P. De Leyn

Utility of Positron Emission Tomography for the Staging of Patients With Potentially Operable Esophageal Carcinoma

PURPOSE A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma

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.

Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy.

From 1975 through 1988, 257 patients with carcinoma of the thoracic esophagus have been treated in our department. Operability was 90% (232/257); overall resectability, 77% (198/257), and for the operated group, 85% (198/232). Hospital mortality rate was 9.6% but decreased to 3% over the period 1986 to 1988. There were 65% squamous cell epitheliomas and 35% adenocarcinomas. Tumor, nodes, and metastases (pTNM) staging was as follows: stage I, 11.6%; stage II, 23.2%; stage III, 37.9%; stage IV, 27.3%. Overall survival rate was 62.5% at 1 year, 42.4% at 2 years, and 30% at 5 years. According to the pTNM staging, 5-year survival was 90% for stage I, 56% for stage II, 15.3% for stage III, and 0 for stage IV. There were no statistically significant differences according to tumor localization, pathologic type, sex, or age. Introducing extensive resection and extended lymphadenectomy seems to improve significantly survival in patients in whom an operation with curative intention was performed, the 1 year survival rate being 90.8% versus 72%; 2-year survival, 81% versus 46%; and 5-year survival, 48.5% versus 41% for radical and nonradical resections, respectively. Based on multivariate Cox regression analysis, only TNM stage and presence or absence of lymph nodes are important factors in predicting survival: stage 1 tumors have lower risk, and involvement of lymph nodes creates higher risk. Using this analysis, there was only for the patients with involved lymph nodes (N1) a significantly better prognosis when a radical lymph node dissection was performed (p = 0.0055). Barrett adenocarcinomas have no worse prognosis than other esophageal carcinomas, with a 5-year survival rate of 91.5% if lymph nodes are negative, and a 54% overall 5-year survival rate. Functional results after restoration of continuity with gastric tubulation were judged excellent to very good in 86.5% at 1 year, but infra-aortic anastomoses have a much higher incidence of peptic esophagitis: 53% versus 8% for cervical anastomoses. From this study it can be concluded that in experienced hands surgery today offers the best chances for optimal staging, potential cure, and prolonged high-quality palliation.

Tumors of the esophagogastric junction: long-term survival in relation to the pattern of lymph node metastasis and a critical analysis of the accuracy or inaccuracy of ptnm classification

From 1983 to 1989, 95 patients with carcinoma of the esophagogastric junction underwent resection. Overall hospital mortality rate was 6.2% (6/95). Actuarial survival analysis showed 5- and 10-year survivals of 33% and 31%, respectively. Five- and 10-year survivals of patients according to TNM stages were as follows: stage I (n = 13), 90% at both 5 and 10 years; stage II (n = 13), 70% at both intervals; stage III (n = 28), 28% at both intervals; and stage IV (n = 40), 11% and 8%, respectively. For patients with undiseased nodes (n = 26), 5- and 10-year survivals were 72% and 72%, compared with 18% and 16% for patients with diseased nodes (n = 68; p < 0.005). In patients who had involvement of both the abdominal and thoracic lymph nodes (n = 28), 5- and 10-year survivals were 13% and 13%, compared with 26% and 26% if metastases were confined to the abdomen (n = 37; p > 0.05). Grouping patients with diseased intrathoracic nodes together with patients with N2 abdominal nodes showed survivals of 14% at both 5 and 10 years. When tumors were staged as an esophageal carcinoma, classification of individual patients changed, as did the 5- and 10-year survivals. Five- and 10-year survivals were as follows: stage I (n = 8), 100% for both 5 and 10 years; stage II (n = 18), 68% for both 5 and 10 years; stage III (n = 27), 37% for both 5 and 10 years; and stage IV (n = 41), 10% for 5 years and 6% for 10 years. These data indicate that tumors of the esophagogastric junction tend to spread to both abdominal and thoracic nodes. However, reasonably good 5- and 10-year survivals can be obtained even in patients with nodal metastases in both areas. We suggest that N2 labeling be included for thoracic node metastases instead of the actual M+Ly label, because the N2 label better reflects the potential for curative surgery. Finally, staging tumors as gastric or esophageal carcinoma makes no significant difference in survival analysis, which raises the question whether these tumors behave more like esophageal carcinoma than gastric carcinoma.

Potential use of FDG-PET scan after induction chemotherapy in surgically staged IIIa–N2 non-small-cell lung cancer: A prospective pilot study

BACKGROUND Clearance of viable tumour cells in mediastinal lymph nodes (MLN) by induction chemotherapy (IC)--so-called MLN downstaging--is an important aspect of combined-modality treatment of N2-NSCLC. Reassessment of MLN after IC by CT is far from accurate, while re-mediastinoscopy is often technically difficult. Based on our previous results with FDG-PET in the initial staging of N2 disease, we investigated whether PET after IC could be helpful in predicting MLN downstaging and therapeutic outcome. PATIENTS AND METHODS Patients underwent a first PET before IC. After three cycles of platinum-based IC, a second PET was performed before locoregional therapy, either surgery or radiotherapy. PET results were correlated with pathology of the MLN when available, and with survival. RESULTS Fifteen surgically staged N2-NSCLC patients were prospectively included. Locoregional therapy after IC consisted of surgery in nine and radiotherapy in six. Correlation with pathology of the nine resection specimens revealed that the accuracy of PET in predicting MLN downstaging was 100% (six true negatives; three true positives), whereas for CT it was only 67% (two false pos; one false neg). Reassessment with PET after IC was correlated with the outcome after the entire combined modality treatment. Survival was significantly better in patients with mediastinal clearance (P = 0.01) or with a greater than 50% decrease in the Standardised Uptake Value (SUV) of the primary tumour (P = 0.03) after IC. CONCLUSIONS Mediastinal PET after IC accurately assesses pathologic MLN downstaging in N2-NSCLC. The data suggest a possible correlation of early survival with mediastinal clearance and an important decrease of SUV in the primary tumour. Confirmation of these preliminary findings would establish PET as a useful non-invasive tool to select patients for intensive locoregional treatment after IC.

