. Int Jof Radiat Oncol Biol Phys. 2003;57(2):516–21.CrossRef Lujan AE, Mundt AJ, Yamada SD, et al. Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. Int Jof Radiat Oncol Biol Phys. 2003;57(2):516–21.CrossRef
Metadata
Title
Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial
Authors
Jin Huang
Fei Gu
Tianlong Ji
Jing Zhao
Guang Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01606-3

Other articles of this Issue 1/2020

Radiation Oncology 1/2020 Go to the issue