Michelle C. Salazar

Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.

Importance Adjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non–small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient’s ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear. Objective To assess differences in survival according to the time interval between non–small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy. Design, Setting, and Participants This retrospective observational study examined treatment-naive patients with completely resected non–small-cell lung cancer who received postoperative multiagent chemotherapy between 18 and 127 days after resection between January 2004 and December 2012. The study population was limited to patients with lymph node metastases, tumors 4 cm or larger, or local extension. Patients were identified from the National Cancer Database, a hospital-based tumor registry that captures more than 70% of incident lung cancer cases in the United States. The association between time to initiation of adjuvant chemotherapy and survival was evaluated using Cox models with restricted cubic splines. Exposures Adjuvant chemotherapy administered at different time points after surgery. Main Outcomes and Measures Effectiveness of adjuvant chemotherapy according to time to initiation after surgery. Results A total of 12 473 patients (median [interquartile range] age, 64 [57-70] years) were identified: 3073 patients (25%) with stage I disease; 5981 patients (48%), stage II; and 3419 patients (27%), stage III. A Cox model with restricted cubic splines identified the lowest mortality risk when chemotherapy was started 50 days postoperatively (95% CI, 39-56 days). Initiation of chemotherapy after this interval (57-127 days; ie, the later cohort) did not increase mortality (hazard ratio [HR], 1.037; 95% CI, 0.972-1.105; P = .27). Furthermore, in a Cox model of 3976 propensity-matched pairs, patients who received chemotherapy during the later interval had a lower mortality risk than those treated with surgery only (HR, 0.664; 95% CI, 0.623-0.707; P < .001). Conclusions and Relevance In the National Cancer Database, adjuvant chemotherapy remained efficacious when started 7 to 18 weeks after non–small-cell lung cancer resection. Patients who recover slowly from non–small-cell lung cancer surgery may still benefit from delayed adjuvant chemotherapy started up to 4 months after surgery.

Length of Stay From the Hospital Perspective: Practice of Early Discharge Is Not Associated With Increased Readmission Risk After Lung Cancer Surgery.

Objective: To determine if hospitals that routinely discharge patients early after lobectomy have increased readmissions. Background: Hospitals are increasingly motivated to reduce length of stay (LOS) after lung cancer surgery, yet it is unclear if a routine of early discharge is associated with increased readmissions. The relationship between hospital discharge practices and readmission rates is therefore of tremendous clinical and financial importance. Methods: The National Cancer Database was queried for patients undergoing lobectomy for lung cancer from 2004 to 2013 at Commission on Cancer-accredited hospitals, which performed at least 25 lobectomies in a 2-year period. Facility discharge practices were characterized by a facilitys median LOS relative to the median LOS for all patients in that same time period. Results: In all, 59,734 patients met inclusion criteria; 2687 (4.5%) experienced an unplanned readmission. In a hierarchical logistic regression model, a routine of early discharge (defined as a facilitys tendency to discharge patients faster than the population median in the same time period) was not associated with increased risk of readmission (odds ratio 1.12, 95% confidence interval 0.97–1.28, P = 0.12). In a risk-adjusted hospital readmission rate analysis, hospitals that discharged patients early did not experience more readmissions (P = 0.39). The lack of effect of early discharge practices on readmission rates was observed for both minimally invasive and thoracotomy approaches. Conclusions: It is possible for hospitals to develop early discharge practices without increasing readmissions. Further study is needed to identify the critical practice elements that have enabled hospitals to aggressively discharge patients without increasing readmission risk.

