Brian C. Gulack

Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer

PURPOSE Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer. PATIENTS AND METHODS Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis. RESULTS Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy. CONCLUSION Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.

Bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation

Over the last several decades, the growth of lung transplantation has been hindered by a much higher demand for donor lungs than can be supplied, leading to considerable waiting time and mortality among patients waiting for transplant. This has led to the search for an alternative bridging strategy in patients with end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation as well as a rescue strategy post-transplant for primary graft dysfunction (PGD) has been studied previously, however due to initially poor outcomes, its use was not heavily instituted. In recent years, with significant improvement in technologies, several single and multi-center studies have shown promising outcomes related to the use of ECMO as a bridging strategy as well as a therapy for patients suffering from PGD post-transplant. These results have challenged our current notion on ECMO use and hence forced us to reexamine the utility, efficacy and safety of ECMO in conjunction with lung transplantation. Through this review, we will address the various aspects related to ECMO use as a bridge to lung transplantation as well as a rescue post-transplant in the treatment of PGD. We will emphasize newer technologies related to ECMO use, examine recent observational studies and randomized trials of ECMO use before and after lung transplantation, and reflect upon our own institutional experience with the use of ECMO in these difficult clinical situations.

Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base

BACKGROUND Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated. METHODS Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching. RESULTS Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival. CONCLUSIONS In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short-term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques.

Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database

BACKGROUND This study was conducted to determine how malignant pleural mesothelioma (MPM) histology was associated with the use of surgery and survival. METHODS Overall survival of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the Surveillance, Epidemiology, and End Results database from 2004-2010 was evaluated using multivariate Cox proportional hazards models. RESULTS Of 1183 patients who met inclusion criteria, histologic subtype was epithelioid in 811 patients (69%), biphasic in 148 patients (12%), and sarcomatoid in 224 patients (19%). Median survival was 14 mo in the epithelioid group, 10 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). Cancer-directed surgery was used more often in patients with epithelioid (37%, 299/811) and biphasic (44%, 65/148) histologies as compared with patients with sarcomatoid histology (26%, 58/224; P < 0.01). Among patients who underwent surgery, median survival was 19 mo in the epithelioid group, 12 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). In multivariate analysis, surgery was associated with improved survival in the epithelioid group (hazard ratio [HR] 0.72; P < 0.01) but not in biphasic (HR 0.73; P = 0.19) or sarcomatoid (HR 0.79; P = 0.18) groups. CONCLUSIONS Cancer-directed surgery is associated with significantly improved survival for MPM patients with epithelioid histology, but patients with sarcomatoid and biphasic histologies have poor prognoses that may not be favored by operative treatment. The specific histology should be identified before treatment, so that surgery can be offered to patients with epithelioid histology, as these patients are most likely to benefit.

Long-term Oncologic Outcomes After Neoadjuvant Radiation Therapy for Retroperitoneal Sarcomas

OBJECTIVE To evaluate long-term survival among patients undergoing radiation therapy (RT), followed by surgical resection of retroperitoneal sarcomas (RPS). BACKGROUND Despite a lack of level 1 evidence supporting neoadjuvant RT for RPS, its use has increased substantially over the past decade. METHODS The 1998-2011 National Cancer Data Base was queried to identify patients who underwent resection of RPS. Subjects were grouped by use of neoadjuvant RT. Perioperative variables and outcomes were compared. Multivariable logistic regression was performed to assess predictors of neoadjuvant RT. Groups were propensity matched using a 2:1 nearest neighbor algorithm and short-term outcomes were compared. Finally, long-term survival was evaluated using the Kaplan-Meier method, with comparisons based on the log-rank test. RESULTS A total of 11,324 patients were identified. Neoadjuvant RT was administered to 696 patients (6.1%). During the study period, preoperative RT use increased from 4% to nearly 15%. Male sex, tumor size larger than 5 cm, treatment at an academic/research program, and higher tumor grade all predicted neoadjuvant RT administration. After propensity matching, the only difference in baseline characteristics was the use of neoadjuvant chemotherapy. Although neoadjuvant RT was associated with a higher rate of negative margins (77.5% vs 73.0%; P = 0.014), there was no corresponding improvement in 5-year survival (53.2% vs 54.2%; P = 0.695). CONCLUSIONS Despite the increasing use of neoadjuvant RT for patients with RPS, the survival benefit associated with this treatment modality remains unclear. Continued investigation is needed to better define the role of RT among patients with RPS.

