UZ Leuven

Prospective comparative study of integrated PETCT versus re-mediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy proven stage IIIa-N2 non-small cell lung cancer. De Leyn P, Stroobants S, De Wever W, Lerut T, Coosemans W, Decker G, Nafteux P, Van Raemdonck D, Mortelmans L, Nackaerts K, Vansteenkiste J. A Leuven Lung Cancer Group Study. JCO 2006, in Press (publication date July 2006). J Clin Oncol 2006;24:3333-9. Abstract: PURPOSE: Mediastinal restaging after induction therapy for non-small-cell lung cancer remains a difficult and controversial issue. The goal of this prospective study was to compare the performance of integrated positron emission tomography (PET)-computed tomography (CT) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy. PATIENTS AND METHODS: Thirty consecutive stage IIIA-N2 nonsmall- cell lung cancer patients surgically treated at our institution were entered onto this prospective study. N2 disease was proven by cervical mediastinoscopy, at which a mean number of 3.8 lymph node levels were biopsied. After completion of induction chemotherapy, the mediastinum was reassessed by integrated PET-CT and remediastinoscopy. All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection. RESULTS: PET-CT showed no evidence of nodal disease (N0) in 13 patients, Hilar nodal disease (N1) disease in three patients, and residual mediastinal disease (N2) in 14 patients. Remediastinoscopy was positive in only five patients. The preinduction involved lymph node level could be accurately re-evaluated in 18 patients. This was not the case in the other 12 because of extensive fibrosis and adhesions. In 17 patients, persistent N2 disease was found at thoracotomy. The sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively. These parameters for remediastinoscopy were 29%, 100%, and 60%, respectively. Sensitivity (P < .0001) and accuracy (P = .012) were significantly better for PET-CT. CONCLUSION: After a thorough staging mediastinoscopy, postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis. Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images.

Histopathologic Validation of Lymphnode Staging with FDG-PET-scan in Cancer of the Esophagus and Gastroesophageal Junction. Lerut A, Flamen P, Ectors N, Van Cutsem E, Peeters M, Hiele M, De Wever W, Coosemans W, Decker G, De Leyn P, Deneffe G, Van Raemdonck D, Mortelmans L. Ann Surg 2000;232(6):743-752.Abstract: OBJECTIVE: To assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. SUMMARY BACKGROUND DATA: FDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. METHODS: Forty-two patients entered the prospective study. All underwent attenuation-corrected FDGPET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). RESULTS: The FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1-2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDGPET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1-2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. CONCLUSIONS: FDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Extracapsular lymph node involvement is a negative prognostic factor in T3 adenocarcinoma of the distal esophagus and gastro-esophageal junction. Lerut T, Coosemans W, Decker G, De Leyn P, Ectors N,

Fieuws S, Moons J, Nafteux P, Van Raemdonck D and

the Leuven Collaborative Workgroup for Esophageal

Carcinoma. J Thorac Cardiovasc Surg 2003;126(4):1121 – 1128. Abstract: OBJECTIVE: To assess prognosis according to whether lymph node involvement is intracapsular or with extracapsular breakthrough in adenocarcinoma of the distal esophagus and gastroesophageal junction. Materials and methods One hundred ninety-five consecutive patients with T3 adenocarcinoma of the distal esophagus and gastroesophageal junction between 1990 and 1999 were studied. All patients underwent primary R0 esophagectomy. The mean number of resected nodes per patient was 36.9. Survival was analyzed according to intracapsular and extracapsular involvement. RESULTS: In N0 patients 5-year survival was 57% and 9-year survival was 38.7%. In patients with positive nodes these figures were 26.2% and 18.1%, respectively (P =.0069). Intracapsular and extracapsular node involvement showed 5- and 10-year survival of 40.9% and 21.7% versus 18% and 15.7%, respectively. There was no significant difference in 5- and 10-year survival between N0 and intracapsular node involvement (P =.43). However, there was a significant difference in survival between N0 and extracapsular node involvement (P =.002) and between intracapsular and extracapsular node involvement (P =.0001). CONCLUSIONS: This study shows a significant difference in survival according to whether lymph node involvement was intracapsular or extracapsular. Patients with intracapsular lymph node involvement have similar survival rates as N0 patients. Extracapsular lymph node involvement is a bad prognostic factor, independent of the number of involved lymph nodes. The number of involved lymph nodes has an additive negative effect. These data may have an impact on treatment strategies.

