Severity of bleomycin-induced lung toxicity in Indian patients with intermediate and poor-risk non-seminomatous germ cell tumors (NSGCT): A clinical perspective.

635 Background: Bleomycin, etoposide and cisplatin (BEP) chemotherapy is the standard of care in advanced NSGCT due to its extremely high efficacy. The incidence of bleomycin-induced lung toxicity ranges between 5-40%. Risk factors include older patients, smokers, pre-existing lung diseases, cumulative dose > 300 units and previous radiation to thorax. Methods: This was a retrospective analysis of a prospectively collected dataset of intermediate and poor risk NSGCT patients treated with BEP at a comprehensive cancer care centre in India. Adolescent and adult males with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who developed bleomycin-induced lung toxicity were included. Descriptive analyses were performed and Kaplan-Meier method was used for estimation of survival using SPSS version 29.0. Results: A total of 223 patients with intermediate and poor risk NSGCT received BEP, of which 30 (13%) developed bleomycin induced lung toxicity and were included in this analysis. The median age was 31.5 years (IQR: 25.75 - 34.5 years) (Table). Twenty-eight (93.3%) were non-smokers while 14 (46.7%) did not have lung metastases. Six (20%) had baseline serum creatinine > 1.3mg/dL. Twelve (40%) required granulocyte colony stimulating factor (G-CSF). The median baseline forced vital capacity (FVC) was 3.88 L while diffusing capacity of lung for carbon monoxide (DLCO) was 90%. Post BEP, the median FVC was 2.76 L while DLCO was 68% among those who had lung toxicity. Seventeen (56.7%) were symptomatic for lung toxicity while 13 (43.3%) had grade 1 pneumonitis. Eighteen (60%) received 4 cycles of BEP, 8 (26.7%) received 3 cycles while 4 (13.3%) received 2 cycles prior to developing lung toxicity. Seven (23.3%) required hospitalization of which 6 (20%) had hospital stay for more than 10 days, 5 (16.7%) required ambulatory oxygen and 4 (13.3%) required intensive care. Nineteen (63.3%) required steroids. Five (16.7%) died due to bleomycin-induced lung toxicity. With a median follow-up of 81 months, the 5-year and 10-year OS were 61.6% and 55.5% respectively. Conclusions: The potential of bleomycin to cause lung toxicity necessitates careful patient selection, monitoring and optimal management. Patient characteristics. Characteristics All patients(n = 30) Age group Less than 35 years 23 (76.7%) More than or equal to 35 years 7 (23.3%) Primary site Testis 28 (93.4%) Retro-peritoneum 1 (3.3%) Mediastinum 1 (3.3%) Risk stratification Intermediate 15 (50%) Poor 15 (50%) Lung metastases None 14 (46.7%) Unilateral 3 (10%) Bilateral 13 (43.3%) Grade of pneumonitis (CTCAE v5.0) Grade I 13 (43.3%) Grade II 10 (33.3%) Grade III 2 (6.7%) Grade IV 0 Grade V 5 (16.7%) CT chest findings Air-space consolidation 1 (3.3%) Ground glass or nodular opacities 10 (33.3%) Reticular interstitial thickening 14 (46.7%) Fibrotic changes 5 (16.7%)