Etoposide/ifosfamide

Abstract

Primary lung adenocarcinoma: 2 case reports In a case series of three patients, two patients (1 girl and 1 boy) aged 8 years and 12 years were described, who developed primary lung adenocarcinoma following treatment with etoposide and ifosfamide for Ewing sarcoma [routes and dosages not stated; time to reaction onsets not clearly stated]. An 8-year-old girl (case 1 from the article) was diagnosed with Ewing sarcoma in January 2012. She received 6 cycles of unspecified neoadjuvant chemotherapy followed by a surgery. Histologically, complete response was observed. Thereafter, she received 3 cycles of adjuvant chemotherapy with etoposide and ifosfamide [iphosphamide]. However, 7 months later, a control thoracic CT showed multiple bilateral lung nodules. The girl was treated with unspecified chemotherapy for several months. Thereafter, a control CT revealed reduction in size and number of pulmonary nodules. Nineteen months after initial diagnosis, she was hospitalised and wedge resection of right and left pulmonary nodules (without regional lymph node dissection) was performed in two separate operations with removal of 5 and 4 nodules from the right and left lung, respectively. Four months later, total lung irradiation was performed. Five lung fragments, sized 3cm each, were resected from the right lower lobe and histological evaluation was performed. A nodule in one of the fragments was a 4mm epithelial proliferation with a predominantly lepidic growth pattern characterised by an abrupt transition from the surrounding normal alveolar cells. At higher magnification, the lepidic proliferation was noted to have crowded, plumped cuboidal cells with mild cytological atypia. No signs of stromal invasion were observed. Ki67 immunohistochemistry demonstrated a proliferative index of 9% in atypical epithelial cells. Based on these findings, a diagnosis of primary lung adenocarcinoma was considered. Gene mutation analysis of resected specimen revealed presence of two mutations on EGFR gene: a common activating exon 19 deletion (p.E746_A750, COSMIC 6225) (VAF=17.6%) and an uncommon exon 20 insertion (p.D770>GY, COSMIC 12427) (VAF=25.4%). Both alterations were in the tyrosine kinase (TK) domain, leading to a gain of function of the membrane receptor. Furthermore, a PIK3CA point mutation (p.R412Q) was also found with VAF=5.6%. This mutation occurred in the C2 protein domain. Chemotherapy with etoposide and ifosfamide was suspected to have contributed in the development of primary lung adenocarcinoma. She was noted to be free of disease at 99 months after Ewing Sarcoma diagnosis and 91 months after lung adenocarcinoma resection. A 12-year-old boy (case 2 from the article) was diagnosed with Ewing sarcoma in August 2011. He received 3 cycles of unspecified neoadjuvant chemotherapy. Three months later, he underwent surgery with left proximal femur resection and prosthesis. Histologically, a complete response was observed. Thereafter, he received 3 cycles of adjuvant chemotherapy with etoposide and ifosfamide [iphosphamide] for 4 months. After 2 years, during a follow-up, a thoracic CT showed a left lower lobe lung nodule. Another separate small (5mm) nodule was radiologically observed in the same pulmonary lobe. The former nodule appeared to increase in volume in x-ray investigations. Therefore, 38 months of the initial diagnosis of Ewing sarcoma, the boy was hospitalised and a left lower lung lobectomy was performed. A 5mm nodule was removed from the left lower lobe and histological evaluation was performed. A neoplastic epithelial proliferation with a lepidic predominant (90%) and focal acinar (10%) growth pattern was noted. This latter component demonstrated small-to-medium-sized glandular structures, lined by columnar cells with mild cytological atypia. The stromal invasive component was less than 5mm. He was diagnosed with minimally invasive primary lung adenocarcinoma, pT1a(mi) N0, stage IA1. Gene mutation analysis of resected specimen revealed presence of a single EGFR exon 20 insertion/duplication (p.N771_H773DUP, COSM 12381) (VAF=15.4%). Two months after left lower lung lobectomy, he received radiotherapy as consolidation treatment. He was noted to be free of disease at 112 months after Ewing Sarcoma diagnosis and 74 months after lung adenocarcinoma resection.