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Objective: Different types of multimodality therapy, including chemoradiotherapy and surgery, increasingly are being used for the treatment of patients with locally advanced non-small cell lung cancer (NSCLC; stages IIIA and IIIB). In this context, the applicability of a morphologic regression grading and its prognostic value were investigated.Patients and Methods: In a multicenter phase II trial, 54 patients with locally advanced NSCLC received neoadjuvant bimodality treatment (ie, two cycles of ifosfamide, carboplatin, and etoposide, followed by twice-daily radiation up to 45 Gy with simultaneous administration of carboplatin and vindesine). Forty patients underwent resections. Using the corresponding resection specimens of the primary and regional lymph nodes, the following regression grading was established: grade I, no regression or only spontaneous tumor regression; grade II, morphologic evidence of therapy-induced tumor regression with at least 10% (grade IIa) or < 10% (grade IIb) vital tumor tissue; and grade III, complete tumor regression with no evidence of vital tumor tissue. Regression grading then was correlated with the survival time.Results: Three tumors were classified as regression grade I, 10 were classified as regression grade IIa, 20 were classified as regression grade IIb, and 7 were classified as regression grade III. Patients with tumors of regression grades IIb or III showed significantly longer survival times than those with tumors of regression grades I or IIa (median survival time, 36 vs 14 months, respectively; 3-year survival rate, 52% vs 9%, respectively; p = 0.02). These survival times were also compared for patients who had undergone complete resection (median survival time, not reached vs 23 months, respectively; 3-year survival rate, 56% vs 11%, respectively; p = 0.03). The presurgical clinical response after patients had received neoadjuvant multimodality therapy had no predictive value in assessing the extent of therapy-induced tumor regression in the resection specimen.Conclusions: After neoadjuvant therapy of patients with NSCLC, the proposed tumor regression grading was of predictive value for long-term survival. Beyond the achievement of complete tumor resection (R0), a therapy-induced tumor regression of < 10% of vital tumor tissue is pivotal for superior long-term outcomes. [ABSTRACT FROM AUTHOR]

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Objective: Patients with small cell lung cancer (SCLC) are frequently denied surgical treatment despite growing body of evidence for a longer duration of remission and overall survival, if surgical intervention is integrated in a tri-modality therapy concept including chemotherapy, surgery, and radiotherapy., Methods: A retrospective analysis was performed using data derived from 95 patients with SCLC operated upon over a period of 9 years. A subset of these patients was primarily operated upon and being diagnosed as SCLC only after thoracotomy, received radio-/chemotherapy postoperatively (n=64, group I). The second cohort had surgery after neoadjuvant chemotherapy which was continued postoperatively in addition to thoracic and cranial radiotherapy (n=31, group II). The patients in the second group were further divided into two subgroups: complete histological regression of tumor tissue in the mediastinal lymph nodes (group IIA), and those with persistent mediastinal lymph nodal involvement detected after thoracotomy (group IIB)., Results: Group I patients had stage I or II disease, whereas group II patients had clinical stage IIIA or IIIB. The overall 30-day mortality rate was as low as 5%. The median survival was 31.3 months for patients in group I, 31.7 months for adjuvant surgery with complete regression of mediastinal nodes (group IIA), and 12.4 months for adjuvant surgery without regression of mediastinal nodes (group IIB)., Conclusions: Surgical intervention is promising and warrants prospective trials to be evaluated as an important adjunct to multi-modality therapy regimen in SCLC as regards to its impact on relapse free and overall survival.

The German Lung Cancer Cooperative Group (GLCCG) is assessing the impact of chemoradiation in addition to chemotherapy in the neoadjuvant treatment of stage III NSCLC. After three cycles of cisplatin/etoposide patients receive either hyperfractionated radiotherapy (RT) with concurrent carboplatin/vindesine and then surgery (arm A) versus surgery and then conventional RT (arm B). Quality of life (QL) was assessed throughout therapy using the EORTC QLQ-C30 and EORTC QLQ-LC 13. Of 126 eligible patients, 54 completed treatment. For patients in both treatment arms physical functioning decreased, whereas dyspnoea, fatigue and pain increased from beginning to the end of treatment. For self-assessed QL no statistically significant effect was found in or between the two treatment arms. The combined modality approach with preoperative radio/chemotherapy proves to be feasible in treating locally advanced NSCLC patients without decreasing their subjective QL.

