Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Extended Delay to Treatment for Stage III-IV Non-Small-Cell Lung Cancer and Survival: Balancing Risks During the COVID-19 Pandemic.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, patients may encounter lung cancer care delays. Here, we sought to examine the impact of extended treatment delay for stage III-IV non-small-cell lung cancer on patient survival. MATERIALS AND METHODS: Using National Lung Screening Trial (NLST) and National Cancer Data Base (NCDB) data, Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage III-IV lung adenocarcinoma and squamous cell carcinoma. In the NCDB, propensity score-matched analysis was used to compare cumulative survival in patients who received "early" versus "delayed" treatment (ie, 0-30 vs. 90-120 days following diagnosis). RESULTS: Cox regression analysis of the NLST (n = 392) and NCDB (n = 275,198) cohorts showed a decrease in hazard ratio the longer treatment was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed treatment for patients with stage IIIA, IIIB (T3-4,N2,M0), IIIC, and IV (M1B-C) adenocarcinoma and patients with IIIA, IIIB, IIIC, and IV squamous cell carcinoma (all log-rank P > .05). For patients with stage IIIB (T1-2,N3,M0) and stage IV (M1A) adenocarcinoma, delayed treatment was associated with improved survival (log-rank P = .03, P = .02). The findings were consistent in sensitivity analysis accounting for wait time bias. CONCLUSION: In this national analysis, for patients with stage III-IV adenocarcinoma and squamous cell carcinoma, an extended treatment delay by 3 to 4 months was not associated with significantly decreased overall survival compared to prompt treatment. These findings can be used to guide decision-making during the ongoing COVID-19 pandemic.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as mortality predictor of advanced stage non-small cell lung cancer (NSCLC) with COVID-19 in Indonesia.

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Long-term Overall Survival Outcomes in Patients with Early Stage, Peripherally Located, Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiotherapy in a Non-academic Cancer Centre.

AIMS: To report long-term outcomes of patients treated with stereotactic ablative radiotherapy (SABR) for early stage, peripherally located non-small cell lung cancer. MATERIALS AND METHODS: Data were collected retrospectively between September 2009 and May 2019. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. All patients were treated according to local protocol based on the national UK SABR Consortium guidelines. Risk-adapted treatment schedules were used depending on the size and the location of the tumour (54 Gy in three fractions, 55 Gy in five fractions, 60 Gy in eight fractions or 50 Gy in 10 fractions). Overall survival outcomes were evaluated using the Kaplan-Meier method. RESULTS: In total, 412 patients were included in the analysis. The median age was 76 years (range 48-93 years). Histological confirmation was obtained in 233 cases (56.6%). The median overall survival for all patients was 42.3 months (95% confidence interval 37.3-47.3 months), with 3- and 5-year overall survival of 52.8% and 37.3%, respectively. For biopsy-proven patients (56.6%), 3- and 5-year overall survival was 57.3% and 40.1%, respectively. With respect to overall survival, univariate and multivariate analysis revealed no significant difference in survival by technique (volume-modulated arc therapy versus conformal; three-dimensional computed tomography versus four-dimensional computed tomography), tumour location, smoking status at first contact, pre-treatment tumour stage or pre-treatment standardised uptake value. Survival was poorer for patients who received the 50 Gy in 10 fractions schedule. Treatment was very well tolerated with very low rates of grade 3-4 toxicity (1%). CONCLUSIONS: SABR for peripherally located, medically inoperable non-small cell lung cancer can be safely and effectively implemented in a non-academic institution with appropriate equipment and training. Overall survival outcomes and toxicity rates are comparable with internationally published studies. Patients treated with 50 Gy in 10 fractions had a poorer survival outcome.

Stereotactic Body Radiotherapy Versus Delayed Surgery for Early-stage Non-small-cell Lung Cancer.

OBJECTIVE: To evaluate the overall survival of patients with operable stage IA non-small-cell lung cancer (NSCLC) who undergo "early" SBRT (within 0-30 days after diagnosis) versus "delayed" surgery (90-120 days after diagnosis). SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, national guidelines have recommended patients with operable stage IA NSCLC to consider delaying surgery by at least 3 months or, alternatively, to undergo SBRT without delay. It is unknown which strategy is associated with better short- and long-term outcomes. METHODS: Multivariable Cox proportional hazards modeling and propensity score-matched analysis was used to compare the overall survival of patients with stage IA NSCLC in the National Cancer Data Base from 2004 to 2015 who underwent "early" SBRT (0-30 days after diagnosis) versus that of patients who underwent "delayed" wedge resection (90-120 days after diagnosis). RESULTS: During the study period, 570 (55%) patients underwent early SBRT and 475 (45%) underwent delayed wedge resection. In multivariable analysis, delayed resection was associated with improved survival [adjusted hazard ratio 0.61; (95% confidence interval (CI): 0.50-0.76)]. Propensity-score matching was used to create 2 groups of 279 patients each who received early SBRT or delayed resection that were well-matched with regard to baseline characteristics. The 5-year survival associated with delayed resection was 53% (95% CI: 45%-61%) which was better than the 5-year survival associated with early SBRT (31% [95% CI: 24%-37%]). CONCLUSION: In this national analysis, for patients with stage IA NSCLC, extended delay of surgery was associated with improved survival when compared to early treatment with SBRT.

Modeling the Impact of Delaying the Diagnosis of Non-Small Cell Lung Cancer During COVID-19.

BACKGROUND: The novel coronavirus (COVID-19) pandemic has led surgical societies to recommend delaying diagnosis and treatment of suspected lung cancer for lesions less than 2 cm. Delaying diagnosis can lead to disease progression, but the impact of this delay on mortality is unknown. The COVID-19 infection rate at which immediate operative risk exceeds benefit is unknown. We sought to model immediate versus delayed surgical resection in a suspicious lung nodule less than 2 cm. METHODS: A decision analysis model was developed, and sensitivity analyses performed. The base case was a 65-year-old male smoker with chronic obstructive pulmonary disease presenting for surgical biopsy of a 1.5 to 2 cm lung nodule highly suspicious for cancer during the COVID-19 pandemic. We compared immediate surgical resection to delayed resection after 3 months. The likelihood of key outcomes was derived from the literature where available. The outcome was 5-year overall survival. RESULTS: Immediate surgical resection resulted in a similar but slightly higher 5-year overall survival when compared with delayed resection (0.77 versus 0.74) owing to the risk of disease progression. However, if the probability of acquired COVID-19 infection is greater than 13%, delayed resection is favorable (0.74 vs 0.73). CONCLUSIONS: Immediate surgical biopsy of lung nodules suspicious for cancer in hospitals with low COVID-19 prevalence likely results in improved 5-year survival. However, as the risk of perioperative COVID-19 infection increases above 13%, a delayed approach has similar or improved survival. This balance should be frequently reexamined at each health care facility throughout the curve of the pandemic.

Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2. METHODS: We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported. RESULTS: All patients were men with a mean age of 74.0 years (range 67-80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8-22); mean hospital stay was 33.8 days (range 21-60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively. CONCLUSIONS: Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.