Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer.

PURPOSE: Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. METHODS: Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. RESULTS: Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. CONCLUSION: FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.

Intrafractional dose variation and beam configuration in carbon ion radiotherapy for esophageal cancer.

BACKGROUND: In carbon ion radiotherapy (CIR) for esophageal cancer, organ and target motion is a major challenge for treatment planning due to potential range deviations. This study intends to analyze the impact of intrafractional variations on dosimetric parameters and to identify favourable settings for robust treatment plans. METHODS: We contoured esophageal boost volumes in different organ localizations for four patients and calculated CIR-plans with 13 different beam geometries on a free-breathing CT. Forward calculation of these plans was performed on 4D-CT datasets representing seven different phases of the breathing cycle. Plan quality was assessed for each patient and beam configuration. RESULTS: Target volume coverage was adequate for all settings in the baseline CIR-plans (V95 > 98% for two-beam geometries, > 94% for one-beam geometries), but reduced on 4D-CT plans (V95 range 50-95%). Sparing of the organs at risk (OAR) was adequate, but range deviations during the breathing cycle partly caused critical, maximum doses to spinal cord up to 3.5x higher than expected. There was at least one beam configuration for each patient with appropriate plan quality. CONCLUSIONS: Despite intrafractional motion, CIR for esophageal cancer is possible with robust treatment plans when an individually optimized beam setup is selected depending on tumor size and localization.

The effect of real-time electronic monitoring of patient-reported symptoms and clinical syndromes in outpatient workflow of medical oncologists: E-MOSAIC, a multicenter cluster-randomized phase III study (SAKK 95/06).

BACKGROUND: Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes. PATIENTS AND METHODS: In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient-oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients. RESULTS: In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit-BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse-patient interview) by oncologists getting the LoMoS. CONCLUSION: Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial.

BACKGROUND: In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. METHODS/DESIGN: The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

Detection of gastric MALT lymphoma spreading to the small bowel by enteroscopy.

Mucosa-associated lymphoid tissue (MALT) lymphoma is thought to be a multifocal disease with sometimes synchronous involvement of various mucosal structures. In this study we aimed to evaluate the potential involvement of the small bowel in patients suffering from gastric MALT lymphoma by analyzing the results of enteroscopy, a technique that allows easy and safe access to the small bowel with the potential for histological assessment of biopsy samples. We have retrospectively evaluated 347 enteroscopies and found nine patients with gastric MALT lymphoma who had undergone push enteroscopy with serial biopsies during staging. All patients tolerated enteroscopy without side effects, and no local complications occurred. In eight cases no evidence of duodenal or jejunal involvement was found macroscopically or by histological assessment of biopsies, while in one patient enteroscopy revealed jejunal MALT lymphoma infiltration with macroscopic accentuation of mucosal parts and consecutive histopathological verification more distal than 50 cm. This single-center retrospective analysis shows that enteroscopy can provide additional diagnostic information in patients with gastric MALT lymphoma, although the number of patients was small and only one out of nine patients showed hitherto undetected MALT lymphoma deposits. Further studies may quantify the additional diagnostic yield provided by this easy and safe endoscopic method.

Diagnostic cholangiopancreatography.

As in recent years, the articles on diagnostic endoscopic retrograde cholangiopancreatography (ERCP) published between July 2001 and June 2002 again reflect a defensive attitude and are mainly concerned with magnetic resonance cholangiopancreatography (MRCP) and the complications associated with the new imaging method. Diagnostic ERCP is declining in importance and has held its position mainly due to new advances in tissue sampling, pressure measurement, and the use of echo probes and miniature endoscopes. Problems of training in ERCP have still not yet been resolved, due to the contradictions inherent in low case loads, the desire to offer a wide spectrum of training, and issues of quality assurance.

