Michael Semik

Osteosarcoma Relapse After Combined Modality Therapy: An Analysis of Unselected Patients in the Cooperative Osteosarcoma Study Group (COSS)

PURPOSE To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.

Tumor Recurrence and Survival in Patients Treated for Thymomas and Thymic Squamous Cell Carcinomas: A Retrospective Analysis

PURPOSE Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer

BACKGROUND Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. METHODS Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137. FINDINGS 558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p<0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]). INTERPRETATION In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided. FUNDING German Cancer Aid (Bonn, Germany).

Recurrent Genetic Aberrations in Thymoma and Thymic Carcinoma

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma.

Prognostic impact of Cyfra21-1 and other serum markers in completely resected non-small cell lung cancer.

PURPOSE The aim of this prospective study was to assess the prognostic impact of serum tumor markers (Cyfra21-1, carcinoembryonic antigen, neuron-specific enolase, squamous cell carcinoma-antigen and TPAcyk) in patients with non-small cell lung cancer (NSCLC) receiving complete resection. METHODS Sixty-seven patients with histologically proven NSCLC and complete resection of stage I-IIIA disease were included. The serum levels of all markers were measured using commercially available immunoassays. RESULTS With a median follow-up of 86 months for surviving patients, those with initial Cyfra21-1 serum levels higher than 3.57 ng/ml had a significantly worse prognosis (P=0.014). The remaining serum tumor markers showed no prognostic impact. In a Cox regression model, Cyfra21-1 proved to be an independent prognostic factor for both overall survival and disease-free interval. In addition, Cyfra21-1 sustained as an independent prognostic factor in completely resected stage I/II disease. CONCLUSIONS With a cut-off value of 3.57 ng/ml, Cyfra 21-1 was an independent prognostic factor for survival in NSCLC-patients with complete resection. Further evaluation is needed, particularly in stage I/II disease. When the prognostic impact is confirmed with larger patient numbers this may contribute to the identification of stratification variables for future treatment approaches of NSCLC.

Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.

Screening for asymptomatic early bronchogenic carcinoma with low dose CT of the chest.

Survival of patients with lung carcinoma is very poor, particularly for patients with advanced disease. There are no early clinical symptoms, and screening with chest radiography has not been recommended. Computed tomography (CT) is superior to radiography for detection of pulmonary nodules but usually is associated with relatively high radiation exposure. Recently, accuracy of low dose CT has been shown to be similar to conventional dose CT. The goal of the current study was to assess the findings of low dose CT of the chest in heavy smokers.

Lung cancer surgery--preoperative risk assessment and patient selection.

Lung resection remains the therapy of choice offering the greatest potential for cure in non spread lung cancer. As these procedures have a significant rate of cardiopulmonary complications, risk assessment and evaluation of functional operability is essential for successful resectional surgery. The most valuable parameters for evaluation of lung function and risk assessment are FEV1, DLCO and VO2max as well as the calculation of predicted postoperative lung function. With preoperative preparatory physical therapy and treatment of comorbidities, also marginal patients may become operable for resectional surgery.

Single-Lung Ventilation for Pulmonary Lobe Resection in a Newborn

UNLABELLED The increasing frequency of video-assisted thoracoscopic interventions as well as open thoracic surgical procedures in children demands appropriate anesthetic techniques to provide single-lung ventilation. A fiberoptically directed, wire-guided 5F endobronchial blocker for use in small infants has recently been devised. We report on the very special aspects of airway management in a newborn 3000-g infant who presented a major anesthetic and surgical challenge because of congenital emphysema of the left upper pulmonary lobe. IMPLICATIONS The special aspects of single-lung ventilation in a newborn 3000-g infant who presented a major anesthetic and surgical challenge because of congenital emphysema of the left upper pulmonary lobe are reported.

Spontaneous Splenic Rupture After a Left-Side Thoracotomy: Report of a Case

We herein describe the case of a 59-year-old man who experienced a spontaneous splenic rupture 12 h after undergoing a left-side thoracotomy for a wedge resection of an unknown pulmonary nodular tumor following a history of malignant melanoma. He demonstrated no special abdominal diseases or traumas, except an uneventful cholecystectomy 12 years previously. Preoperatively, he was not on anticoagulation, aspirin, or nonsteroidal anti-inflammatory medication, and all coagulation tests were inconspicuous. At 12 h after lung surgery the patient showed signs of progredient hypovolemic shock. After ultrasonography, which showed a moderate amount of free intra-abdominal liquid, the patient was urgently taken to the operation room. Bleeding resulted from a rupture of an encapsulated hematoma from the spleen. No signs of adhesion around the spleen or of an injury of the left diaphragm were observed. A pathological analysis of the spleen revealed a normal dimension and a normal histological structure without any evidence of a hematological or neoplastic disease. The patient was discharged on the 12th day after surgery. A review on the literature and the differential diagnosis of this unusual case is presented and discussed.