ALBA project: prognostic impact of laterality in small-cell lung cancer

Resuli, Blerina (2025): ALBA project: prognostic impact of laterality in small-cell lung cancer. Dissertation, LMU München: Medizinische Fakultät

Abstract

Importance: SCLC remains among the most therapeutically challenging thoracic malignancies, marked by rapid progression, high metastatic potential, and limited long-term survival. Established prognostic factors—such as performance status, tumor stage, and liver metastases—are important but insufficient for accurate patient stratification. This gap highlights the need for new, clinically meaningful markers that could guide individualized treatment decisions. Objective: Recent studies in well-differentiated pulmonary neuroendocrine tumors have shown that the side of tumor origin (laterality) can influence prognosis, with worse outcomes reported for left-sided carcinoids. Given the neuroendocrine lineage of SCLC, albeit poorly differentiated, we hypothesized that tumor laterality might similarly affect survival in SCLC. Our study aimed to assess whether the side of the lung in which the primary tumor develops serves as a prognostic indicator, potentially reflecting underlying biological variation. Design, Setting, and Participants: This was a multicenter, retrospective, observational study involving three institutions—two in Italy and one in Germany. The cohort included consecutive patients diagnosed with histologically or cytologically confirmed SCLC, treated between January 2020 and December 2022, and followed for a minimum of three months. Treatment approaches varied according to disease stage and institutional standards. Main Outcomes and Measures: We collected comprehensive clinical and pathological data, including patient demographics, tumor characteristics (location, histology, stage), metastatic spread, and treatment details. The key outcome measures were PFS and OS. We evaluated the prognostic impact of tumor laterality in the context of other clinical variables such as age, sex, ECOG performance sta-tus, metastatic sites, and therapy received. Results: A total of 222 patients were included in the analysis. The cohort was predominantly male (60.4%) and comprised a high proportion of individuals with a smoking history (90.1%). Most patients were diagnosed with advanced disease, with 75.2% at stage IV. Tumors were almost equally distributed between the lungs: 49.5% in the right and 50.5% in the left. Consistent with existing literature, poorer survival was observed in patients with advanced stage, poor ECOG status, and liver metastases at diagnosis. Notably, our study found that tumor laterality independently influenced prognosis. Patients with right-sided tumors had significantly better median OS than those with left-sided tumors (12 vs. 8 months, p = 0.001; HR = 2.020). A similar pattern was ob-served for PFS: right-sided tumors had a median PFS of 7.8 months, compared to 6.7 months for left-sided tumors (p = 0.009; HR = 1.293). Additional prognostic factors identified included smoking status, ECOG performance score, and the presence of distant lymph node or bone metastases. In contrast, no significant association was found between OS or PFS and patient sex, or metastases to the brain, lung, adrenal glands, or pleura. Conclusions and Relevance: Our findings suggest, for the first time in the context of SCLC, that the location of the primary tumor may hold prognostic value. This observation is in line with previous work on lung carcinoids, and may reflect biological differences between the left and right pulmonary environments. As La Salvia et al. noted in lung NETs, “tumor laterality was associated with necrosis, angiogenesis, and microenvironmental differences, contributing to survival disparities” [La Salvia et al., 2021]. We hypothesize that differential exposure to inhaled carcinogens, asymmetric lymphatic drainage, or variations in local hypoxia may contribute to this effect. These findings support the need for further research into how anatomical and molecular tumor characteristics interact, and whether tumor laterality could be integrated into prognostic models or used as a stratification factor in clinical trials.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: small-cell lung cancer, laterality, prognostic
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 18. Dezember 2025
• 1. Bericht­erstatter:in: Tufman, Amanda