A. Sasha Krupnick

Stereotactic body radiation therapy versus surgical resection for stage I non–small cell lung cancer

OBJECTIVES Stereotactic body radiation therapy has been proposed as an alternative local treatment option for high-risk patients with early-stage lung cancer. A direct comparison of outcomes between stereotactic body radiation therapy and surgical resection has not been reported. This study compares short-term outcomes between stereotactic body radiation therapy and surgical treatment of non-small cell lung cancer. METHODS We compared all patients treated with surgery (January 2000-December 2006) or stereotactic body radiation therapy (February 2004-May 2007) with clinical stage IA/B non-small cell lung cancer staged by computed tomography and positron emission tomography. Comorbidity scores were recorded prospectively using the Adult Co-Morbidity Evaluation scoring system. Charts were reviewed to determine local tumor recurrence, disease-specific survival, and overall survival. A propensity score matching analysis was used to adjust estimated treatment hazard ratios for confounding effects of patient age, comorbidity index, and clinical stage. RESULTS A total of 462 patients underwent surgery and 76 received stereotactic body radiation therapy. Overall, surgical patients were younger (P < .001), had lower comorbidity scores (P < .001), and better pulmonary function (forced expiratory volume in 1 second and carbon monoxide diffusion in the lung) (P < .001). Among the surgical and stereotactic body radiation therapy groups, 62.6% (291/462) and 78.9% (60/76) were in clinical stage IA, respectively. Final pathology upstaged 35% (161/462) of the surgery patients. In an unmatched comparison, overall 5-year survival was 55% with surgery, and the 3-year survival was 32% with radiation therapy. Among patients with clinical stage IA disease, 3-year local tumor control was 89% with radiation therapy and 96% with surgery (P = .04). There was no difference in local tumor control in stage IB disease (P = .89). No disease-specific survival differences were found in patients with 1A (P = .33) or IB disease (P = .69). Propensity analysis matched 57 high-risk surgical patients to 57 patients undergoing stereotactic body radiation therapy. In the matched comparison of this subgroup, there was no difference in freedom from local recurrence (88% vs 90%), disease-free survival (77% vs 86%), and overall survival (54% vs 38%) at 3 years. CONCLUSIONS In an unmatched comparison of clinical stage IA disease, surgical patients were healthier and had better local tumor control compared with those receiving stereotactic body radiation therapy. Propensity analysis in clinical stage IA/B non-small cell lung cancer revealed similar rates of local recurrence and disease-specific survival in patients treated with surgery compared with stereotactic body radiation therapy.

Lymph node evaluation in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

BACKGROUND With the emergence of video-assisted thoracic surgery (VATS) lobectomy, concern remains regarding the adequacy of nodal assessment versus thoracotomy. METHODS All clinical stage I non-small cell lung cancer patients treated with VATS or open lobectomy were retrospectively evaluated. Total nodes, N2 nodes, and nodes at each station were evaluated for associations with surgery type and location of involved lobe. RESULTS There were 79 VATS and 464 open lobectomy or segmental resections for stage I tumors. Overall, fewer lymph nodes were sampled with VATS compared with thoracotomy (7.4 +/- 0.6 vs 8.9 +/- 0.2, respectively; p = 0.029), and fewer N2 nodes were sampled with VATS versus thoracotomy as well (2.5 +/- 3.0 vs 3.7 +/- 3.3, p = 0.004). There were no differences in N1 node sampling between the two groups (5.2 +/- 3.6 vs 4.9 +/- 4.2, p = 0.592). Furthermore, there were more station 7 nodes with thoracotomy versus VATS (1.2 +/- 0.1 vs 0.6 +/- 0.1, p = 0.002). Among right-sided lesions, there was no difference in 4R nodes between groups (1.4 +/- 0.4 vs 1.6 +/- 0.2, p = 0.7) although there was a trend toward more level 7 nodes with thoracotomy (1.0 +/- 0.2 vs 1.4 +/- 0.2, p < 0.08). Among left-sided resections there were more station 7 nodes with thoracotomy versus VATS (1.0 +/- 0.1 vs 0.4 +/- 0.1, p < 0.001) and more station 5/6 nodes (1.1 +/- 0.1 vs 0.5 +/- 0.1, p < 0.04). For upper lobe resections, the total nodes (8.9 +/- 0.3 vs 7.4 +/- 0.7, p = 0.05) and station 7 nodes (1.0 +/- 0.1 vs 0.6 +/- 0.1, p < 0.01) were higher with thoracotomy than VATS. There was no difference in 2-year survival between groups (81% vs 83%, p = 0.4). CONCLUSIONS Our early experience with VATS has been associated with fewer lymph nodes sampled compared with open lobectomy although there was no survival difference. Analysis of these differences has directed us toward a more focused lymph node sampling with VATS lobectomy.

