Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy - single institute experience.

BACKGROUND: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine. PATIENTS AND METHODS: We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients. RESULTS: Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12-99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5-12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2-80.8%) and 45.8% (95% CI: 32.7-58.9%). With the median follow-up time of 23 months (range 2-35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5-93.9%) and 68.6% (95% CI: 57.2-79.9%). CONCLUSIONS: Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.

Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence.

BACKGROUND: Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence. PATIENTS AND METHODS: In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model. RESULTS: Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer. CONCLUSIONS: We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.

Genotyping of BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes in a male patient with secondary breast cancer.

BACKGROUND: Some tumour suppressor genes (BRCA2) and mismatch repair genes (MSH2, MLH1) are correlated with an increased risk for male breast cancer. CASE REPORT: Our patient developed secondary breast cancer after the treatment for Hodgkin's disease in childhood. DNA was isolated from the patients' blood and screened for mutations, polymorphisms and variants in BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes. We found no mutations but common polymorphisms, and three variants in mismatch repair genes. CONCLUSIONS: Nucleotide variants c.2006-6T>C and p.G322D in MSH2 might be correlated with male breast cancer.