Walter De Wever

The impact of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer

Abstract Purpose : 18 F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) combined with computer tomography (PET-CT) is superior to CT alone in mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). We studied the potential impact of this non-invasive LN staging procedure on the radiation treatment plan of patients with NSCLC. Patients and methods : The imaging and surgical pathology data from 105 patients included in two previously published prospective LN staging protocols form the basis for the present analysis. For 73 of these patients, with positive LNs on CT and/or on PET, a theoretical study was performed in which for each patient the gross tumour volume (GTV) was defined based on CT and on PET-CT data. For each GTV, the completeness of tumour coverage was assessed, using the available surgical pathology data as gold standard. A more detailed analysis was done for the first ten consecutive patients in whom the PET-CT-GTV was smaller than the CT-GTV. Theoretical radiation treatment plans were constructed based on both CT-GTV and PET-CT-GTV. Dose-volume histograms for the planning target volume (PTV), for the total lung volume and the lung volume receiving more than 20 Gy ( V lung(20) ), were calculated. Results : Data from 988 assessed LN stations were available. In the subgroup of 73 patients with CT or PET positive LNs, tumour coverage improved from 75% when the CT-GTV was used to 89% with the PET-CT-GTV ( P =0.005). In 45 patients (62%) the information obtained from PET would have led to a change of the treatment volumes. For the ten patients in the dosimetry study, the use of PET-CT to define the GTV, resulted in an average reduction of the PTV by 29±18% (±1 SD) ( P =0.002) and of the V lung(20) of 27±18% (±1 SD) ( P =0.001). Conclusion : In patients with NSCLC considered for curative radiation treatment, assessment of locoregional LN tumour extension by PET will improve tumour coverage, and in selected patients, will reduce the volume of normal tissues irradiated, and thus toxicity. This subgroup of patients could then become candidates for treatment intensification.

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction : a prospective study based on primary surgery with extensive lymphadenectomy

ObjectiveTo 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 DataFDG-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. MethodsForty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET 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). ResultsThe 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 FDG-PET 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. ConclusionsFDG-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.

Prospective Comparative Study of Integrated Positron Emission Tomography-Computed Tomography Scan Compared With Remediastinoscopy in the Assessment of Residual Mediastinal Lymph Node Disease After Induction Chemotherapy for Mediastinoscopy-Proven Stage IIIA-N2 Non–Small-Cell Lung Cancer: A Leuven Lung Cancer Group Study

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 non-small-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.

FDG-PET scan in potentially operable non-small cell lung cancer : Do anatometabolic PET-CT fusion images improve the localisation of regional lymph node metastases?

Abstract Exact localisation of thoracic lymph nodes (LNs) on fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) can be hampered by the paucity of anatomical landmarks. In non-small cell lung cancer (NSCLC) patients referred for locoregional LN staging, we prospectively examined to what extent localisation of LNs at PET reading could be improved by visual correlation with computed tomography (CT), or by anatometabolic PET+CT fusion images. Fifty-six patients with potentially operable NSCLC underwent CT, PET and surgical staging. Prospective reading was performed for CT, PET without CT, PET+CT visual correlation and PET+CT fusion. Reading was blinded to surgical pathology data and noted on a standard LN map. Surgical staging was available for 493 LN stations. In the evaluation per individual LN station, CT was accurate in 87%, PET in 91% and visual correlation and fusion in 93%. In the identification of the nodal stage, CT was correct in 28/56 patients (50%), PET in 37/56 (66%), visual correlation in 40/56 (71%), and fusion in 41/56 (73%). It is concluded that in the exact localisation of metastatic thoracic LNs, the accuracy of reading of PET is increased if the PET images can be visually correlated with CT images. PET+CT anatometabolic fusion images add only a marginal benefit compared with visual correlation.

Survival determinants in lung transplant patients with chronic allograft dysfunction.

Background. Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality after lung transplantation. Methods. In this retrospective single-center study, we aimed to identify different phenotypes of and risk factors for mortality after CLAD diagnosis using univariate and multivariate Cox proportional hazard survival regression analysis. Results. CLAD was diagnosed in 71 of 294 patients (24.2%) at 30.9±22.8 months after transplantation. Pulmonary function was obstructive in 51 (71.8%) of the CLAD patients, restrictive in 20 (28.2%) patients, of whom 17 had persistent parenchymal infiltrates on pulmonary computer tomography (CAT) scan. In univariate analysis, previous development of neutrophilic reversible allograft dysfunction (NRAD, P=0.012) and a restrictive pulmonary function (P=0.0024) were associated with a worse survival, whereas there was a strong trend for early development of CLAD and persistent parenchymal infiltrates on CAT scan (P=0.067 and 0.056, respectively). In multivariate analysis, early development of CLAD (P=0.0067), previous development of NRAD (P=0.0016), and a restrictive pulmonary function pattern (P=0.0005) or persistent parenchymal infiltrates on CAT scan (P=0.0043) remained significant. Conclusion. Although most CLAD patients develop an obstructive pulmonary function, 28% develop a restrictive pulmonary function, compatible with the recently defined restrictive allograft syndrome phenotype. Early-onset CLAD, previous development of NRAD, and the development of restrictive allograft syndrome are associated with worse survival after CLAD has been diagnosed.

