Perioperative Lung Resection Outcomes After Implementation of a Multidisciplinary, Evidence-based Thoracic ERAS Program.

OBJECTIVE: This prospective study evaluated perioperative lung resection outcomes after implementation of a multidisciplinary, evidence-based Thoracic Enhanced Recovery After Surgery (ERAS) Program in an academic, quaternary-care center. BACKGROUND: ERAS programs have the potential to improve outcomes, but have not been widely utilized in thoracic surgery. METHODS: In all, 295 patients underwent elective lung resection for pulmonary malignancy from 2015 to 2019 PRE (n = 169) and POST (n = 126) implementation of an ERAS program containing all major ERAS Society guidelines. Propensity score-matched analysis, based upon patient, tumor, and surgical characteristics, was utilized to evaluate outcomes. RESULTS: After ERAS implementation, there was increased minimally invasive surgery (PRE 39.6%→POST 62.7%), reduced intensive care unit utilization (PRE 70.4%→POST 21.4%), improved chest tube (PRE 24.3%→POST 54.8%) and urinary catheter (PRE 20.1%→POST 65.1%) removal by postoperative day 1, and increased ambulation ≥3× on postoperative day 1 (PRE 46.8%→POST 54.8%). Propensity score-matched analysis that accounted for minimally invasive surgery demonstrated that program implementation reduced length of stay by 1.2 days [95% confidence interval (CI) 0.3-2.0; PRE 4.4→POST 3.2), morbidity by 12.0% (95% CI 1.6%-22.5%; PRE 32.0%→POST 20.0%), opioid use by 19 oral morphine equivalents daily (95% CI 1-36; PRE 101→POST 82), and the direct costs of surgery and hospitalization by $3500 (95% CI $1100-5900; PRE $23,000→POST $19,500). Despite expedited discharge, readmission remained unchanged (PRE 6.3%→POST 6.6%; P = 0.94). CONCLUSIONS: The Thoracic ERAS Program for lung resection reduced length of stay, morbidity, opioid use, and direct costs without change in readmission. This is the first external validation of the ERAS Society thoracic guidelines; adoption by other centers may show similar benefit.

Comparison of Conventional TNM and Novel TNMB Staging Systems for Non-Small Cell Lung Cancer.

Importance: Improved staging for non-small cell lung cancer (NSCLC) represents a critical unmet need. External validations of the eighth edition of the TNM staging system have yielded disappointing results, with persistently high mortality observed in early-stage disease. Objective: To determine whether incorporation of a molecular prognostic classifier into conventional TNM staging for NSCLC improves estimation of disease-free survival. Design, Setting, and Participants: This cohort study was conducted at an academic, quaternary care medical center from 2012 to 2018. A consecutive series of 238 patients underwent surgical resection of stage I to IIIC nonsquamous NSCLC and had molecular prognostic classifier testing performed. Data analysis was conducted in May 2019. Exposures: Patients were restaged according to the seventh and eighth editions of the TNM staging system and the novel TMMB staging system, which maintains the order and structure of the eighth edition of the TNM but downstages or upstages according to low or high molecular risk, respectively. Main Outcomes and Measures: The primary outcome was disease-free survival 3 years from the time of surgical resection. Reclassification statistics were then used to evaluate performance and improvement measures of the TNM seventh and eighth editions and the TNMB staging system. Results: Two hundred thirty-eight patients (144 [60.5%] female; median [interquartile range] age, 70 [63-75] years) were analyzed. The median (interquartile range) follow-up was 25 (14-40) months, and the disease-free survival rate was estimated to be 58.3% (95% CI, 45.7% to 69.0%). One hundred fifty-nine patients (66.8%) were reclassified by the TNMB staging system. Overall model fit remained the same for the seventh and eighth editions of the TNM staging system, whereas the R2 statistic (change from 0.22 to 0.31), concordance index (change from 0.68 to 0.73), and log-rank χ2 (change from 38 to 108) were all associated with improvements after TNMB adoption. The TNMB system, compared with the TNM eighth edition, was associated with enhanced identification of high-risk patients and better differentiation of those without recurrence from those who had recurrence (net reclassification improvement, 0.28; 95% CI, 0.08 to 0.46; P < .001), whereas the eighth edition compared with the seventh edition was not associated with improvement of this measure (net reclassification improvement, 0.02; 95% CI, -0.18 to 0.21; P = .87). Conclusions and Relevance: The TNMB staging system was associated with improved estimation of disease-free survival compared with conventional TNM staging. Incorporation of a molecular prognostic classifier into staging for NSCLC may lead to better identification of high-risk patients.

Current Molecularly Targeting Therapies in NSCLC and Melanoma.

Surgery, radiation therapy, and chemotherapy are the traditional options to control tumor progression. However, these strategies are fraught with harmful side effects and are ineffective in metastatic and advanced cancers. Biomarkers that are overexpressed in cancers and are involved in cell growth, proliferation, migration, and survival have recently become the focus of new molecular targeting therapies. Novel therapies targeting biomarkers have roles in tumorigenesis that are overexpressed in cancers may be more efficacious and less toxic in comparison to traditional therapies. These therapies include the use of tyrosine kinase inhibitors and monoclonal antibodies for the treatment of cancer. However, the efficacy of these therapies is limited due to the development of drug resistance after prolonged treatment. Current research is focused on understanding mechanisms of resistance to overcome the barriers limiting the use of these targeting therapies in the treatment of cancer. In this review, we will discuss the clinical status of tyrosine kinase inhibitors and monoclonal antibodies against several prevalent biomarkers that are candidates for therapy in non-small cell lung cancer (NSCLC) and melanoma.