Leslie J. Kohman

Effect of Number of Lymph Nodes Sampled on Outcome in Patients With Stage I Non–Small-Cell Lung Cancer

PURPOSE We postulate that surgical sampling and pathologic evaluation of lymph nodes of surgical specimens from patients with stage I non-small-cell lung cancer (NSCLC) can have an effect on the time to recurrence and survival of these patients. PATIENTS AND METHODS We analyzed data on 442 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. Associations between total lymph nodes sampled and disease-free survival (DFS) and overall survival (OS) were investigated. The effect of total lymph node stations sampled and the surgical techniques (random lymph node sampling, systematic sampling [SS], or complete mediastinal lymph node dissection [MLND]) on DFS and OS was also studied. Complete MLND and SS were defined as dissection or sampling of levels 4, 7, and 10 for right-sided lesions and levels 5 or 6 and 7 for left-sided lesions. RESULTS Patients were divided into quartiles on the basis of total number of lymph nodes sampled. Improved DFS and OS were associated with greater number of lymph nodes sampled. SS and MLND were associated with improved survival compared with random lymph node sampling. The total number of lymph nodes sampled maintained strong significance in the multivariate analysis. CONCLUSION These results indicate that examining a greater number of lymph nodes in patients with stage I NSCLC treated with resection increases the likelihood of proper staging and affects patient outcome. Such information is important not only for therapy and prognosis of individuals but also for identifying those who may benefit from adjuvant therapy.

Results of cancer and leukemia group B protocol 8935 ☆ ☆☆ ★ ★★ ♢ ♢♢ ♦: A multiinstitutional phase II trimodality trial for stage IIIa (N2) non-small-cell lung cancer

From October 1989 to February 1992, 74 patients with mediastinoscopically staged IIIA (N2) non-small-cell lung cancer from 30 CALGB-affiliated hospitals received two cycles of preresectional cisplatin and vinblastine chemotherapy. Patients with responsive or stable disease underwent standardized surgical resection and radical lymphadenectomy. Patients who underwent resection received sequential adjuvant therapy with two cycles of cisplatin and vinblastine, followed by thoracic irradiation (54 Gy after complete resection and 59.4 Gy after incomplete resection or no resection at 1.8 Gy per fraction). There were no radiographic complete responses to the neoadjuvant chemotherapy, although 65 (88%) patients had either a response or no disease progression. During induction chemotherapy, disease progressed in seven patients (9%). Sixty-three patients (86%) had exploratory thoracotomy, and 46 of those (75%) had resectable lesions. A complete surgical resection was accomplished in 23 patients, and 23 patients had an incomplete resection with either a diseased margin or diseased highest node resected. Operative mortality was 3.2% (2/63). In 10 patients (22% of the 46 having resection) the disease was pathologically downstaged. There was no correlation between radiographic response to the induction chemotherapy and downstaging at surgical resection. The full protocol was completed by 33 patients (45% of original cohort). Overall survival at 3 years was 23%. Patients undergoing resection had significantly improved survival at 3 years compared with patients not having resection: 46% for complete resection (median 20.9 months), 25% for incomplete resection (median 17.8 months), and 0% for no resection (median 8.5 months). Five deaths occurred during the treatment period. A total of 18 of the 46 (39%) patients who underwent resection are either alive and disease-free or have died without recurrence.

Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

PURPOSE The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non-squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

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.

Preoperative Exercise Vo2 Measurement for Lung Resection Candidates: Results of Cancer and Leukemia Group B Protocol 9238

Introduction: A stepwise approach to the functional assessment of lung resection candidates is widely accepted, and this approach incorporates the measurement of exercise peak Vo2 when spirometry and radionuclear studies suggest medical inoperability. A new functional operability (FO) algorithm incorporates peak exercise Vo2 earlier in the preoperative assessment to determine which patients require preoperative radionuclear studies. This algorithm has not been studied in a multicenter study. Methods: The CALGB (Cancer and Leukemia Group B) performed a prospective multi-institutional study to investigate the use of primary exercise Vo2 measurement for the prediction of surgical risk. Patients with known or suspected resectable non-small cell lung cancer (NSCLC) were eligible. Exercise testing including measurement of peak oxygen uptake (Vo2), spirometry, and single breath diffusion capacity (DLCO) was performed on each patient. Nuclear perfusion scans were obtained on selected high-risk patients. After surgery, morbidity and mortality data were collected and correlated with preoperative data. Mortality and morbidity were retrospectively compared by algorithm-based risk groups. Results: Three hundred forty-six patients with suspected lung cancer from nine institutions underwent thoracotomy with or without resection; 57 study patients did not undergo thoracotomy. Patients who underwent surgery had a median survival time of 30.9 months, whereas patients who did not undergo surgery had a median survival time of 15.6 months. Among the 346 patients who underwent thoracotomy, 15 patients died postoperatively (4%), and 138 patients (39%) exhibited at least one cardiorespiratory complication postoperatively. We found that patients who had a peak exercise Vo2 of <65% of predicted (or a peak Vo2/kg <16 ml/min/kg) were more likely to suffer complications (p = 0.0001) and were also more likely to have a poor outcome (respiratory failure or death) if the peak Vo2 was <15 ml/min/kg (p = 0.0356). We also found a subset of 58 patients who did not meet FO algorithm criteria for operability, but who still tolerated lung resection with a 2% mortality rate. Conclusions: Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients, and we encourage an aggressive approach when evaluating these patients for surgery.