Additional value of PET-CT in staging of clinical stage IIB and III breast cancer.

Abstract:  To evaluate retrospectively the accuracy of integrated PET/CT, against PET, CT, or conventional staging in breast cancer. Seventy consecutive biopsy proven clinical stage IIB and III breast cancer patients were included. Descriptive statistics of integrated PET/CT for the primary tumor, nodal status and metastasis detection were compared to PET, CT with contrast, and conventional staging (biochemistry, chest X‐ray, liver ultrasound, and bone scintigraphy). Sensitivity of PET/CT for primary tumor and nodal status was 97.1% and 62.5%, respectively. Specificity and negative predictive value for nodal status were 100% and 66.6%, respectively. The values for conventional staging for nodal involvement were 100% and 85.7% with a sensitivity of 87.5%. PET/CT showed metastatic disease in seven women despite normal conventional staging. PET/CT is able to visualize most clinical stage IIB and III primary breast cancers. PET/CT is superior to conventional staging for detecting internal mammary chain nodes and metastatic disease, but not for axillary staging. Future studies will have to test whether therapy adjustment based on PET/CT has the potential to improve survival.

Hodgkin lymphoma: Response assessment by Revised International Workshop Criteria

Until recently, response assessment in patients with Hodgkins lymphoma (HL) was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose positron emission tomography (FDG-PET) has a higher sensitivity and specificity compared with that of CT, and Revised International Workshop Criteria (IWC + PET) were recently proposed, which combine both imaging techniques. We determined whether these integrated IWC + PET-criteria can more accurately predict outcome compared with IWC-criteria in 56 patients with HL. Of the original 56 patients, nine patients relapsed and 47 are still in remission after a median follow-up of 9 years. Based on IWC-criteria, 15 patients had a complete remission (CR) after chemotherapy, 20 had complete remission unconfirmed (CRu), 19 had partial remission (PR) and two had stable disease (SD). In comparison, by IWC + PET, 47 had CR, seven had PR and two had SD. For IWC, outcome was not significantly different in patients with CR/CRu compared to PR (P = 0.61), while for IWC + PET criteria, time-to-next-treatment was significantly shorter in patients with PR compared to CR (P = 0.01). Therefore, IWC + PET-guidelines provide a more accurate response classification compared with that of IWC-guidelines, and are the preferred method for response assessment in patients with Hodgkins lymphoma.

Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma

Introduction: Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. Methods: Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tomography scans were collected at diagnosis and, when possible, during and after therapy. For each patient, the best overall radiological response was compared with the changes in serum SM, MPF, and plasma OPN levels across corresponding time points. Results: In five patients, blood sampling was done shortly before and after extrapleural pneumonectomy. SM and MPF levels markedly decreased after surgery, whereas OPN levels showed a median increase. Fifty-seven patients were surveilled during (and after) chemotherapy, of whom 27 (47%) had stable disease, 14 (25%) partial response, and 16 (28%) progressive disease. In patients with stable disease, SM and MPF levels did not change significantly across the corresponding time points, whereas OPN levels significantly decreased. In those with partial response, SM and MPF levels significantly decreased, whereas OPN levels showed no significant change. In patients with progressive disease, all three biomarker levels significantly increased. Patient responses correlated with a 15% change in all three biomarkers, although SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable progression-free survival and overall survival. Neither SM nor MPF showed prognostic value. Conclusions: SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.

The Respiratory Tract

Airways may be affected by a variety of diseases. Diseases of the large airways can result from abnormalities of the wall (intrinsic abnormalities) or from compression from adjacent structures (extrinsic abnormalities). Intrinsic abnormalities are classified as either focal or diffuse, depending on the extent of involvement of the airways. The diffuse abnormalities are less common and usually benign, most of the time caused by autoimmune illnesses or multisystem disorders. Focal abnormalities include tumors, infections, granulomatous diseases, and iatrogenic disorders. Focal disease tends to produce decreased airway diameter. The diffuse diseases may be divided into those that increase the diameter and those that decrease the diameter of the airway. Plain chest radiography remains a convenient first-line investigation for any patient who presents with respiratory symptoms and signs. The air within the trachea and main bronchi gives good, inherent radiographic contrast. Well-penetrated films may demonstrate tracheobronchial pathology: however, abnormalities of the major airways can easily be missed on radiographs. Computed Tomography (CT) has been shown to be superior to conventional radiography in the detection of abnormalities of the airways. The axial CT images are primarily used for diagnostic purposes. Two-dimensional and three-dimensional reformatted images offer a number of advantages, such as a better assessment of the craniocaudal extent of disease and the ability to detect subtle airway stenoses.

Intensity-Modulated Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer: A Dose-Escalation Planning Study

PURPOSE To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). METHODS AND MATERIALS For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). RESULTS IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. CONCLUSION In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.