Severity of bleomycin-induced lung toxicity in Indian patients with intermediate and poor-risk non-seminomatous germ cell tumors (NSGCT): A clinical perspective.
Authors: Gujarathi Himanshu , Dhanawat Aditya , Jadhav Bhagyashri , Tiwari Atul , Jobanputra Kunal Naishadh , YC Kriti , Rane Pallavi , Shah Minit Jalan , Menon Nandini Sharrel , Maitre Priyamvada , Pal Mahendra , Arora Amandeep , Ringe-Katdare Aparna , Menon Santosh , Prakash Gagan , Murthy Vedang , Noronha Vanita , Prabhash Kumar , Tandon Saneep , Joshi Amit 
Published: February 2025

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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%)