Three-field lypmhadenectomy for carcinoma of the esophagus and gastro-esophageal junction in 174 R0 resections. Impact on TNM staging and outcome. Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux P, Moons J, Van Raemdonck D. Ann Surg 2004;240(6):962-972.Abstract: OBJECTIVE: To determine the impact of esophagectomy with 3-field lymphadenectomy on staging, disease-free survival, and 5-year survival in patients with carcinoma of the esophagus and gastroesophageal junction (GEJ). BACKGROUND: Esophagectomy with 3-field lymphadenectomy is mainly performed in Japan. Data from Western experience with 3-field lymphadenectomy are scarce and dealing with relatively small numbers. As a result, its role in the surgical practice of cancer of the esophagus and GEJ remains controversial. METHODS: Between 1991 and 1999, primary surgery with 3-field lymphadenectomy was performed in 192 patients, of whom a cohort of 174 R0 resections was used for further analysis. RESULTS: Hospital mortality of the whole series was 1.2%. Overall morbidity was 58%. Pulmonary complications occurred in 32.8%, cardiac dysrhythmias in 10.9%, and persistent recurrent nerve problems in 2.6%. pTNM staging was as follows: stage 0, 0.6%; stage I, 9.2%; stage II, 27.6%; stage III, 28.7%; and stage IV, 33.9%. Overall 3- and 5-year survival was 51% and 41.9%, respectively. The 3- and 5-year disease-free survival was 51.4% and 46.3%, respectively. Locoregional lymph node recurrence was 5.2%; no patient developed an isolated cervical lymph node recurrence. Five-year survival for node-negative patients was 80.2% versus 24.5% for node-positive patients. Five-year survival by stage was 100% in stages 0 and I, 59.1% in stage II, 36.8% in stage III, and 13.3% in stage IV. Twenty-three percent of the patients with adenocarcinoma (25.8% distal third and 17.6% GEJ) and 25% of the patients with squamous cell carcinoma (26.2% middle third) had positive cervical nodes resulting in a change of pTNM staging specifically related to the unforeseen cervical lymph node involvement in 12%. Cervical lymph node involvement was unforeseen in 75.6% of patients with cervical nodes at pathologic examinations. Five-year survival for patients with positive cervical nodes was 27.7% for middle third squamous cell carcinoma. For distal third adenocarcinomas, 4-year survival was 35.7% and 5-year survival 11.9%. No GEJ adenocarcinoma with positive cervical nodes survived for 5 years. CONCLUSIONS: Esophagectomy with 3-field lymph node dissection can be performed with low mortality and acceptable morbidity. The prevalence of involved cervical nodes is high, regardless of the type and location of tumor resulting in a change of final staging specifically related to the cervical field in 12% of this series. Overall 5-year and disease-free survival after R0 resection of 41.9% and 46.3%, respectively, may indicate a real survival benefit. A 5-year survival of 27.2% in patients with positive cervical nodes in middle third carcinomas indicates that these nodes should be considered as regional (N1) rather than distant metastasis (M1b) in middle third carcinomas. These patients seem to benefit from a 3-field lymphadenectomy. The role of 3-field lymphadenectomy in distal third adenocarcinoma remains investigational.

Results of induction chemotherapy followed by surgery in patients with stage IIIA N2 NSCLC: importance of pre-treatment mediastinoscopy. De Leyn P, Vansteenkiste J, Deneffe G, Van Raemdonck D, Coosemans W, Lerut T. Eur J Cardiothorac Surg 1999;15(5):608-614. Abstract: OBJECTIVE: Data from the literature indicate that chemotherapy prior to resection may improve the results. However, only few and conflicting data are reported regarding the correlation between downstaging of mediastinal nodes and outcome. The aim of this study was to look at the correlation between downstaging, survival and pre-treatment staging. MATERIAL AND METHODS: Between March 1995 and August 1998, 46 consecutive patients with pathology proven N2 disease were treated with three cycles of vindesine-ifosfamide-platinum (VIP). All patients underwent a rigorously performed cervical mediastinoscopy. Patients with at least partial response (n = 26) were surgically explored. RESULTS: The clinical response rate to chemotherapy was 57% (26 patients). Resection was complete in 23 patients (88.5%). Pneumonectomy was performed in 16 patients. In 11 patients (42.9%) the mediastinal nodes (which were positive at mediastinoscopy) had become negative (downstaging group). The projected 2-year survival of resected patients is 41%. Patients with downstaging of nodes had no better survival compared to patients with no downstaging. Patients with involved subcarinal nodes at mediastinoscopy and patients with involvement of more than one level had a worse survival. CONCLUSION: Surgery in N2-patients responsive to induction chemotherapy resulted in a high complete resectability rate. Findings at pre-treatment mediastinoscopy proved to be the most important prognostic factor.

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