Endoscopic Ultrasound for Early Stage Esophageal Adenocarcinoma: Implications for Staging and Survival

BACKGROUND Patients often receive induction therapy based on endoscopic ultrasound (EUS)-identified nodal spread (N1) or deep tumor invasion (T3), although controversy exists regarding the role of induction therapy for early stage disease. We aim to evaluate the reliability of EUS in identifying early stage disease and the subsequent impact on treatment and outcomes. METHODS We retrospectively studied 149 patients who underwent EUS and esophagectomy for adenocarcinoma between January 2000 and December 2008. Computed tomography (CT) was performed in all patients, whereas positron emission tomography (PET) was performed in 91%. Clinical stage (c), pathologic stage (p), operative mortality, and survival were recorded. RESULTS Unanticipated pathologic nodal disease was similar in patients with cT1N0 and cT2N0 tumors (6/25 [24%] versus 7/18 [38.8%]; p=0.6). Among the 18 cases of cT2N0 disease, 9 (50%) were pathologically staged as T1N0, 8 (44%) were upstaged to pT3N0-1, and 1 (6%) was pT2N0. One case of cT1N0 tumor (4%) was upstaged to pT3N0. Among patients with cT1-2N0 tumors, 5-year disease-free survival for the group that was appropriately staged was 89.8% versus 39.9% for the group that had a higher pathologic stage than their clinical stage (ie, >T2N0) (p<0.001). Operative mortality for patients with cT1-2N0 tumors was 0/43 (0%), which was no different from that in the higher clinical stage groups with (1/37, 2.7%) or without (2/68, 2.9%) induction therapy (p=0.5). Multivariate analysis identified marked/intense uptake on staging PET (odds ratio, 5.76, 95%; confidence interval, 1.25 to 26.52; p=0.021) to be a factor predictive of upstaging of cT1-2N0 tumors. CONCLUSIONS Current staging techniques are inadequate for predicting T1-2N0 disease in esophageal adenocarcinoma. Survival is excellent with operation alone in patients with tumors appropriately staged as T1-2N0, although patients with tumors upstaged to greater than T2N0 have significantly worse survival. Other preoperative factors such as PET uptake may help select patients with cT1-2N0 tumors that will be upstaged at resection.

Treatment Outcomes in Stage I Lung Cancer: A Comparison of Surgery and Stereotactic Body Radiation Therapy

Introduction: The relative roles of surgery and stereotactic body radiation therapy in stage I non–small-cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Because there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Methods: Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared with those undergoing stereotactic body radiation therapy (SBRT) in exploratory unmatched and subsequent propensity matched analyses. Results: Between 1998 and 2010, 117,618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111,731 (95%) received surgery, whereas 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (versus T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596 of 109,485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 versus 33.3 months, p < 0.001) and matched analysis based on patient characteristics (62.3 versus 33.1 months, p < 0.001). Disease-specific survival was unavailable from the data set. Conclusion: In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control toward the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.

Unexpected readmission after lung cancer surgery: A benign event?

