JTO Clinical and Research Reports最新文献

Introduction

Methods

Results

Conclusions

Introduction

Methods

Results

Conclusions

Introduction

Methods

Results

Conclusions

Introduction

Early lung cancer detection programs improve surgical resection rates and survival but may skew toward more indolent cancers.

Methods

Hypothesizing that differences in stage-stratified survival indicate differences in biological aggressiveness and possible length-time and overdiagnosis bias, we assessed a cohort who had curative-intent resection, categorized by diagnostic pathways: screening, incidental pulmonary nodule program, and non–program based. Survival was analyzed using Kaplan-Meier plots, log-rank tests, and Cox regression, comparing aggregate and stage-stratified survival across cohorts with Tukey’s method for multiple testing.

Results

Of 1588 patients, 111 patients (7%), 357 patients (22.5%), and 1120 patients (70.5%) were diagnosed through screening, pulmonary nodule, and non–program-based pathways; 0% versus 9% versus 6% were older than 80 years (p = 0.0048); 17%, 23%, and 24% had a Charlson Comorbidity score greater than or equal to 2 (p = 0.0143); 7%, 6%, and 9% had lepidic adenocarcinoma; 26%, 31%, and 34% had poorly or undifferentiated tumors (p = 0.1544); and 93%, 87%, and 77% had clinical stage I (p < 0.0001).

Aggregate 5-year survival was 87%, 72%, and 65% (p = 0.0009), including 95%, 74%, and 74% for pathologic stage I. Adjusted pairwise comparisons showed similar survival in screening and nodule program cohorts (p = 0.9905). Nevertheless, differences were significant between screening and non–program-based cohorts (p = 0.0007, adjusted hazard ratio 0.33 [95% confidence interval: 0.18–0.6]) and between nodule and nonprogram cohorts (adjusted hazard ratio 0.77 [95% confidence interval: 0.61–0.99]). Stage I comparisons yielded p = 0.2256, 0.1131, and 0.911. In respective pathways, 0%, 2%, and 2% of patients with stage I disease who were older than 80 years had a Charlson score greater than or equal to 2 (p = 0.3849).

Conclusions

Neither length-time nor overdiagnosis bias was evident in NSCLC diagnosed through screening or incidental pulmonary nodule programs.

Introduction

Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice.

Methods

A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020.

Results

A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38).

Conclusions

During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.

Introduction

Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors.

Methods

Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively.

Results

Overall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of <5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, p = 0.029 and odds ratio = 1.90, p = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, p < 0.001 and hazard ratio = 4.99, p < 0.001, respectively).

Conclusions

Within patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.

Introduction

Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).

Methods

We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.

Results

A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.

Conclusions

Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.

Non-small cell lung cancer recurrence after curative-intent surgery remains a challenge despite advancements in treatment. We review postoperative surveillance strategies and their impact on overall survival, highlighting recommendations from clinical guidelines and controversies. Studies suggest no clear benefit from more intensive imaging, whereas computed tomography scans reveal promise in detecting recurrence. For early-stage disease, including ground-glass opacities and adenocarcinoma in situ or minimally invasive adenocarcinoma, less frequent surveillance may suffice owing to favorable prognosis. Liquid biopsy, especially circulating tumor deoxyribonucleic acid, holds potential for detecting minimal residual disease. Clinicopathologic factors and genomic profiles can also provide information about site-specific metastases. Machine learning may enable personalized surveillance plans on the basis of multi-omics data. Although precision medicine transforms non-small cell lung cancer treatment, optimizing surveillance strategies remains essential. Tailored surveillance strategies and emerging technologies may enhance early detection and improve patients’ survival, necessitating further research for evidence-based protocols.

Introduction

ALK–rearranged advanced NSCLC (aNSCLC) represents 4% of all NSCLCs, and multiple ALK-targeted therapies (ALK-inhibitors) are now available for use. Little is known about changes in treatment patterns, or how prognostic factors and sequence of therapy may impact overall survival in the real-world setting. We aim to describe initial and subsequent treatments used, survival outcomes, prognostic factors, and the impact of treatment on overall survival in the largest (N = 739) real-world cohort of patients with ALK+ aNSCLC reported in the literature.

Methods

Retrospective observational cohort study with data drawn from a U.S.-based electronic health record–derived, deidentified database. Eligible patients were diagnosed with ALK+ aNSCLC between 2011-2020 and were treated in multiple different cancer clinics and across multiple geographic regions throughout the United States.

Results

From a cohort of 63,667 patients with aNSCLC, 739 patients with ALK+ NSCLC were eligible for analysis, median age was 63 years, 54% patients were female, and 85% were managed in community setting. More than 168 different treatment sequences were observed, and treatment utilization changed over time. Cohort median overall survival was 37 months (95% confidence interval: 33–45). Positive prognostic factors were as follows: never-smoking history, younger age, treatment in an academic setting, and initial early stage at diagnosis. Initial treatment with a second-generation ALK-inhibitor was associated with improved survival compared with chemotherapy.

Conclusions

For people with ALK+ aNSCLC, this study has identified several important clinical prognostic factors and is practice affirming; first-line treatment with a second-generation ALK-inhibitor improves survival compared with chemotherapy.

Introduction

Lung cancer screening (LCS) reduces lung cancer mortality, yet uptake pre– and post–coronavirus disease 2019 (COVID-19) remains low. The impact of COVID-19 on LCS programs across the United States is unknown. Ours is the first multi-institutional study to identify barriers to LCS experienced during the pandemic. Our work will hopefully inform the development of targeted resources to facilitate increased uptake of LCS.

Methods

A nationwide survey of Centers of Excellence (SCOE) in LCS was conducted by GO2 for Lung Cancer Foundation. In 2021, survey items included questions regarding program structure, screening rates, and systemic barriers to LCS delivery experienced amid COVID-19.

Results

A total of 99 programs representing 1112 screening sites responded. A median of 868 patients were screened during the year of 2020. Patient recruitment, patient education, and in-person service access were negatively affected by COVID-19, whereas the use of telemedicine was positively affected. Coordination of care and timely reporting of results were largely unaffected by the pandemic.

Conclusions

Our findings provide a real-world snapshot of how COVID-19 affected LCS from a program perspective. These findings highlight ongoing challenges with educating and engaging those at high risk for lung cancer in LCS. Program resources should be directed toward increasing adherence to LCS among eligible patients.