Dynamics and predictors of hematologic toxicity during cranio-spinal irradiation

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.

Materials 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 > 30-35 Gy 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.

Keywords: craniospinal irradiation; medulloblastoma; pediatric oncology; radiotherapy; toxicity.

Figure 1

A. Bone marrow segments contoured for each patient. B. Typical dose distribution overlayed on the bone marrow volume and Example cases of three different treatment plans of cranio-spinal irradiation and tumour bed boost within the posterior fossa: C. 3D conformal with three isocentres, two lateral opposed fields for the cranial segment and two posterior fields for the superior and the inferior spinal levels, respectively; D. Volumetric modulated arc therapy VMAT with three isocentres and three complete arcs; vertebral bodies were included in the prescribed craniospinal irradiation (CSI) dose E. Helical tomotherapy (HT) plan with continuous, helical dose distribution for a post-pubertal patient; vertebral bodies were not included in the prescribed dose (all patients received 23.4 Gy on the cranio-spinal axis with up to 54 Gy to the boost volume)

Figure 2

A. Dynamics of blood counts at different timepoints. preRT — before the start of radiotherapy; W1–6 — first to sixth week of irradiation; postRT w1–4 — first to forth week after the end of radiotherapy; Ne — neutrophils; Hb — haemoglobin; TBC — thrombocytes; WBC — white blood cells; Ly — lymphocytes; B. Box plots showing V5–V40 Gy for each contoured structure. All values are expressed in percentage (%) from the total structure volume; V5 — volume (%) receiving 5 Gy; V10 — volume (%) receiving 10 Gy; V15 — volume (%) receiving 15 Gy; V20 — volume (%) receiving 20 Gy; V25 — volume (%) receiving 25 Gy; V30 — volume (%) receiving 30 Gy; V35 — volume (%) receiving 35 Gy; V40 — volume (%) receiving 40 Gy