Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery.

INTRODUCTION: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). METHODS: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. RESULTS: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). CONCLUSIONS: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer.

BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

Experience With Medical Marijuana for Cancer Patients in the Palliative Setting.

OBJECTIVES: Medical marijuana is a symptom treatment option for palliative cancer patients; however, its useful applications remain limited. The goals of this study were to review the characteristics of patients who received medical marijuana under our ambulatory palliative care program and to determine barriers to access and use of medical marijuana in this population. METHODS: This study was a retrospective analysis of patients who were enrolled in the medical marijuana registry through the ambulatory palliative care department at Upstate Cancer Center. Data from June 2017 to June 2020 were analyzed. Patients were included if they had a diagnosis of cancer, were certified by a qualified practitioner in the New York Medical Marijuana Program, and received care at Upstate Medical University. Patients were excluded if no marijuana certificate was found or if they transferred care. RESULTS: The study population was 184 patients. Ninety-three patients (51.5%) received at least one prescription from a New York licensed marijuana dispensary while 72 (39.13%) were certified but never obtained any medical marijuana. For patients who took at least one dose of medical marijuana, 48.14% experienced an improvement in pain, 44.95% used fewer opioids, and 85.11% had an improvement in at least one symptom. Adverse effects were low at 3.72%. CONCLUSION: Medical marijuana has an important role in the palliation of symptoms in advanced cancers with few adverse effects. There are still many barriers to effective use. More prospective research is needed to optimize delivery and dosing.

Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503).

BACKGROUND: Increased detection of small-sized, peripheral, non-small-cell lung cancer has renewed interest in sublobar resection instead of lobectomy, the traditional standard of care for early-stage lung cancer. We aimed to assess morbidity and mortality associated with lobar and sublobar resection for early-stage lung cancer. METHODS: CALGB/Alliance 140503 is a multicentre, international, non-inferiority, phase 3 trial in patients with peripheral non-small-cell lung cancer clinically staged as T1aN0. Patients were recruited from 69 academic and community-based institutions in Australia, Canada, and the USA. Patients were randomly assigned intraoperatively to either lobar or sublobar resection. The random assignment was based on permuted block randomisation without concealment and was stratified according to radiographic tumour size, histology, and smoking status. The primary endpoint of the trial is disease-free survival; here, we report a post-hoc, exploratory, comparative analysis of perioperative mortality and morbidity associated with lobar and sublobar resection. Perioperative mortality was defined as death from any cause within 30 days and 90 days of surgical intervention and was calculated for all randomised patients. Morbidity was graded using Common Terminology Criteria for Adverse Events version 4.0. All analyses were done on an intention-to-treat basis for randomised patients with data available. This trial is registered with ClinicalTrials.gov, number NCT00499330. FINDINGS: Between June 15, 2007, and March 13, 2017, 697 patients were randomly allocated to either lobar resection (n=357) or sublobar resection (n=340; 59% wedge resection). Six (0·9%) patients died by 30 days, four (1·1%) after lobar resection and two (0·6%) after sublobar resection; by 90 days, ten (1·4%) patients had died, six (1·7%) after lobar resection and four (1·2%) after sublobar resection (difference at 30 days, 0·5%, 95% CI -1·1 to 2·3; difference at 90 days, 0·5%, 95% CI -1·5 to 2·6). An adverse event of any grade occurred in 193 (54%) of 355 patients after lobar resection and 172 (51%) of 337 patients after sublobar resection. Adverse events of grade 3 or worse occurred in 54 (15%) patients assigned lobar resection and in 48 (14%) patients assigned sublobar resection. No differences between surgical approaches were noted in cardiac or pulmonary complications. Grade 3 haemorrhage (requiring transfusion) occurred in six (2%) patients assigned lobar resection and eight (2%) patients assigned sublobar resection. Prolonged air leak occurred in nine (3%) patients after lobar resection and two (1%) patients after sublobar resection. INTERPRETATION: Our post-hoc analysis showed that perioperative mortality and morbidity did not seem to differ between lobar and sublobar resection in physically and functionally fit patients with clinical T1aN0 non-small-cell lung cancer. These data may affect the daily choices made by patients and their doctors in establishing the best treatment approach for stage I lung cancer. FUNDING: National Cancer Institute.

