Consolidation Systemic Therapy in Locally Advanced, Inoperable Nonsmall Cell Lung Cancer-How to Identify Patients Which Can Benefit from It?

BACKGROUND: Consolidation systemic therapy (ST) given after concurrent radiotherapy (RT) and ST (RT-ST) is frequently practiced in locally advanced inoperable nonsmall cell lung cancer (NSCLC). Little is known, however, about the fate of patients achieving different responses after concurrent phases of the treatment. METHODS: we searched the English-language literature to identify full-length articles on phase II and Phase III clinical studies employing consolidation ST after initial concurrent RT-ST. We sought information about response evaluation after the concurrent phase and the outcome of these patient subgroups, the patterns of failure per response achieved after the concurrent phase as well as the outcome of these subgroups after the consolidation phase. RESULTS: Eighty-seven articles have been initially identified, of which 20 studies were excluded for various reasons, leaving, therefore, a total of 67 studies for our analysis. Response evaluation after the concurrent phase was performed in 36 (54%) studies but in only 14 (21%) response data were provided, while in 34 (51%) studies patients underwent a consolidation phase regardless of the response. No study provided any outcome (survivals, patterns of failure) as per response achieved after the concurrent phase. CONCLUSIONS: Information regarding the outcome of subgroups of patients achieving different responses after the concurrent phase and before the administration of the consolidation phase is still lacking. This may negatively affect the decision-making process as it remains unknown which patients may preferentially benefit from the consolidation of ST.

Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer.

INTRODUCTION: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC. MATERIALS AND METHODS: Patients with RR SCLC and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m2 intravenous (IV)/irinotecan 350 mg/m2 IV (day 1), irinotecan 350 mg/m2 IV (day 1), or topotecan 1.5 mg/m2 IV (days 1-5) in 21-day cycles. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed. RESULTS: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (≥5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia. CONCLUSIONS: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily × 5 every 21 days. CLINICALTRIALS: gov Identifier. NCT03098030.

Real-World Treatment Patterns of Lung Cancer in a Resource-Restricted Country: the Experience of Georgia.

Lung cancer (LC) is the most common malignancy responsible for 1.8 million of deaths worldwide. Lung and bronchus cancer represents 13% (n = 1217) of all new cancer cases in Georgia. In 2018, in Georgian males lung cancer age-standardized incidence rate was 35.7/per 100 000, less compared to regional countries as Turkey (70.6), Russia (48.2), Ukraine (41.7), and Armenia (58.5), but higher than in neighbor Azerbaijan (25.5). Incidence is higher compared to central and eastern Europe (27.3) and near similar to North America (34.5). Georgia is an Eastern European, middleincome country with 3.7 million residents and one of the highest numbers of active smokers in the European Region. The Georgian health care system is divided into a public and a private sector, with coverage of nearly 100% of the population. There is a national healthcare system as well as private insurance and all patients, irrespective of insurance (private or governmental) can choose the hospital for treatment by themselves all over the country. The Basic Package of the Universal Health Care Program includes the treatment of oncologic patients, specifically surgery, chemotherapy, hormone therapy and radiotherapy and investigations and medications related to these procedures. The program covers all types of laboratory and instrumental investigations related to planned treatment. Georgia lacks an LC screening program for smokers and partially because of this, the majority of patients with lung cancer present at an advanced stage. The National Centre for the Disease Control (NCDC) showed that almost 90% of LC patients in the country present with advanced stages (III-IV) with 60% of patients having stage IV disease at diagnosis . Lung cancer is generally diagnosed at an advanced stage. For non-small cell lung cancer (NSCLC), the proportion with metastatic disease (TNM stage IV) ranged from 46.8% to 61.2% in developed countries. In recent years, there have been several publications addressing specifics of LC worldwide, but none concerning Georgia. In light of the rapidly changing landscape in the diagnosis, staging, and treatment of LC, we thought to define the state of practice in Georgia by convening specialists who treat LC across 13 institutions in our country with the goal to describe differences in access and approaches to LC.

Neuroendocrine pancreatic tumor in a patient with dual diagnosis of tuberous sclerosis complex and basement membrane disease: A case report and review of the literature.

Tuberous Sclerosis is a complex genetic disease that has well-defined clinical criteria. These criteria don't include pancreatic neuroendocrine tumors. We represent a rare case of a patient, with a non-functioning pancreatic neuroendocrine tumor and concomitant diagnosis of tuberous sclerosis complex, and basement membrane disease. The patient was diagnosed based on typical radiologic findings. We have suggested close monitoring and during follow-up studies, the disease was stable. Interestingly the patient tested negative for Tuberous Sclerosis Complex (TSC), which suggests that she might be a somatic mosaic and the mutation level in blood lymphocytes was below the detection level. Moreover, a heterozygous pathogenic variant p.(Gly774Arg) and a heterozygous likely pathogenic variant p.(Gly1465Asp) were identified in the COL4A4 gene. COL4A4 gene is responsible for causing autosomal dominant basement membrane disease. In this case report, we discuss clinical, radiologic, and genetic aspects of these diseases, as well as optimal treatment and follow-up strategies. Thus, by presenting this case we would like to increase awareness of pancreatic neuroendocrine tumors in TSC and emphasize the need for follow-up monitoring.

Molecular profiling and characteristics of non-small-cell lung cancer patients in Georgia.

Aims: In patients with advanced non-small-cell lung cancer, the correlation between histopathology, smoking status, driver oncogene mutations and PD-L1 overexpression were investigated. Patients and methods: A total of 202 patients were identified. Research was done in Georgia. Results: EGFR mutations were detected in 6% of the tested cases (12/187) and five out of 12 EGFR+ cases had histology consistent with squamous cell carcinoma. No statistically significant correlation was observed between PD-L1 expression, smoking status and clinicopathological characteristics. However, the correlation between smoking status and histology was statistically significant (p = 0.0264), as never-smokers had a higher incidence of adenocarcinoma histology. Conclusion: The study showed a small percentage of EGFR mutations associated with adenocarcinoma histology and revealed a solid existence of this mutation in squamous cell carcinoma histology. A higher incidence of adenocarcinoma histology was observed in never-smokers.