Evaluation of a virtual endoscopy simulator for training in gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: Skills in gastrointestinal endoscopy mainly depend on experience and practice. Training on endoscopy simulators may decrease the time needed to reach competency in endoscopy. The purpose of the study was to determine whether the GI-Mentor, a virtual reality endoscopy simulator, can distinguish between beginners and experts in endoscopy and to assess whether training improves the performance of beginners. METHODS: A total of 13 beginners and 11 experts (more than 1,000 procedures) in gastrointestinal endoscopy were included. The baseline assessment consisted of virtual endoscopies and skill tests. The beginners were randomly allocated to receive training (n = 7) or no training (n = 6). The training group was allowed to practice using the simulator for 2 hours per day. After 3 weeks participants were re-evaluated with two new virtual endoscopy cases and one virtual skill test. Insertion time, correctly identified pathologies, adverse events and skill test performance were recorded. RESULTS: The baseline assessment revealed significant differences favoring the experts for virtual endoscopies and skill tests. Significant differences in favor of experts were found for successful retroflection during esophagogastroduodenoscopy (EGD) (P < 0.005); adverse events during colonoscopy (P < 0.02); insertion time (P < 0.001); correctly identified pathologies in gastroscopy and colonoscopy (P < 0.02); and skill test performance (P < 0.01). The final evaluation showed significant differences between training and no-training groups, in favor of the training group, for the number of adverse events during virtual endoscopy (P < 0.04), for the insertion time during colonoscopy (P < 0.03); and for skill test performance (P < 0.01). The training group improved its abilities on the simulator significantly. Differences between experts and the training group were no longer seen. CONCLUSION: This virtual endoscopy simulator is capable of identifying differences between beginners and experts in gastrointestinal endoscopy. A 3-week training improves the performance of beginners significantly. This quite fast improvement in endoscopic skills certainly cannot be seen in clinical practice; no conclusions can be made about the impact of virtual simulator training on real-life endoscopy, and this must be evaluated.

Forceps biopsy and brush cytology during endoscopic retrograde cholangiopancreatography for the diagnosis of biliary stenoses.

BACKGROUND: For evaluating pancreaticobiliary stenoses during endoscopic retrograde cholangiopancreatography (ERCP) tissue sampling techniques may be important. Brush cytology and forceps biopsy during ERCP are two potential, but so far only incompletely evaluated, tools for the diagnosis of malignant biliary or pancreatic stenoses. METHODS: Between 1992 and 1995 we acquired 133 cytologic and/or histologic samples from 119 patients who underwent ERCP because of biliary duct stenoses. Sixteen patients had to be excluded from the study due to insufficient follow-up information. After papillotomy, brush cytology was performed in 65 cases (63 patients), and forceps biopsy in 119 cases (106 patients under fluoroscopic guidance. Both methods were applied in combination 51 times (48 patients). The nature of the stenoses was confirmed by surgery, autopsy, or by the subsequent clinical course. RESULTS: The sensitivity was 46.7% for brush cytology and 64.9% for forceps biopsy. The combined application of both methods resulted in superior sensitivity (70.4%). Specificity was 100% for all methods. CONCLUSIONS: These numbers lead us to recommend a combined and more frequent application of brush cytology and forceps biopsy of bile duct stenoses to enhance the diagnostic yield whenever substantial influence on therapy can be expected.

Two cases of fractured esophageal nitinol stents.

We report here on two cases of fractured nitinol stents in the esophagus. In case 1, the correctly inserted stent broke spontaneously shortly after insertion. In a second case, a nitinol stent broke after laser application due to tumor ingrowth with massive bleeding. In both cases, a second stent was implanted in order to reestablish food passage. The fracture of the stent in case 1 seemed to be caused by defective material, whilst in case 2 the stent broke because of thermal overstrain during laser application. The use of electrocoagulation or laser in the stent area should therefore be avoided; argon plasma coagulation may offer an effective alternative in treating tumor ingrowth. As there was a risk from piercing broken filaments with the second stent, covering a fracture using stents with tight walls or plastic tubes seems to be a more effective approach than the inserting an uncovered stent type.