Manjit S. Bains

Incidence of local recurrence and second primary tumors in resected stage I lung cancer

From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in 25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph node dissection was carried out in 560 patients (94%) and no lymph node dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine percent of the patients were observed for a minimum of 5 years or until death with an overall median follow-up of 91 months. The overall 5- and 10-year survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5 years and 60% at 10 years for patients with T2 tumors (p < 0.0004). The overall incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not influenced by histologic type. Second primary cancers developed in 206 patients (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had recurrence. Five- and 10-year survivals after wedge resection or segmentectomy were 59% and 35%, respectively, significantly less than survivals of those undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals in the 38 patients who had no lymph node dissection were reduced to 59% and 32%, respectively. Apart from the favorable prognosis observed in this group of patients, three facts emerge as significant: (1) Systematic lymph node dissection is necessary to ensure that the disease is accurately staged; (2) lesser resections (wedge/segment) result in high recurrence rates and reduced survival regardless of histologic type; and (3) second primary lung cancers are prevalent in long-term survivors.

Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.

OBJECTIVE The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication. METHODS Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. RESULTS From 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26-93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy. CONCLUSION Patients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned.

Patterns of Initial Recurrence in Completely Resected Gastric Adenocarcinoma

Objective:To review recurrence patterns in completely resected gastric adenocarcinoma. Summary Background Data:Despite improvements in the surgical treatment of gastric adenocarcinoma, recurrence rates remain high in patients with advanced stage disease. Understanding the timing and patterns of recurrence is essential to develop effective adjuvant treatment strategies. Methods:A retrospective review of a prospectively maintained gastric cancer database was carried out. The timing and pattern of recurrence were reviewed. Univariate and multivariate analyses were performed to identify factors predictive of recurrence patterns. Results:From July 1985 through June 2000, 1172 patients underwent an R0 resection. Of these, 496 (42%) had recurrence and complete data on recurrence could be obtained in 367 patients (74%). Among the documented recurrences, 79% were detected within 2 years of operation. Locoregional sites were involved as any part of the recurrence pattern in 199 patients (54%). Distant sites were involved as any part of the recurrence in 188 patients (51%) and peritoneal recurrence was detected as any part of the recurrence in 108 patients (29%). On multivariate analysis, peritoneal recurrence was associated with female gender, advanced T-stage, and distal and diffuse type tumors; locoregional recurrence was associated with male gender and proximal location; distant recurrence was associated with proximal location, early T stage, and intestinal type tumors. The median time to death from the time of recurrence was 6 months. Conclusions:Recurrence after complete resection of gastric adenocarcinoma usually occurs within 2 years and is rapidly fatal. Patterns of recurrence are variable and may be associated with specific clinicopathologic factors.

Preoperative chemotherapy for stage IIIa (N2) lung cancer: The Sloan-Kettering experience with 136 patients

From 1984 to 1991, 136 patients with histologically confirmed non-small cell lung cancer and stage IIIa (N2) disease received two to three cycles of MVP (mitomycin + vindesine or vinblastine + high-dose cisplatin) chemotherapy. All patients had clinical N2 disease, defined as bulky mediastinal lymph node metastases or multiple levels of lymph node involvement in the ipsilateral mediastinum or subcarinal space on chest roentgenograms, computed tomographic scans, or mediastinoscopy. The overall major response rate to chemotherapy was 77% (105/136). Thirteen patients had a complete response and 92 patients had a partial but major response (> 50%). The overall complete resection rate was 65% (89/136) with a complete resection rate of 78% (82/105) in patients with a major response to chemotherapy. There was no histologic evidence of tumor in the resected specimens of 19 patients. The overall survival was 28% at 3 years and 17% at 5 years (median, 19 months). For patients who had complete resection, the median survival was 27 months and the 3-year and 5-year survivals were 41% and 26%, respectively. There were seven treatment-related deaths, five of which were postoperative deaths. To date, 33 patients, all of whom had complete resection, have had no recurrence after treatment. These results demonstrate that (1) preoperative chemotherapy with MVP produces high response rates in stage IIIa (N2) disease, (2) high complete resection rates occur after response to chemotherapy, and (3) survival is longest in patients who have a complete resection after major response to chemotherapy.

