Nael Martini

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.

The Role of Surgery in N2 Lung Cancer

Whereas most physicians believe that long-term survival is unlikely when mediastinal lymph node metastases are present, a significant number of these patients do have resectable tumors with encouraging long-term survival results. Data are presented to support this view, and steps identified to guide the physicians in selecting the patients who can benefit from this surgical approach.

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.

Cisplatin and vindesine combination chemotherapy for advanced carcinoma of the lung: A randomized trial investigating two dosage schedules

Eighty-five patients with advanced squamous carcinoma or adenocarcinoma of the lung were randomly assigned to receive vindesine with either high dose (120 mg/m2 of body surface area) or low dose (60 mg/m2) cisplatin. All patients had measurable disease and had not previously received chemotherapy. The response rate was similar with both treatments (43% complete and partial remission rate), but the high dose cisplatin regimen was superior to the low dose in median duration of response (12 versus 5.5 months; p = 0.05) and in median survival for responding patients (21.7 versus 10 months; p = 0.02). Myelosuppression was generally not a treatment problem; peripheral neuropathy and moderate azotemia were the major dose-limiting toxicities. With improved survival and response rates over those reported for conventional regimens, this combination of new agents supports the approach of new drug investigation in patients with lung cancer and the importance of the incorporation of active new agents into initial chemotherapy regimens.

Results of resection in non-oat cell carcinoma of the lung with mediastinal lymph node metastases.

From 1974 to 1981, 1598 patients with non-oat cell carcinoma of the lung were seen and treated. All were staged according to the AJC staging system. Of these, 706 patients had evidence of mediastinal lymph node metastases (N2). There were 151 patients (21%) who had complete, potentially curative resection of their primary tumor and all accessible mediastinal lymph nodes. The histologic type of tumor was adenocarcinoma in 94 patients, epidermoid carcinoma in 46 patients, and large-cell carcinoma in 11 patients. The extent of pulmonary resection consisted of a lobectomy in 119 patients, pneumonectomy in 26 patients, and wedge resection or segmentectomy in six patients. Almost all patients also received radiation therapy to the mediastinum. Clinical staging of the primary tumor and the mediastinum was based on the radiographic presentation of the chest and on bronchoscopy. Before treatment, 104 of 151 patients (69%) were believed to have had stage I (90 patients) or II (14 patients) disease, and 47 patients had stage III disease, of whom only 33 had evidence of mediastinal lymph node involvement. Excluding deaths from unrelated causes, the overall survival rate was 74% at 1 year, 43% at 3 years and 29% at 5 years. Survival in patients with clinical stage I or II disease treated by resection was favorable despite the presence of N2 nodes (50% at 3 years). Survival in obvious clinical N2 disease was poor (8% at 3 years). There was no difference in survival between patients with adenocarcinoma and those with epidermoid carcinoma. However, survival was poorer in patients with N2 nodes in the inferior mediastinum compared to those without lymph node involvement at that level.

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.

Multiple Pulmonary Resections in the Treatment of Osteogenic Sarcoma

Abstract More than 80% of patients with osteogenic sarcoma develop pulmonary metastases within two years and, if untreated, die from their disease within a few months. With surgical resection of pulmonary metastases, solitary or multiple, nearly half the patients we treated were alive and free of disease two years after resection. Radiotherapy and chemotherapy have been of limited value in treating metastatic osteogenic sarcoma. Early detection of pulmonary metastases by roentgenographic follow-up examination at frequent intervals and surgical excision of all metastases, by repeated thoracotomies if necessary, appear to be the treatment of choice.

Thymomas: Clinicopathologic features, therapy, and prognosis

Fifty‐four patients with thymoma were seen at Memorial Hospital from 1928 to 1972. There were 18 benign and 36 malignant thymomas. Benign tumors were completely encapsulated. Malignant tumors were non‐encapsulated or incompletely encapsulated and invasive. All patients with benign thymoma were treated by resection alone. None had recurrent disease or died with tumor for periods ranging from 5 to 17 years after resection. Patients with malignant thymoma treated by resection alone had recurrent tumor within 5 years and subsequently died of their disease. All malignant thymoma patients who were alive free of disease for 5 or more years had radiation therapy and resection. Clinicopathologic features indicating a poor prognosis were: a non‐encapsulated tumor of a predominantly epithelial cell type, superior vena caval syndrome, malignant pleural effusion, supraclavicular lymph node involvement, dysphagia, hoarseness, myasthenia gravis, erythroid hypoplasia, and hypogammaglobulinemia.

Cellular schwannoma: a variety of schwannoma sometimes mistaken for a malignant tumor.

Fourteen cellular schwannomas, a variety of peripheral nerve sheath tumor showing a predominantly compact cellular growth, no formed cellular palisades or Verocay bodies, but the ultrastructure of schwannomas, are reported. A presumed nerve of origin was identified in three instances. The tumor had no sex predeliction; the mean age was 48. The neoplasm is usually well encapsulated and most commonly presents in the neck, posterior mediastinum, or pelvis. Because of a variety of confusing histologic features, including dense cell bundles and fascicles, storiform areas, a moderate mitotic activity and moderate nuclear atypia, six of 14 cases were mistaken for either fibrous histiocytoma, leiomyoma, malignant peripheral nerve sheath tumor, or sarcoma of uncertain type. In two instances the false impression of a malignant tumor was reinforced by clinical evidence of bony erosion and destruction. Follow-up thus far has shown the tumor to be benign.

VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors.

One hundred sixty-six patients with germ-cell tumors (GCT) of the testis, retroperitoneum, and mediastinum were treated with cyclophosphamide, vinblastine, bleomycin, dactinomycin, and cisplatin (VAB-6), with and without maintenance chemotherapy. The overall complete response (CR) rate was 78%, 67% to chemotherapy alone, and 11% after chemotherapy and resection of viable residual cancer. The CR rate in all patients with seminoma was uniformly high, while the CR rate of patients with testicular nonseminomatous germ-cell tumors (79%) was superior to that of similar tumors of extragonadal origin (60%). The overall relapse rate was 12%, and was greater in tumors of extragonadal origin (21%) than in those of testicular origin (11%). Three relapses occurred after 2 years. Maintenance chemotherapy did not prolong either relapse-free or total survival. Toxicity was tolerable, and there were no treatment deaths. No Raynauds phenomena have occurred, with a minimum duration since start of therapy of 36 months. VAB-6 is an effective chemotherapy regimen in patients with GCT with no treatment-related deaths and a majority of patients requiring only 3 months of treatment.