Impact of ASA score misclassification on NSQIP predicted mortality: a retrospective analysis.

BACKGROUND: The ASA physical classification score has a major impact on the observed/expected (O/E) mortality ratio in the NSQIP General Vascular Mortality Model. The difference in predicted mortality is greatest between ASAs 3 and 4. We hypothesized under-classified ASA scores significantly affect the O/E mortality. METHODS: We conducted a retrospective review of NSQIP essential surgery cases from January 2014 to December 2014 (n = 1264) with mortality sub-analysis (n = 33) at our institution. We recorded transfer and emergency status and independently calculated the ASA score for mortalities using published definitions. A random sample of 50 survivors and 10 emergency survivors were reviewed and ASA recalculated. We performed statistical modeling to simulate the effects of ASA misclassifications. Statistical analysis was performed using JMP 10 and SAS 9.4. RESULTS: ASA was under-classified in 18.2% of mortalities, most commonly ASAs 3 and 4. Sixteen percent of ASA 3 survivors were misclassified, including 60% in the emergency subgroup (p < 0.05 vs. elective cases). Patients transferred from other institutions were more likely to be emergency cases than non-transferred patients (43.5 vs. 7.84%, p < 0.05). Transferred patients had a higher proportion of ASAs 3-5 vs. ASAs 1-2 compared with non-transfers (84.38 vs. 49.76%, p < 0.05) Simulation data showed ASA misclassification underestimated predicted mortality by 2.5 deaths on average. CONCLUSION: ASA misclassification significantly impacts O/E mortality. With accurate ASA classification, observed mortality would not have exceeded expected mortality in our institution. Education regarding the impact of ASA scoring is critical to ensure accurate O/E mortality data at hospitals using NSQIP to assess surgical quality.

Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503.

OBJECTIVE: Cancer and Leukemia Group B 140503 is an ongoing, multicenter randomized trial assessing whether sublobar resection is equivalent to lobectomy for the treatment of stage I A non-small cell lung cancer (NSCLC) ≤2 cm in diameter. The objective of this report is to determine the reasons precluding intraoperative randomization. METHODS: From June 15, 2007, to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty-nine were randomized successfully (61%), and 248 patients were not randomized (39%). We analyzed the reasons for nonrandomization among a subset of the nonrandomized patients (208) for whom additional data were available. RESULTS: Of these 208 patients, undiagnosed benign nodules (n =104, 16% of all registered patients) and understaging of NSCLC (n =45, 7% of all registered patients) were the dominant reasons precluding randomization. Granulomas represent one-quarter of the benign nodules. The understaged patients had unsuspected nodal metastases (n =28) or other more advanced NSCLC. The rate of randomization was significantly greater in those patients who had a preoperative biopsy (P <.001). CONCLUSIONS: In a carefully monitored cohort of patients with suspected small NSCLC ≤2 cm, a substantial number are misdiagnosed (benign nodules) or understaged. These patients may not have benefited from a thoracic surgical procedure. Preoperative biopsy significantly increased the rate of correct diagnosis. Preoperative biopsy of small suspected NSCLC will reduce the number of nontherapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.

Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules.

OBJECTIVE: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014. BACKGROUND: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules. METHODS: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates. RESULTS: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8), centrally located tumor (HR 2.5, 95% CI 1.2-5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2-6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4-6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24). CONCLUSIONS: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.

Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance).

PURPOSE: Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. MATERIALS AND METHODS: Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. RESULTS: Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. CONCLUSION: NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.

VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance).

BACKGROUND: The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. METHODS: Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar's test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. RESULTS: The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. CONCLUSIONS: This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

OBJECTIVES: A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. METHODS: We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. RESULTS: Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). CONCLUSIONS: Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer.

Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer.

OBJECTIVE: Surgical management is a critical component of computed tomography (CT) screening for lung cancer. We report the results for US sites in a large ongoing screening program, the International Early Lung Cancer Action Program (I-ELCAP). METHODS: We identified all patients who underwent surgical resection. We compared the results before (1993-2005) and after (2006-2011) termination of the National Lung Screening Trial to identify emerging trends. RESULTS: Among 31,646 baseline and 37,861 annual repeat CT screenings, 492 patients underwent surgical resection; 437 (89%) were diagnosed with lung cancer; 396 (91%) had clinical stage I disease. In the 54 (11%) patients with nonmalignant disease, resection was sublobar in 48 and lobectomy in 6. The estimated cure rate based on the 15-year Kaplan-Meier survival for all 428 patients (excluding 9 typical carcinoids) with lung cancer was 84% (95% confidence interval [CI], 80%-88%) and 88% (95% CI, 83%-92%) for clinical stage I disease resected within 1 month of diagnosis. Video-assisted thoracoscopic surgery and sublobar resection increased significantly, from 10% to 34% (P < .0001) and 22% to 34% (P = .01) respectively; there were no significant differences in the percentage of malignant diagnoses (90% vs 87%, P = .36), clinical stage I (92% vs 89%, P = .33), pathologic stage I (85% vs 82%, P = .44), tumor size (P = .61), or cell type (P = .81). CONCLUSIONS: The frequency and extent of surgery for nonmalignant disease can be minimized in a CT screening program and provide a high cure rate for those diagnosed with lung cancer and undergoing surgical resection.

Comparison of performance status with peak oxygen consumption in operable patients with non-small-cell lung cancer.

BACKGROUND AND OBJECTIVE: In this era of increasing options for treatment of 'surgical' lung cancer patients, preoperative physiologic assessment of accurate patient selection is becoming more important. The variability in an objective measure of cardiorespiratory fitness (peak oxygen consumption (VO2peak )) across performance in operable non-small-cell lung cancer (NSCLC) patients enrolled in the Cancer and Leukemia Group B trial was compared. METHODS: Using a cross-sectional design, 392 NSCLC patients underwent an incremental cardiopulmonary cycling exercise test to symptom limitation with expired gas analysis to determine VO2peak . Performance status (PS) was assessed using the Eastern Cooperative Oncology Group (ECOG) tool. RESULTS: There was a significant decrease in VO2peak across increasing ECOG categories (P < 0.0001). However, there was a large range in VO2peak for any given ECOG category with overlap between categories (ECOG 0: 5.0-31.5 mL/kg/min; ECOG 1: 4.3-24.8 mL/kg/min; ECOG 2: 8.9-21.9 mL/kg/min; ECOG 3; 3.3-11.7 mL/kg/min). CONCLUSIONS: PS scoring systems do not provide a sensitive measure of functional status. Objective measures such as VO2peak may be a useful in the clinical management of oncology patients.

Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803.