Preoperative F-18 Fluorodeoxyglucose-Positron Emission Tomography Maximal Standardized Uptake Value Predicts Survival After Lung Cancer Resection

PURPOSE A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival. PATIENTS AND METHODS Non-small-cell lung cancer or carcinoid pT1-4, N0-2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier. RESULTS One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUV(MAX)) was 9. The 2-year survival for patients with SUV(MAX) more than 9 was 68% and for those with SUV(MAX) less than 9, it was 96% (P <.01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUV(MAX), only tumor size (T) more than 3 cm and SUV(MAX) more than 9 and their interaction were significant predictors of survival (P =.01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUV(MAX) less than 9 was 97%; for those with T less than 3 cm and SUV(MAX) more than 9, it was 94%; for those with T more than 3 cm and SUV(MAX) less than 9, it was 93%; and for those with T more than 3 cm and SUV(MAX) more than 9, it was 47% (P <.01). CONCLUSION In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUV(MAX) to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.

Thymoma: A multivariate analysis of factors predicting survival

BACKGROUND Despite complete surgical excision, malignant thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. METHODS A retrospective analysis of patients operated on for thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazard model. RESULTS One hundred eighteen patients with thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease (p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage (p = 0.003), tumor size (p = 0.0001), histology (p = 0.004), and extent of surgical resection (p = 0.0006) were independent predictors of long-term survival. CONCLUSIONS Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.

Whole Body 18FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial

PURPOSE Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy. PATIENTS AND METHODS Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months. RESULTS PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively). CONCLUSION Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.

Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy

BACKGROUND The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further. METHODS All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events. RESULTS Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate. CONCLUSIONS Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.

Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: Results of a prospective trial

BACKGROUND A retrospective review revealed a 42% error rate between computed tomographic scan reports and thoracotomy findings; therefore, a prospective study was designed to compare the value of computed tomographic scans, video-assisted thoracoscopic exploration, and open thoracotomy in the management of pulmonary metastases. METHODS Eligibility included any patient with only one or two ipsilateral pulmonary metastases identified on computed tomographic scan who was being considered for surgical resection. Initially video-assisted thoracic surgery was performed and all lesions identified were resected. A thoracotomy adequate for complete lung palpation was then carried out and any additional lesions found were removed. RESULTS Eighteen patients of a planned 50 were treated before closure of the study. Four patients (22%) had no additional lesions found at thoracotomy. The primary sites of tumor were colon (10), breast (3), and one patient each skin (squamous), cervix, kidney, melanoma, and sarcoma. Four patients (22%) did have additional lesions at thoracotomy, which were benign. In the remaining 10 patients (56%) additional malignant lesions were found at thoracotomy after video-assisted thoracoscopic exploration. After 18 patients were entered, analysis of the early results disclosed a 56% failure rate of a computed tomographic scan and video-assisted thoracic surgery to detect all lesions. Being within the 95% confidence interval (32% to 78%), the study was abandoned. CONCLUSIONS We conclude that video-assisted thoracic surgery should be used only as a diagnostic tool in managing lung metastasis. A thoracotomy is required to achieve complete resection, which is the major survival prognosticator for satisfactory long-term results.

Proposed Revision Of The Staging Classification For Esophageal Cancer

OBJECTIVES This study analyzed survival with respect to lymph node involvement to develop a new staging system for patients with esophageal cancer that accurately reflects prognosis. METHODS The records of patients undergoing resection of primary esophageal cancer from 1989 to 1993 were reviewed. The data collected included patient age and sex, tumor histologic characteristics and location, the use of preoperative or postoperative radiation and chemotherapy, the type of resection, the depth of tumor invasion, the number and location of benign and malignant lymph nodes in the resected specimen, the disease status at last follow-up, and the first site of relapse. With an anatomically specific lymph node map, tumors designated in the current American Joint Committee on Cancer system as M1 because of extensive lymph node metastases were reclassified as N2, reserving the M1 category for visceral metastases. Survival was analyzed by the Kaplan-Meier method, and prognostic factors were assessed by log-rank and Cox regression analyses. RESULTS There were 216 patients (159 men, 57 women) with a median age of 63.5 years. Adenocarcinoma of the distal esophagus or gastroesophageal junction was the most common tumor (127 patients, 59%) and Ivor Lewis esophagogastrectomy was the most frequently performed operation. Both lymph node location (N1 versus N2) and number (0 vs 1 to 3 vs 4 or more) significantly influenced survival. CONCLUSIONS A new staging system that adds an N2 M0 descriptor and reclassifies stage groupings reflects prognosis more accurately than does the current American Joint Committee on Cancer staging system. The number of positive lymph nodes is also an important stratification factor.