OBJECTIVE The study objective was to study the incidence, predictors, and implications of unanticipated early postoperative readmission after lung resection for non-small cell lung cancer. METHODS Patients undergoing surgery for clinical stage I to III non-small cell lung cancer were abstracted from the National Cancer Database. Regression models were fitted to identify predictors of 30-day readmission and to study the association of unplanned readmission with 30-day and long-term survival. RESULTS Between 1998 and 2010, 129,893 patients underwent resection for stage I to III non-small cell lung cancer. Of these, 5624 (4.3%) were unexpectedly readmitted within 30 days. In a multivariate regression model, increasing age, male gender, preoperative radiation, and pneumonectomy (odds ratio, 1.77; 95% confidence interval, 1.56-2.00) were associated with unexpected readmissions. Longer index hospitalization and higher Charlson comorbidity score were also predictive of readmission. The 30-day mortality for readmitted patients was higher (3.9% vs 2.8%), as was the 90-day mortality (7.0% vs 3.3%, both P < .001). In a multivariate Cox proportional hazards model of long-term survival, increasing age, higher Charlson comorbidity score, and higher pathologic stage (hazard ratio, for stage III 1.81; 95% confidence interval, 1.42-2.29) were associated with greater risk of mortality. Unplanned readmission was independently associated with a higher risk of long-term mortality (hazard ratio, 1.40; 95% confidence interval, 1.34-1.47). The median survival for readmitted patients was significantly shorter (38.7 vs 58.5 months, P < .001). CONCLUSIONS Unplanned readmissions are not rare after resection for non-small cell lung cancer. Such events are associated with a greater risk of short- and long-term mortality. With the renewed national focus on readmissions and potential financial disincentives, greater resource allocation is needed to identify patients at risk and develop measures to avoid the associated adverse outcomes.

Pathologic Upstaging in Patients Undergoing Resection for Stage I Non-Small Cell Lung Cancer: Are There Modifiable Predictors?

BACKGROUND A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. METHODS Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging. RESULTS From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n > 0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p < 0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p < 0.001) and were more likely to have positive resection margins (10% vs 2%, p < 0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01; >18 nodes OR 6.14). CONCLUSIONS Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease.

A Prospective Clinical Trial of Telecytopathology for Rapid Interpretation of Specimens Obtained During Endobronchial Ultrasound–Fine Needle Aspiration

BACKGROUND Cytopathologic interpretation of endobronchial ultrasound with fine needle aspiration (EBUS-FNA) samples by a pathologist can be time-consuming and costly, and an onsite cytopathologist may not always be readily available. A telecytopathology system was instituted and evaluated to examine the effect on operative time for EBUS. METHODS A prospective study was performed of sequential patients undergoing EBUS-FNA for the evaluation of mediastinal lymphadenopathy. Specimens for the control group were transported to the pathology laboratory, followed by remote cytologic interpretation. In a subsequent cohort, a telecytopathology system was used with intraoperative transmission of real-time live video microscopy to a remote cytopathologist (TCP group). The primary outcome was time to confirmation of cytology results. RESULTS Of 46 patients entered into the study, 23 underwent traditional analysis (control group), and 20 were analyzed using telecytopathology (TCP group). Lung cancer was the most common malignancy in both groups (12 TCP, 12 control). There was no difference in mean number of lymph node stations sampled (1.3 TCP vs 1.8 control, p = 0.76). Use of TCP was associated with fewer needle passes (4.9 vs 7.3, p = 0.02) and fewer slides for interpretation (8.4 vs 13.5, p = 0.01) per procedure. Time to result confirmation was significantly shorter in the TCP group (19.0 vs 46.7 minutes, p < 0.001). A diagnostic specimen was obtained in 70% of patients in the TCP group compared with 65% in the control group (p = 0.5). False-negative rates in patients undergoing EBUS-FNA and mediastinoscopy were similar between the two groups (0 in TCP vs 2 in control, p = 0.49). Mean procedural costs (excluding cost of the telecytology system and operating room time) were equivalent between the two groups (

National patterns of care and outcomes after combined modality therapy for stage IIIA non-small-cell lung cancer.

888 TCP vs

Adjuvant Therapy for Positive Nodes After Induction Therapy and Resection of Esophageal Cancer.

887 control). CONCLUSIONS Telecytopathology provides rapid interpretation of EBUS-FNA samples with diagnostic accuracy comparable to traditional methods, shortens procedure time, and is a more efficient model for delivery of on-site EBUS-FNA interpretation.

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Introduction: The role of surgery in addition to chemotherapy and radiation for stage IIIA non–small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery. Methods: Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence. Results: Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p < 0.001) and matched analysis based on patient characteristics (34.3 versus 18.4 months, p < 0.001). Conclusions: There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy seem to have better long-term survival.