Vol 29, No 3 (2024)
Research paper
Published online: 2024-06-18

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Dynamics and predictors of hematologic toxicity during cranio-spinal irradiation

Andrada Turcas12, Bianca Homorozeanu21, Cristina Gheara31, Cristina Balan31, Rodica Cosnarovici4, Oana Diaconu31, Zsolt Fekete12, Emilia Mihut4, Diana Olteanu4, Paula Pruteanu4, Alexandru Tipcu21, Adrian Turcas5, Dana Cernea1, Daniel Leucuta6, Patriciu Achimas-Cadariu27
DOI: 10.5603/rpor.101094
Rep Pract Oncol Radiother 2024;29(3):362-372.

Abstract

Background: Craniospinal irradiation (CSI) is a complex radiotherapy (RT) technique required for treating specific brain tumors and some hematologic malignancies. With large volumes of hematogenous bone marrow (BM) being irradiated, CSI could cause acute hematologic toxicity, leading to treatment interruptions or severe complications. We report on the dynamics and dose/volume predictors of hematologic toxicity during CSI.

Material and methods: Pediatric patients (≤ 18years) undergoing CSI in a tertiary cancer center were included. Medical records were retrospectively reviewed for clinical data and blood parameters were collected at baseline and weekly, until four weeks after the end of RT. The BM substructures were contoured, and dose-volume parameters were extracted. We used Wilcoxon rank-sum test to compare quantitative data, Chi square test for qualitative data and receiver operating characteristics (ROC) curves for dose/volume thresholds.

Results: Fifty-one patients were included. Severe toxicities (grade 3–4) were recorded as follows: 2% anemia, 8% thrombocytopenia, 25% leukopenia, 24% neutropenia. Ninety-eight percent of patients had lymphopenia (grade 1–4) at some point. Twenty-nine percent required granulocyte-colony stimulating factor, 50% had an infection and 8% required a blood transfusion.

Dmean > 3.6 Gy and V15 Gy > 10.6% for Pelvic Bones were associated with a higher risk of developing any ≥ G3 toxicities. Dmean > 30-35Gy to the Thoracic and Lumbar spine was predictive for G3–4 anemia and thrombocytopenia, and Cervical Spine Dmean > 30 Gy was associated with ≥ G3 neutropenia.

Conclusion: CSI was well tolerated, without life-threatening complications in our cohort, but hematologic toxicity was frequent, with severity increasing with higher mean doses delivered to the hematogenous BM and larger volumes of BM receiving 30–35 Gy.

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References

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  45. Krishnatry R, Gudi S, Siwach A, et al. Impact of immobilisation and image guidance protocol on planning target volume margins for supine craniospinal irradiation. Rep Pract Oncol Radiother. 2022; 27(2): 250–259.
  46. Lopez Guerra JL, Marrone I, Jaen J, et al. Outcome and toxicity using helical tomotherapy for craniospinal irradiation in pediatric medulloblastoma. Clin Transl Oncol. 2014; 16(1): 96–101.
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  51. Chang CW, Goette M, Kadom N, et al. Early in vivo Radiation Damage Quantification for Pediatric Craniospinal Irradiation Using Longitudinal MRI for Intensity Modulated Proton Therapy. Adv Radiat Oncol. 2023; 8(5): 101267.
  52. Paulino AC, Wen BC, Mayr NA, et al. Protracted radiotherapy treatment duration in medulloblastoma. Am J Clin Oncol. 2003; 26(1): 55–59.
  53. Jefferies S, Rajan B, Ashley S, et al. Haematological toxicity of cranio-spinal irradiation. Radiother Oncol. 1998; 48(1): 23–27.
  54. Barney CL, Brown AP, Grosshans DR, et al. Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. Neuro Oncol. 2014; 16(2): 303–309.
  55. Fernández KS, de Alarcón PA. Development of the hematopoietic system and disorders of hematopoiesis that present during infancy and early childhood. Pediatr Clin North Am. 2013; 60(6): 1273–1289.
  56. Campbell BA, Callahan J, Bressel M, et al. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning. Int J Radiat Oncol Biol Phys. 2015; 92(5): 1035–1043.
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  61. Paulino A, Suzawa H, Dreyer Z, et al. Scoliosis in children receiving craniospinal irradiation for medulloblastoma. Pediatr Blood Cancer. 2015; 62: S209.
  62. Turcas A, Kelly SM, Bernier-Chastagner V, et al. Management of the vertebrae as an organ at risk in paediatric radiotherapy clinical trials: Initial QUARTET experience. Radiother Oncol. 2023; 187: 109810.
  63. Yoon M, Shin DHo, Kim J, et al. Craniospinal irradiation techniques: a dosimetric comparison of proton beams with standard and advanced photon radiotherapy. Int J Radiat Oncol Biol Phys. 2011; 81(3): 637–646.
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  65. Yu DY, Bai YL, Feng Y, et al. Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer? Front Oncol. 2020; 10: 554241.
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  67. Singareddy R, Bajwa HK, Reddy MM, et al. Dosimetric predictors of acute bone marrow toxicity in carcinoma cervix - experience from a tertiary cancer centre in India. Rep Pract Oncol Radiother. 2021; 26(2): 259–265.
  68. Chou B, Hopper A, Elster J, et al. Volumetric De-Escalation and Improved Acute Toxicity with Proton Craniospinal Irradiation Using a Vertebral Body Sparing Technique. Pediatr Blood Cancer. 2022; 69(5): e29489.
  69. Yu DY, Bai YL, Feng Y, et al. Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer? Front Oncol. 2020; 10: 554241.
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  71. Chang EL, Allen P, Wu C, et al. Acute toxicity and treatment interruption related to electron and photon craniospinal irradiation in pediatric patients treated at the University of Texas M. D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys. 2002; 52(4): 1008–1016.
  72. Kumar N, Miriyala R, Thakur P, et al. Impact of acute hematological toxicity on treatment interruptions during cranio-spinal irradiation in medulloblastoma: a tertiary care institute experience. J Neurooncol. 2017; 134(2): 309–315.
  73. Lőcsei Z, Farkas R, Borbásné Farkas K, et al. Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years. BMC Cancer. 2020; 20(1): 702.
  74. Wong KK, Ragab O, Tran HN, et al. Acute toxicity of craniospinal irradiation with volumetric-modulated arc therapy in children with solid tumors. Pediatr Blood Cancer. 2018; 65(7): e27050.
  75. Vennarini S, Del Baldo G, Lorentini S, et al. Acute Hematological Toxicity during Cranio-Spinal Proton Therapy in Pediatric Brain Embryonal Tumors. Cancers (Basel). 2022; 14(7).
  76. Gandola L, Massimino M, Cefalo G, et al. Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol. 2009; 27(4): 566–571.
  77. Madan R, Kumar N, Gupta A, et al. Effect of prophylactic granulocyte-colony stimulating factor (G-CSF) on acute hematological toxicity in medulloblastoma patients during craniospinal irradiation (CSI). Clin Neurol Neurosurg. 2020; 196: 105975.
  78. Jin JY, Mereniuk T, Yalamanchali A, et al. A framework for modeling radiation induced lymphopenia in radiotherapy. Radiother Oncol. 2020; 144: 105–113.
  79. So TH, Chan SK, Chan WL, et al. Lymphopenia and Radiation Dose to Circulating Lymphocytes With Neoadjuvant Chemoradiation in Esophageal Squamous Cell Carcinoma. Adv Radiat Oncol. 2020; 5(5): 880–888.
  80. Yoo GS, Yu JIl, Cho S, et al. Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors. Cancer Res Treat. 2022; 54(3): 907–916.