Anastomotic complications after esophagectomy.

Anastomotic complications after esophagectomy continue to be a burden jeopardizing the quality of life and of swallowing. However, incidence, mortality and morbidity of anastomotic complications have substantially decreased in recent years. It seems that this is not so much related to the use of a particular conduit, approach or route for reconstruction, but rather related to refinement in anastomotic techniques and perhaps even more to progress in modern perioperative management. Knowledge of surgical anatomy and meticulous technique are of paramount importance and obviously related to individual expertise. As to the management, most leaks can be treated by conservative measures and reintervention surgery today is rather exceptional. Early endoscopy and dilatation seem to decrease the incidence and severity of anastomotic stenosis.

Surgical treatment of Barrett's carcinoma: Correlations between morphologic findings and prognosis

Barretts carcinoma occurred in 66 of 331 patients with adenocarcinomas of the esophagus or gastroesophageal junction. Only 32 (46 %) of these patients had a history of gastroesophageal reflux. A history of alcohol and tobacco abuse was absent in 50 % and 47.5 %, respectively. The mean length of Barretts metaplasia was 7.37 cm. Operability was 98.5 % and resectability 95.5 %. No postoperative or hospital deaths occurred. Pathologic staging was as follows: stage 0 and I, 38.3 %; stage 11, 20.6 %; stage 111, 22.2 % ; and stage IV, 19 %. Overall survivals were 80.5 % at 1 year, 62.7 % at 2 years, and 58.2% at 5 years. Five-year survival for patients with stage I disease was 100%; for stage II, 87.5%; for stage III, 22.2 %; and for stage IV, 0 %. Thirty-four (51.5 %) patients were under surveillance for a related or unrelated condition before diagnosis of their carcinoma; only nine (26.5 %) had diseased lymph nodes. In 32 the diagnosis was made at their first medical contact, and 78 % of them had diseased lymph nodes. Five-year survival without nodal metastasis was 85.3 % and significantly better than for patients with metastasis, 38.3 % (p = 0.0033). Of the 66 patients, 19 (28.7 %) had a biopsyproved history of Barretts metaplasia before malignancy developed. Mean time interval between diagnosis of metaplasia and degeneration was 3.8 years (89.5 %>1 year). Over the surveillance period, the length of metaplastic Barretts esophagus remained unchanged in all patients. Barretts ulceration was present from the beginning in 14 patients, and three patients never had an ulcer. Intestinal metaplasia was seen in 18 patients. Resected specimens revealed severe dysplasia in 16 patients. Of the 19 patients, 73.7 % had stage I disease. Our data suggest that close endoscopic monitoring and systematic biopsies of the smallest irregularities in the metaplastic mucosa may result in early detection of carcinoma. In this respect, patients with an ulcer within a zone of intestinal metaplasia seem to be at risk. Early detection increases substantially the chances for cure by diminishing the risks of lymph node involvement. Resection remains the treatment of choice in Barretts adenocarcinoma including high-grade dysplasia, because mortality can be kept low with excellent to very good functional results in the majority of the patients provided the intervention is performed by experienced teams.

2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan

OBJECTIVE The results of primary surgery for non-small cell lung cancer (NSCLC) with involved ipsilateral mediastinal or subcarinal lymph nodes (N2 disease) remains poor. However, several studies suggest that induction chemotherapy could increase long-term survival in patients with N2 disease. Therefore, accurate preoperative staging of the mediastinum remains of paramount importance for the treatment policy in patients with NSCLC. Enlarged mediastinal lymph nodes (MLN) on CT scan are positive in only half of the patients. Small lymph nodes can contain metastatic deposits of clinical importance. However, many surgeons believe that a normal mediastinum at computed tomography allows them to cancel their preoperative mediastinal exploration. It was the aim of this study to evaluate the results of cervical mediastinoscopy in patients without enlarged MLN on CT scan. METHODS Between January 1990 and June 1994, 235 patients with potentially operable NSCLC underwent a cervical mediastinoscopy despite the absence of enlarged MLN on CT scan. MLN were considered enlarged if they were equal to or larger than 15 mm at their maximal cross-sectional diameter. RESULTS Cervical mediastinoscopy was positive in 47 patients (20%). In 21 patients, N2 disease was extranodal and in 16 patients more than one level was involved. Mediastinoscopy was positive in 9.5% of the cT1N0 cases, in 17.7% of the cT2N0 lesions, in 31.2 and 33.3% of cT3N0 or cT4N0 tumors, respectively. After a negative cervical mediastinoscopy, resectability for unforeseen N2 disease was as high as 95%. CONCLUSION We recommend a cervical mediastinoscopy in every patient with potentially operable NSCLC.