OBJECTIVE: Accurate pathologic restaging of N2 stations after neoadjuvant therapy in stage IIIA (N2) non-small cell lung cancer is needed. METHODS: A prospective multi-institutional trial was designed to judge the feasibility of videothoracoscopy to restage the ipsilateral nodes in mediastinoscopy-proven stage IIIA (N2) non-small cell lung cancer after 2 cycles of platinum-based chemotherapy and/or 40 Gy or more of radiotherapy. The goals included biopsy of 3 negative N2 node stations or to identify 1 positive N2 node or pleural carcinomatosis. RESULTS: Ten institutions accrued 68 subjects. Of the 68 subjects, 46 (68%) underwent radiotherapy and 66 (97%) underwent chemotherapy. Videothoracoscopy successfully met the prestudy feasibility in 27 patients (40%): 3 negative stations confirmed at thoracotomy in 7, persistent stage N2 disease in 16, and pleural carcinomatosis in 4. In 20 procedures (29%), no N2 disease was found, 3 stations were not biopsied because of unanticipated nodal obliteration. Thus, 47 videothoracoscopy procedures (69%, 95% confidence interval, 57%-80%) restaged the mediastinum. Videothoracoscopy was unsuccessful in 21 patients (31%) because the procedure had to be aborted (n = 11) or because of false-negative stations (n = 10). Of the 21 failures, 15 were right-sided, and 10 had a positive 4R node. The sensitivity of videothoracoscopy was 67% (95% confidence interval, 47%-83%), and the negative predictive value was 73% (95% confidence interval, 56%-86%) if patients with obliterated nodal tissue were included. The sensitivity was 83% (95% confidence interval, 63%-95%) and the negative predictive value was 64% (95% confidence interval, 31%-89%) if those patients were excluded. The specificity was 100%. One death occurred after thoracotomy. CONCLUSIONS: Videothoracoscopy restaging was "feasible" in this prospective multi-institutional trial and provided pathologic specimens of the ipsilateral nodes. Videothoracoscopy restaging was limited by radiation and the 4R nodal station.

Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: results from Cancer and Leukemia Group B 159902.

OBJECTIVE: Previous studies suggest that cytologic analysis of cells obtained by lavage of the pleural surfaces at the time of resection of non-small cell lung cancer can identify patients at risk for recurrence. Because telomerase gene expression has been associated with worse outcome in non-small cell lung cancer, we hypothesized that identification of cells obtained from pleural lavage that express telomerase would identify patients at risk for recurrent disease. METHODS: Patients with presumed non-small cell lung cancer underwent thoracotomy with curative intent. Cells obtained by lavage of the pleural surfaces were analyzed for telomerase catalytic subunit human telomerase reverse transcriptase mRNA expression using reverse transcriptase polymerase chain reaction. RESULTS: A total of 194 patients with stage I/II non-small cell lung cancer had adequate samples, and median follow-up was 60 months (17-91 months). By using Cox models, no statistical differences were found between human telomerase reverse transcriptase-negative and positive patients in disease-free survival (hazard ratio, 1.28; 95% confidence interval, 0.85-1.94; log-rank test, P = .2349) or overall survival (hazard ratio, 1.13; 95% confidence interval, 0.72-1.79; log-rank test, P = .5912) CONCLUSIONS: Detection of human telomerase reverse transcriptase in cells obtained from pleural lavage of patients with stage I/II non-small cell lung cancer does not identify patients at risk for recurrent disease.

Optimal management of malignant pleural effusions (results of CALGB 30102).

The optimal strategy to achieve palliation of malignant pleural effusions (MPEs) is unknown. This multi-institutional, prospective, randomized trial compares 2 established methods for controlling symptomatic unilateral MPEs. Patients with unilateral MPEs were randomized to either daily tunneled catheter drainage (TCD) or bedside talc pleurodesis (TP). This trial is patterned after a previous randomized trial that showed that bedside TP was equivalent to thoracoscopic TP (CALGB 9334). The primary end point of the current study was combined success: consistent/reliable drainage/pleurodesis, lung expansion, and 30-day survival. A secondary end point, survival with effusion control, was added retrospectively. This trial randomized 57 patients who were similar in terms of age (62 years), active chemotherapy (28%), and histologic diagnosis (lung, 63%; breast, 12%; other/unknown cancers, 25%) to either bedside TP or TCD. Combined success was higher with TCD (62%) than with TP (46%; odds ratio, 5.0; P = .064). Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores (8.7 vs. 5.9; P = .036), especially in the subgroup with impaired expansion (9.1 vs. 4.6; P = .042). Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP (82% vs. 52%, respectively; P = .024). In this prospective randomized trial, TCD achieved superior palliation of unilateral MPEs than TP, particularly in patients with trapped lungs.

Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer.

