Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

OBJECTIVE: In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is a challenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. METHODS: Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. RESULTS: In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. CONCLUSION: Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. TRIAL REGISTRATION NUMBER AND DATE: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Ultrasonic bone cement removal efficiency in total joint arthroplasty revision: A computer tomographic-based cadaver study.

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix®). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 µm resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 ± 4.95 mm3 were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations.

Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer.

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

Utility of fiducial markers for target positioning in proton radiotherapy of oesophageal carcinoma.

BACKGROUND AND PURPOSE: Oesophageal mobility relative to bony anatomy is a major source of geometrical uncertainty in proton radiotherapy of oesophageal carcinoma. To mitigate this uncertainty we investigated the use of implanted fiducial markers for direct target verification in terms of safety, visibility, and stability. MATERIALS AND METHODS: A total of 19 helical gold markers were endoscopically implanted in ten patients. Their placement at the proximal and distal tumour borders was compared to tumour demarcations derived from [18F]Fluorodeoxyglucose positron emission tomography, their visibility quantified via the contrast-to-noise ratio on daily orthogonal X-ray imaging, and their mobility relative to bony anatomy analysed by means of retrospective triangulation. RESULTS: Marker implantation proceeded without complications, but the distal tumour border could not be reached in two patients. Marker locations corresponded reasonably well with metabolic tumour edges (mean: 5.4 mm more distally). Marker visibility was limited but mostly sufficient (mean contrast-to-noise ratio: 1.5), and sixteen markers (84%) remained in situ until the end of treatment. Overall, marker excursions from their planned position were larger than 5(10) mm in 59(17)% of all analysed fractions. On one occasion severe target displacement was only identified via markers and was corrected before treatment delivery. CONCLUSION: Implanted helical gold fiducial markers are a safe and reliable method of providing target-centric positioning verification in proton beam therapy of oesophageal carcinoma.

Molecular imaging using the theranostic agent 197(m)Hg: phantom measurements and Monte Carlo simulations.

BACKGROUND: Radiomercury 197mHg and 197Hg, henceforth referred to as 197(m)Hg, is a promising theranostic radionuclide endowed with properties that allow diagnostic and therapeutic applications. The aim of this work was to investigate the capabilities of 197(m)Hg for nuclear medicine imaging. Therefore measurements were performed by using a Philips BrightView SPECT camera. Furthermore, Monte Carlo simulations using the GATE software were performed to theoretically explore the imaging contribution from the various gamma and X-ray emissions from 197(m)Hg for a commercial clinical camera with low-energy high-resolution (LEHR) and high-energy general-purpose (HEGP) collimators. We estimated the spatial resolution by using a four-quadrant bar phantom, and we evaluated the planar and tomographic images from an abdominal phantom containing three cylindrical sources of 197(m)Hg solution. RESULTS: A good accordance between measurements and simulations was found for planar and SPECT imaging. Simulations allowed the decomposition of the detected energy spectrum into photon origins. Measurements and simulations for the bar phantom revealed that for the LEHR collimator, the 6-mm pattern could be resolved, whereas for the HEGP collimator, the resolution is about 10 mm. Furthermore, we found that no significant image distortion results from high-energy photons when using the LEHR collimator. CONCLUSIONS: We demonstrated the imaging capabilities of 197(m)Hg which is essential both for diagnostic applications and to determine the in vivo biodistribution for dose calculations in therapeutic applications.

The clinical target volume in lung, head-and-neck, and esophageal cancer: Lessons from pathological measurement and recurrence analysis.

Radiotherapy research has achieved remarkable progress in target volume definition. Advances in medical imaging facilitate more precise localization of the gross tumor volume, alongside a more detailed understanding of the geometric uncertainties associated with treatment delivery that has enabled robust safety margins to be customized to the specific treatment scenario at hand. By contrast, the clinical target volume, meant to encompass gross tumor, as well as, adjacent sub-clinical disease, has evolved very little. It is more often defined by clinician experience and institutional convention than on a patient-specific basis. This disparity arises from the inherent invisibility of sub-clinical disease in current medical imaging. Its incidence and expanse can only be ascertained via indirect means. This article reviews two such strategies: histopathological measurements on resection specimen and analyses of locoregional recurrences after radiotherapy.