Small-Cell Lung Cancer Long-Term Survivor Patients: How to Find a Needle in a Haystack?

Abstract

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by a rapid progression and a high resistance to treatments. Unlike other solid tumors, there has been a scarce improvement in emerging treatments and survival during the last years. A better understanding of SCLC biology has allowed for the establishment of a molecular classification based on four transcription factors, and certain therapeutic vulnerabilities have been proposed. The universal inactivation of TP53 and RB1, along with the absence of mutations in known targetable oncogenes, has hampered the development of targeted therapies. On the other hand, the immunosuppressive microenvironment makes the success of immune checkpoint inhibitors (ICIs), which have achieved a modest improvement in overall survival in patients with extensive disease, difficult. Currently, atezolizumab or durvalumab, in combination with platinum–etoposide chemotherapy, is the standard of care in first-line setting. However, the magnitude of the benefit is scarce and no predictive biomarkers of response have yet been established. In this review, we describe SCLC biology and molecular classification, examine the SCLC tumor microenvironment and the challenges of predictive biomarkers of response to new treatments, and, finally, assess clinical and molecular characteristics of long-term survivor patients in order to identify possible prognostic factors and treatment vulnerabilities.

A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC)

“…Of note, SCLC-I displays an immune-inflamed phenotype (the "I" stands for "inflamed"), possibly suggesting a heightened sensitivity to checkpoint inhibitors. [17]…”

Molecular clusters reveal opportunities for personalised small cell lung cancer immunotherapy

“…To the Editor: Small cell lung cancer (SCLC), which accounts for 15% of lung cancers, originated from the neuroendocrine (NE) lineage. 1,2 Relapse of the disease often occurs after traditional therapy, and chemo-immunotherapy is the new first line of treatment. 2 Currently, there is a lack of robust indicators to predict immunotherapy for SCLC.…”

“…1,2 Relapse of the disease often occurs after traditional therapy, and chemo-immunotherapy is the new first line of treatment. 2 Currently, there is a lack of robust indicators to predict immunotherapy for SCLC. 2 SCLC usually has higher tumour mutation burden (TMB) due to smoking and may benefit from immunotherapy.…”

“…2 SCLC usually has higher tumour mutation burden (TMB) due to smoking and may benefit from immunotherapy. 1,2 As known to all, high immunogenicity is reflected in both the tumour microenvironments (TME) (e.g., TMB and immunogenic cell death [ICD]). 2,3 A recent research has shown ICD genes were suppressed in SCLC, we are interested in whether there is a highly immunogenic SCLC group to receive immunotherapy.…”

Deep Learning Facilitates Distinguishing Histologic Subtypes of Pulmonary Neuroendocrine Tumors on Digital Whole-Slide Images

“…LCNEC patients frequently develop local and systemic metastases, and the cure rate and overall prognosis are dismal, with 5-year survival rates of 13–57% for all patients, 27–62% for early-stage patients and only 5% for late-stage patients [ 7 ]. Most patients are diagnosed with extensive disease SCLC and, due to the aggressive behavior of this disease, have a median overall survival between 9 and 12 months [ 8 ].…”