TREATMENT-INDUCED PULMONARY TOXICITY IN PATIENTS WITH MEDULLOBLASTOMA: A RETROSPECTIVE ANALYSIS ON 2 ITALIAN INSTITUTIONS' COHORTS

Abstract BACKGROUND: Incidence of iatrogenic pulmonary toxicity is around 20%. Apart from bleomycin fibrosis, the role of lomustine, HD-thiotepa, autologous stem-cells transplantation(APBSCT) and their synergy with craniospinal irradiation(CSI) are unclear. To elucidate their role in lung-function impairment, we retrospectively evaluated 39 medulloblastoma patients treated at INT-Milan and OPBG-Rome. METHODS: 39 patients (17 females, median RT age 8 years) treated for localized(29) or metastatic(10) medulloblastoma in 2000-2020 and with spirometric assessment, were considered. Treatment included: SIOP-like-PNET IV(19), high-risk protocol(19), infant protocol without RT(1). CSI doses were: 23.4Gy(20), 31.2Gy(8), 36Gy(6) and 39Gy(4); 4 received protons and 34 photons(9 VMAT, 25 3D), 11 hyperfractionated-accelerated-RT; 33 had 6 median CCNU cycles; 6 APBSCT. RESULTS: Median follow-up: 98 months. All patients performed at least one spirometry at median 5 years after RT. Eight (20.6%) had mildly pathological spirometries, 8 Forced Vital Capacity (FVC%)<90%. RT age was not associated with FVC%/ PEF% (p=0.319 and 0.405). A lower Peak Expiratory Flow(PEF%) was marginally associated to APBSCT group (p=0.062) with FVC%(≤90% vs >90%) similar but less significant(p=0.163). Median FVC%/PEF% were higher in the CCNU-group without reaching significance (p=0.436 and 0.062): this was a standard-risk group not receiving APBSCT nor higher RT doses. Even though the lung volume encompassed by 5-10 Gy isodoses was greater in VMATvs3D RT(p<0.001 and p=0.015), there were no significant differences in ventilatory parameters. FVC%/PEF% were negatively associated to CSI dose. Since no relevant lung volume is involved in high doses, a multifactorial etiology could be speculated. CONCLUSIONS: Preliminary data show no significant FVC%/PEF% reduction. Small sample size and differences in spirometry techniques impose larger cohorts accrual to elucidate potential treatment-induced pulmonary impairment in the pediatric population thus validating the use of spirometry during treatment/follow-up.