Defining outcomes of patients with clinical stage I small cell lung cancer upstaged at surgery

BACKGROUND A proportion of patients with clinical stage I small cell lung cancer (SCLC) will be upstaged following surgical resection. The existing data regarding the management of upstaged SCLC patients and guidelines for their treatment remains sparse. The primary objective was to describe the impact of pathologic upstaging following surgical resection. METHODS The National Cancer Database was queried for patients with clinical stage I SCLC (cT1-2a,N0,M0) who underwent resection with curative intent followed by adjuvant therapy, excluding patients who underwent surgery alone. Clinical and pathologic T, N, and M staging were compared to identify patients that were upstaged. RESULTS Four-hundred and seventy-seven patients were identified with clinical stage I SCLC. Pathologic upstaging occurred in 25% (117). Of those upstaged, 30% (35) were due to a higher pathologic T descriptor and 81% (95) were due to the presence of nodal disease. Overall 5-year survival was significantly worse for upstaged patients compared with those patients who remained a pathologically stage I (36% vs 52%, p<0.001). Among patients with positive lymph node involvement, adjuvant chemotherapy and radiation therapy was associated a significantly improved 5-year survival compared to adjuvant chemotherapy alone (20% vs 55%, respectively, p<0.01). The use of adjuvant chemotherapy and radiation therapy in patients with nodal disease after surgical resection was an independent predictor of improved survival (HR 0.36, 95% CI 0.18-0.73, p<0.01). CONCLUSIONS Pathologic upstaging is common after surgical resection of stage I SCLC, and is associated with significantly inferior survival. These data provide evidence that recommend the use of adjuvant chemotherapy and radiation therapy in the setting of nodal upstaging after resection of clinical stage I SCLC patients.

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival

Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting. Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence. Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non–small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1–expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45−) and cytokeratin negative (CK−, PD-L1+, CD45−) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64–9.09; P = 0.002). Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival. Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139–45. ©2017 AACR.

Lung Cancer in the Very Young: Treatment and Survival in the National Cancer Data Base

Introduction: Young patients with lung cancer represent a distinct subset of patients with this disease. The National Cancer Data Base includes patients of all ages and contains detailed staging, treatment, and survival information. The objective of this study was to examine treatment patterns and outcomes in young patients with non–small cell lung cancer (NSCLC). Methods: The National Cancer Data Base was queried for NSCLC cases from 2003 to 2009. Younger patients were defined as those aged 20 to 46 years. Older patients were defined as those aged 47 to 89 years. Patient demographics, tumor characteristics, treatment, and survival were analyzed. The primary outcomes were 5‐year overall and relative survival. Results: The study included 173,856 patients; 5657 were 20 to 46 years of age. Younger patients were treated differently and received more aggressive therapy at each stage. At stage I, 64% of younger patients received surgery only versus 55% of the older patients (p < 0.0001). Younger patients had improved survival at all stages. This effect was more pronounced at earlier stages (the hazard ratios for the older group were 1.84, 1.62, 1.18, and 1.14 for stages I through IV, respectively [all p < 0.0001]). The absolute differences in 5‐year overall survival between the younger and older groups were 25% for stages I and II but only 9% and 2% for stages III and IV, respectively. Conclusions: Overall and relative survival in younger patients with NSCLC is better than in older patients, with greater benefit seen in earlier stages. Despite having fewer comorbidities and undergoing more aggressive treatment, younger patients with advanced‐stage NSCLC have only marginally better overall and relative survival than older patients.

Adjuvant Chemotherapy for T3 Non–Small Cell Lung Cancer with Additional Tumor Nodules in the Same Lobe