BACKGROUND: Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with nonsmall cell lung cancer (NSCLC). The authors investigated the prognostic significance of preoperative cardiorespiratory fitness (peak oxygen consumption [VO(2peak)]) among operable candidates with NSCLC. METHODS: By using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO(2peak) and were observed until death or June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO(2peak) tertiles (<0.96 of 0.96-1.29/>1.29 L/min⁻¹) with adjustment for age, sex, and performance status. RESULTS: Median follow-up was 30.8 months; 294 deaths were reported during this period. Compared with patients achieving a VO(2peak) <0.96 L/min⁻¹, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% confidence interval [CI], 0.46-0.88) for a VO(2peak) of 0.96 to 1.29 L/min⁻¹, and 0.56 (95% CI, 0.39-0.80) for a VO(2peak) of >1.29 L/min⁻¹) (P(trend) = .0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46-0.95) and 0.59 (95% CI, 0.40-0.89) relative to the lowest VO(2peak) category (P(trend) = .0247), respectively. For nonresected patients, the HRs were 0.78 (95% CI, 0.34-1.79) and 0.39 (95% CI, 0.16-0.94) relative to the lowest category (P(trend) = .0278). CONCLUSIONS: VO(2peak) is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.

Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial.

INTRODUCTION: Sentinel node mapping with radioactive technetium in non-small cell lung cancer has been shown to be feasible in several single institution reports. The Cancer and Leukemia Group B designed a phase II trial to test a standardized method of this technique in a multi-institutional setting. If validated, the technique could provide a more accurate and sensitive way to identify lymph node metastases. METHODS: Patients with clinical stage I non-small cell lung cancer amenable to resection were candidates for this trial. Intraoperatively, tumors were injected with technetium sulfur colloid (0.25 mCi). The tumor and lymph nodes were measured in vivo with a hand held Geiger counter and resection of the tumor and nodes was carried out. Sentinel nodes, all other nodes and the tumor were analyzed with standard histologic assessment. Negative sentinel nodes were also evaluated with immunohistochemistry. RESULTS: In this phase II trial, 8 surgeons participated (1-13 patients enrolled per surgeon), and 46 patients (out of a planned 150) were enrolled. Of these, 43 patients had cancer and an attempted complete resection, and 39 patients underwent sentinel node mapping. One or more sentinel nodes were identified in 24 of the 39 patients (61.5%). The sentinel node(s) were found to be accurate (no other nodes were positive for cancer if the sentinel node was negative) in 20/24 patients (83.3%). In the overall group the sentinel node mapping procedure was found to be accurate in 20/39 patients (51.2%). CONCLUSIONS: Intraoperative sentinel node mapping in lung cancer with radioisotope yielded lower accrual and worse accuracy than expected. The multi-institutional attempt at validating this technique was unsuccessful.

Definitive treatment of poor-risk patients with stage I lung cancer: a single institution experience.

PURPOSE: Lung cancer remains the leading cause of cancer death in both men and women. A substantial number of patients with early stage non-small cell lung cancer (NSCLC) are unfit for standard surgery due to cardiopulmonary dysfunction and/or other comorbidity. The appropriate management for this population has not been defined. METHODS: Retrospective analysis of patients with clinical stage I NSCLC judged to be unsuitable for lobectomy between 1996 and 2005. RESULTS: Ninety-six patients, representing 23% of all patients treated for clinical stage I NSCLC were included in this analysis. The median age was 73 years and most patients were female. Patients underwent limited resection (LR, n = 45), primary radiotherapy (RT, n = 39) or radiofrequency ablation (n = 12). With median follow-up of 30 months, 61 patients remain alive. Actuarial 3-year survival is 65% following LR and 60% after primary RT. Local tumor relapse and distant metastases were observed with approximate equal probability following either LR or RT. CONCLUSION: Medical inoperability does not necessarily correspond to poor survival in patients with early stage NSCLC. A nihilistic approach is not warranted towards this population, and prospective trials are needed to better define optimal treatment strategies.