Lung cancer screening: a critical appraisal.

PURPOSE OF REVIEW: The recently published large-scale NELSON trial showed a reduction in lung cancer (LC) mortality with the use of low-dose computed tomography (LDCT) in high-risk patients. This is the first such European-based trial to mirror the results of the US National Lung Screening Trial (NLST). The NLST was responsible for nationwide implementation of LC screening protocols which has shown a decrease in LC mortality. However, the implementation of such screening in Europe has been challenging. With the findings from the NELSON trial, implementation of LC screening throughout Europe should once again be evaluated. RECENT FINDINGS: This review article further elaborates on the advantages of LDCT in LC screening. It also discusses promising future approaches that can supplement the current LC screening guidelines. SUMMARY: Implementation of LC screening with LDCT should again be evaluated throughout Europe as it could substantially decrease LC-related mortality.

Intravenous immunoglobulin efficacy on pembrolizumab induced severe toxic epidermal necrolysis.

Pembrolizumab is an immune checkpoint inhibitor used in many different cancers. Several immune-related adverse events (irAEs) have been associated with pembrolizumab, including toxic epidermal necrolysis. Here, we are presenting a patient with non-small cell lung cancer that developed toxic epidermal necrolysis 3-days following initiation of pembrolizumab. Following high-dose steroid therapy, intravenous immunoglobulin 2 g/kg was initiated and resulted in complete resolution of all his irAEs. To our knowledge, this is the first reported case of total re-epithelialization and resolution of immune checkpoint inhibitor-induced toxic epidermal necrolysis following the use of intravenous immunoglobulin.

Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Existing data on adding internal mammary nodal irradiation (IMNI) to the regional nodal fields are inconsistent. Methods: Randomized trials investigating the addition of IMNI to standard adjuvant radiation were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall-survival (OS), breast cancer specific-survival (BCSS), and disease-free survival (DFS) as well as distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer, and cardiovascular morbidity and mortality were also extracted. Results: Analysis included five trials comprising 10,994 patients, predominantly with higher risk, lymph node positive disease. Compared to the control group, IMNI was associated with significant improvement in OS (HR = 0.91, p = 0.004), BCSS (HR = 0.84, p < 0.001), DFS (HR = 0.89, p= 0.01), and DMFS (HR = 0.89, p = 0.02). IMNI was also associated with reduced odds for regional (OR = 0.58, p < 0.001) and loco-regional recurrence (OR = 0.85, p = 0.04). The odds for cardiotoxicity were not statistically significantly higher (OR = 1.23, p = 0.07). There were comparable odds for cardiovascular mortality (OR = 1.00, p = 1.00), non-breast cancer mortality (OR = 1.05, p = 0.74), secondary cancer (OR = 0.95, p = 0.51), and contra-lateral breast cancer (OR = 1.07, 95% 0.77−1.51, p = 0.68). Conclusions: Compared to the control group, the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness.

Real-world efficacy and safety of mobocertinib in EGFR exon 20 insertion-mutated lung cancer.

Background: Non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions (EGFRex20ins) is relatively resistant to the existing EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is a novel TKI that selectively targets EGFRex20ins and has demonstrated therapeutic efficacy in pretreated patients with tumors harboring these mutations. Methods: This is a retrospective, non-interventional, multicenter real-world study aimed at assessing the efficacy and safety of mobocertinib in patients with EGFRexon20ins who received 160 mg QD monotherapy as part of expanded access. Data collection was based on patients' records. PET-CT or CT scans were used to measure systemic response, while brain MRIs were used to examine intracranial response as part of the follow-up. Results: 16 patients were included in this report. Mobocertinib was administered to 31.3% (5) of patients as first-line, 50% (8) as second-line, and 18.7% (3) as a later-line therapy. The median age was 65 years (range, 38-83), 75% (12/16) were female, and 50% (8/16) had brain metastases at baseline before mobocertinib treatment. The objective response rate (ORR) to mobocertinib was 25% (4/16) (1/5 for first line and 3/11 for other lines), disease control rate (DCR) was 75% (12/16) with a follow-up period of 11 months. The median duration of treatment (mDoT) was 5.6 months across all patients, and 8.6 months in responders. Based on the presence or absence of brain metastasis, the mDoT was 14.8 and 5.4 months (p=0.01), respectively. Mobocertinib Grade ≥3 treatment-related adverse events (TRAEs) included diarrhea (19%), nausea (6%) and renal failure (6%). Dose reduction was reported in 25% of cases to 80 mg. Conclusion: Mobocertinib in compassionate use exhibited an ORR of 25%, which is very similar to that of the phase 2 EXCLAIM study and clearly better than historical data of monochemotherapy or conventional EGFR inhibitors. The greatest benefit was noted in patients without brain metastases, who showed durable effects with mDoT 14.8 months, while intracranial activity was limited. These findings may assist therapeutic considerations, inasmuch as results from the EXCLAIM cohort-3 dedicated to brain lesions are not available yet.

Safety of the BNT162b2 mRNA COVID-19 vaccine in oncologic patients undergoing numerous cancer treatment options: A retrospective single-center study.

ABSTRACT: The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy.This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships.Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died.The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.