Introduction: Adjuvant chemotherapy after surgical resection of non–small cell lung cancer is associated with a survival advantage in several staging scenarios. T3 tumors associated with a separate tumor nodule in the same lobe (formerly “satellite nodules”) have a significant risk for systemic failure, yet the efficacy of adjuvant chemotherapy in this setting is unknown. The survival of patients with T3 tumors and additional tumor nodules in the same lobe treated with and without postoperative chemotherapy was evaluated to understand the role of adjuvant chemotherapy in this setting. Methods: The National Cancer Data Base was queried for patients with T3 tumors with additional tumor nodules in the same lobe between 2010 and 2012. Primary outcomes were 3‐year overall and relative survival (a surrogate of cancer‐specific survival). Results: A total of 1013 patients with T3 tumors and additional tumor nodules in the same lobe were identified; 56% received multiagent postoperative chemotherapy and 44% were treated with surgical resection only. The use of adjuvant chemotherapy versus resection alone was associated with improved 3‐year overall survival (70% versus 59%, p < 0.001). A Cox model adjusting for patient, tumor, and treatment factors demonstrated that adjuvant chemotherapy was associated with a survival advantage compared with resection alone (hazard ratio = 0.544, p < 0.0001). Relative 3‐year survival was also improved in the adjuvant chemotherapy subgroup (74% versus 64% for the surgery‐only subgroup). Conclusions: Adjuvant chemotherapy is associated with increased overall survival among patients with T3 tumors with additional pulmonary nodules. Further study is warranted to clarify the role of adjuvant chemotherapy in this setting.

Effectiveness of local therapy for stage I non–small-cell lung cancer in nonagenarians

Background: Stage I non–small‐cell lung cancer is potentially curable, yet older patients undergo treatment at lower rates than younger patients. This analysis sought to describe the treatment outcomes of nonagenarians with stage I non–small‐cell lung cancer to better guide treatment decisions in this population. Methods: The National Cancer DataBase was queried for patients age ≥90 years old with stage I non–small‐cell lung cancer (tumors ≤4 cm). Patients were divided into 3 groups: local therapy, other therapy, or no treatment. The primary outcomes were 5‐year overall and relative survival. Results: Of the 616 patients identified, 33% (202) were treated with local therapy, 34% (207) were treated with other therapy, and 34% (207) underwent no treatment. Compared with local therapy, overall mortality was significantly higher with no treatment (hazard ratio 2.50, 95% confidence interval, 1.95–3.21) and other therapy (hazard ratio 1.43, 95% confidence interval, 1.11–1.83). The 5‐year relative survival was 81% for local therapy, 49% for other therapy, and 32% for no treatment (P < .0001). Conclusion: Nonagenarians managed with local therapy for stage I non–small‐cell lung cancer (tumors ≤4 cm) have better overall survival than those receiving other therapy or no treatment and should be considered for treatment with either operation or stereotactic body radiation therapy if able to tolerate treatment.

Validating the Thoracic Revised Cardiac Risk Index Following Lung Resection

BACKGROUND The Thoracic Revised Cardiac Index (ThRCRI) is a tool that differentiates patients who may proceed to lung resection (classes A or B) from those who should receive additional cardiac evaluation (classes C or D). This study aims to describe the ability of the ThRCRI to stratify patients based on major cardiac complication rates using a large multi-institutional dataset. METHODS Patients undergoing lobectomy or pneumonectomy were identified in the American College of Surgeons National Surgical Quality Improvement Program dataset from 2005 to 2012. Patients were grouped into 4 risk classes based on a summary score of preoperative risk factors: ischemic heart disease, cerebrovascular disease, renal comorbidity, and pneumonectomy. The primary outcome was the incidence of perioperative major cardiac complication in each of the 4 risk classes. RESULTS Of the 4,625 patients identified, the majority underwent surgery for malignant disease (78%) and had an open procedure (70%). Among ThRCRI risk factors, 9% of patients had ischemic heart disease, 7% had cerebrovascular disease, 2% had renal comorbidity, and 6% underwent pneumonectomy. Incidence of cardiac complication in all patients was 2%. Incidence of cardiac complication within risk classes A, B, C, and D were 1%, 3%, 9%, and 4%, respectively (p < 0.01). CONCLUSIONS Using a large multi-institutional dataset, the ThRCRI can differentiate patients at higher risk for cardiac complication following lung resection (classes C and D) and can be a useful preoperative instrument. The ThRCRI may allow for identifying patients who would benefit from additional cardiac evaluation.