Peak Oxygen Consumption and Long-Term All-Cause Mortality in Nonsmall Cell Lung Cancer

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 [VO2peak]) among operable candidates with NSCLC.

Multicenter VATS experience with mediastinal tumors

BACKGROUND The use of video-assisted thoracic surgery for diagnosis and treatment of mediastinal tumors in a multiinstitution patient population is not well understood. METHODS We studied 48 cases from Cancer and Leukemia Group B thoracic surgeons. Of 21 men and 27 women, aged 41 +/- 16 years, 22 patients were asymptomatic. In the others, 92% of tumor-related symptoms improved or resolved after treatment. Five tumors involved the anterior compartment, 19 the middle, and 24 the posterior compartment. Diagnoses were typical for each compartment but also included uncommon problems such as superior vena cava hemangioma and a histoplasmosis cyst causing hoarseness. Of the lesions, a biopsy of 12 was done without excision and the rest were excised completely. Fifteen were cystic and 10 were malignant (8 biopsy only). Maximal dimensions were 5.2 +/- 3.3 cm. RESULTS Operations were briefer for 24 posterior (93 +/- 41 min) than 5 anterior (195 +/- 46 min, p < 0.01) or 19 middle mediastinal tumors (170 +/- 78 min, p < 0.01). Although 96% had vital mediastinal relations, only six open conversions were performed because of bleeding (n = 3), large size, impaired exposure, or rib attachments, and no patient had morbidity beyond that expected for the thoracotomy. Postoperative stay was shorter for the nonconversion group (3.2 +/- 2.8 versus 5.5 +/- 2.1 days, p = 0.05), as was chest tube duration (1.7 +/- 1.4 days versus 3.2 +/- 1.9 days, p = 0.03). There were no postoperative deaths or major complications, but 7 patients had minor complications. During a mean of 20 months of surveillance (range, 1 to 52 months), one cyst recurred (asymptomatic) as did one sarcoma that was excised. CONCLUSIONS Video-assisted thoracic surgery is a safe technique for benign mediastinal tumors, typically those in the middle and posterior mediastinum.

Bacteremia and sternal infection after coronary artery bypass grafting

Sternal wound infection remains a source of substantial morbidity and mortality after coronary artery bypass grafting. We noted an association between bacteremias and sternal wound complications in these patients. A review of 835 consecutive coronary bypass patients showed a 3.2% incidence of bacteremia and a 1.9% incidence of deep and superficial sternal wound infection. The sternal wound was the most common source of bacteremia, accounting for 59% of the infections. Coagulase-negative Staphylococcus was responsible for one half of the sternal wound infections. Often, a positive blood culture was the first manifestation of wound infection, occurring before local signs were manifest. We recommend multiple blood cultures in postoperative coronary bypass patients with pronounced fever. If no source of infection can be identified, sternal wound aspirate may be revealing. Appropriate early wound management can then be carried out, maximizing chances for good recovery.

Magnetic resonance imaging of prosthetic cardiac valves in vitro and in vivo

Abstract Although radiologists do not hesitate to recommend or perform a magnetic resonance imaging (MRI) examination on most patients, there have been reservations—on theoretical grounds—regarding MRI examinations for patients in whom prosthetic cardiac valves have been implanted. It is not known whether MRI is hazardous in the presence of a prosthetic valve. The questions that need to be resolved are whether these valves might malfunction when placed in a strong magnetic field, how much heat might be produced in the valves by radiofrequency pulses, whether induced electric currents might cause arrhythmias and whether unacceptable distortion of adjacent tissue might be generated in the image. Based on the preliminary in vitro work by Soulen et al,1 it seemed that MRI would be safe in patients with prosthetic valves. Other in vitro work by Hassler et al2 and the clinical work by Laakman et al3 in patients with other metallic implants also suggested that MRI in patients with prosthetic valves would be safe as well as display minimal metallic artifact. We undertook a 2-part study to examine the 5 prosthetic valves used at our institution. The valves were evaluated in vitro for heat production, deflection, torque (or a combination of these) that might present a hazard to the patient. Images of the valves were obtained in a saline bath under imaging conditions identical to those used in the in vivo studies. These images demonstrated the kinds of artifacts that would be produced by the valves and formed a baseline with which the patient images could be compared. In vivo, we studied the appearance of the valves and adjacent tissues. Patients were monitored for electrocardiogram changes as well as other symptoms.

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.