Outcomes of Patients With Severe Chronic Lung Disease Who Are Undergoing Transcatheter Aortic Valve Replacement

BACKGROUND In this study, we sought to determine the clinical outcomes after transcatheter aortic valve replacement (TAVR) among patients with chronic lung disease (CLD) and to evaluate the safety of transaortic versus transapical alternate access approaches in patients with varying severities of CLD. METHODS Clinical records for patients undergoing TAVR from 2011 to 2014 in The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Medicare hospital claims (n = 11,656). Clinical outcomes were evaluated across strata of CLD severity, and the risk-adjusted association between access route and post-TAVR mortality was determined among patients with severe CLD. RESULTS In this cohort (median age, 84 years; 51.7% female), moderate to severe CLD was present in 27.7% (14.3%, moderate; 13.4%, severe). Compared with patients with no or mild CLD, patients with severe CLD had a higher rate of post-TAVR mortality to 1-year (32.3% versus 21.0%; adjusted hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.66), as did those with moderate CLD (25.5%; adjusted HR, 1.16; 95% CI, 1.03 to 1.30). The adjusted rate of mortality was similar for transapical versus transaortic approaches to 1 year (adjusted HR, 1.17; 95% CI, 0.83 to 1.65). CONCLUSIONS Moderate or severe CLD is associated with an increased risk of death to 1-year after TAVR, and among patients with severe CLD, the risk of death appears to be similar with either transapical or transaortic alternate-access approaches. Further study is necessary to understand strategies to mitigate risk associated with CLD and the long-term implications of these findings.

Value of surgical resection in children with high-risk neuroblastoma

The value of gross total resection (GTR) for children with high‐risk neuroblastoma (NB) is controversial. We hypothesized that patients undergoing GTR would demonstrate improved overall survival (OS) compared those having

The Utility of Preoperative Six-Minute-Walk Distance in Lung Transplantation.

RATIONALE The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. OBJECTIVES To evaluate the association between 6MWD and postoperative survival following lung transplantation. METHODS Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. MEASUREMENTS AND MAIN RESULTS A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. CONCLUSIONS 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.

Impact of donor and recipient hepatitis C status in lung transplantation

BACKGROUND Studies of lung transplantation in the setting of donors or recipients with hepatitis C virus (HCV) have been limited but have raised concerns about outcomes associated with this infection. METHODS Lung transplant cases in the United Network for Organ Sharing (UNOS) database from 1994 to 2011 were analyzed for the HCV status of both donor and recipient. First, among HCV-negative recipients, those who received a lung from an HCV-positive donor (HCV(+) D) were compared with those who received an HCV-negative lung (HCV(-) D). Donor, recipient and operative characteristics as well as outcomes were compared between groups, and overall survival was compared after adjustment for confounders. In a second analysis, HCV-positive recipients (HCV(+) R) were compared with HCV-negative recipients (HCV(-) R). The analysis was stratified by era (1994 to 1999 and 2000 to 2011) and long-term survival was compared. RESULTS Of 16,604 HCV-negative patients in the UNOS database, 28 (0.2%) received a lung from an HCV(+) D, with use of HCV(+) D decreasing significantly over time. Overall survival (OS) was shorter in the HCV(+) D group (median survival: 1.3 vs 5.1 years; p = 0.002). Results were confirmed in adjusted analyses. After inclusion criteria were met, 289 (1.7%) of the lung transplant recipients were HCV(+) R. These patients appeared similar to their HCV(-) R counterparts, except they were older and had more limited functional status. OS was significantly lower in HCV-positive individuals during the early era (median survival: 1.7 vs 4.5 years; p = 0.004), but not the recent era (median survival: 4.4 vs 5.4 years; p = 0.100). Again, results were confirmed by adjusted analysis. CONCLUSIONS HCV-positive status is a rare problem when considering both lung recipients and donors. Current data demonstrate significantly worse outcomes for HCV-negative patients receiving an HCV(+) lung; however, since 2000, HCV(+) recipients undergoing lung transplantation appear to have survival approximating that of HCV(-) recipients, an improvement from previous years. Recent medical advances in treatment for HCV may further improve outcomes in these groups.

Analysis of perioperative radiation therapy in the surgical treatment of primary and recurrent retroperitoneal sarcoma.

Radiation therapy (RT) is increasingly utilized in conjunction with surgery for the treatment of retroperitoneal soft tissue sarcomas (RPS). Despite multiple theoretical advantages of RT, its role in the surgical management of this disease remains ill defined.