Background: The relevance of a trimodal strategy in the treatment of lung cancer, consisting of neoadjuvant radiochemotherapy followed by surgery, is a subject of ongoing clinical trials. We tested whether improvement of long-term survival can be achieved for patients with stage III non-small cell lung cancer by this therapeutic approach., Methods: We performed a retrospective analysis of a single-institution phase II study. Of 33 patients enrolled in the protocol between 1992 and 1995, we reviewed the clinical outcomes of 26 patients with locally advanced non-small cell lung cancer (stage IIIA and IIIB), which had been resected after combined chemotherapy and radiochemotherapy., Results: After neoadjuvant therapy, resection of the tumor was accomplished in all patients, and R0 resection was achieved in 92%. Histologic remission was found in 76% of these patients. Involvement of mediastinal lymph nodes was crucially important for the outcome. First, histologic clearance of the mediastinal compartment by neoadjuvant therapy resulted in a 27% 5-year survival rate. Second, patients with viable tumor in any of the mediastinal lymph nodes removed had a poor outcome (median survival 11.4 and 34.7 months in patients with and without viable tumor cells in the specimens, respectively; p = 0.01)., Conclusions: Histopathologic regression after neoadjuvant multimodal therapy including chemotherapy and radiotherapy was an important prognostic factor in a selected group of patients with locally advanced lung cancer.

Background: In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated., Methods: Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis., Results: K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005)., Conclusions: These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches., (Copyright 2002 American Cancer Society.)

Purpose: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC)., Patients and Methods: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable., Results: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%., Conclusion: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.

Purpose: In the last years new encouraging methods in the therapy of bronchial carcinoma have been elaborated. The early stages of bronchial carcinoma are still a domain of operative treatment. The long-term results of surgical treatment for locally advanced disease are considered to be unfavourable. Multimodal treatment concepts with simultaneous or consecutive application of radio-chemotherapy followed by surgical resection seem to reveal improved possibilities of therapy., Patients and Methods: General treatment consists of 2 blocks of neoadjuvant chemotherapy with carboplatin, ifosfamide and etoposide, followed by a third course, consisting of carboplatin and vindesine. Simultaneously with the third course a hyperfractionated, accelerated radiotherapy with a single dose of 1.5 Gy 10 times per week is applied. The total dose is 45 Gy in 3 weeks, given at least to the 80% isodose. After restaging, tumor resection is carried out. Patients without tumor are randomized for prophylactic brain irradiation., Results: From January 1992 up to 1.10.1993 25 patients have been treated in accordance to the study. All tumors were locally advanced (stage IIIa and IIIb). Until 1.10.1993 4 patients died, 2 of them certainly related to the tumor. Thirteen patients have been resected after neoadjuvant treatment. In 11 of these cases a R0-, and in 2 cases a R1 resection has been carried out. Tumor cells have been found only in 5 histologies. The hematotoxic side effects under competing RTX/CTX seemed to be unproblematical (RTOG/grade II). Problems occurred with 4 cases of serious esophagitis (RTOG/grade III to IV) and 2 cases of pneumonitis with 1 case ending lethally., Conclusion: Preliminary results of our study show the feasibility of multimodal treatment. A favourable 1-year survival rate after aggressive multimodal therapy and a high resection rate in previously unresectable patients could be demonstrated.

Since the entire surface of the bronchial mucosa is exposed to carcinogenic stimuli, the possibility of developing multiple primary lung carcinomas must be discussed. Multiple primary lung carcinomas do not necessarily occur simultaneously (synchronous), they can also develop successively (metachronous). They can be localized ipsilateral as well as contralateral, and histologically they have an identical or different character. In our study of 612 patients with bronchogenic carcinoma we found 18 patients (2.9%) to have a synchronous multiple primary carcinoma. The growing clinical relevance of the diagnosis of the multiple primary bronchogenic carcinoma--which is certainly diagnosed to rarely--and the distinction from metastases will be discussed.

Tumorlets of the lungs are multifocal hyperplasias of endocrine cells which may develop via nodular hyperplasia into peripheral, occasionally also metastatic, carcinoids. They are observed with a particular frequency in bronchiectasis. Resected material obtained from patients with bronchiectasis (4 women, 3 men, mean age 43.5 years, range 19-66 years) were submitted to conventional histological studies employing HE, PAS and van Gieson staining, and also to an immunohistological analysis. Conventional staining sufficed to identify endocrine cell proliferations in the scarred lung tissue in 3 preparations. An assignment to bronchioles and alveoli with conventional histology was, in view of the extensive scarring of the lung parenchyma, very difficult, but was accomplished with the aid of immunohistological investigation. As a multifocal tumour, the tumourlet suggests itself as a model, employing immunohistochemistry, for studying the formal genesis of neuroendocrine tumours of the lung, since it shows the earliest intra-epithelial neoplastic transformations through in situ tumour to carcinoid.

A carcinoid of the thymus was studied by light- and electron-microscopy, immunohistology and flow-cytometry. The tumor showed a ribbon- and festoon-like growth-pattern with foci of necrosis, invasion of vessels and infiltration of mediastinal lymph nodes. The cytoplasma of the tumor-cells contained neuroendocrine granula and immunohistochemistry of ACTH was positive. The tumor-cells were connected by desmosomes, correlating to a pre-keratin positive immunohistology. In flow-cytometry the tumor-cells showed a near haploid DNA aneuploidy which is an extremely rare finding in solid tumors and in the few cases described indicative for treatment resistance.