Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Perspectives of nursing home executives on collaboration with GPs and specialist palliative care teams.

Background: Nursing home (NH) staff, general practitioners (GPs) and specialist outpatient palliative care teams are expected to cooperate to ensure adequate palliative care for NH residents in Germany. Aim: The aim of this study was to investigate the perspective of NH executives concerning collaboration with GPs and specialist outpatient palliative care teams. Methods: We conducted semi-structured telephone interviews with executives of NHs in the federal state of Baden-Wuerttemberg, Germany. Interviews were analysed by means of structured content analyses. Results: Executives of 20 NHs participated in the study, eight NHs cooperate with specialist outpatient palliative care teams. Content analysis resulted in two main categories: 'general palliative care by primary carers' and 'collaboration with SAPV in NHs', each with three first-order subcategories. The main barriers to adequate palliative care were reported to be lack of palliative care knowledge in GPs and NH staff, refusal of some GPs to cooperate with specialist outpatient palliative care teams and staff shortage in NHs. Specialist palliative care involvement was described to result in improved palliative care. Conclusion: Solutions seem obvious, e.g., further education in palliative care or round tables to discuss collaboration. However, studies show that even comprehensive educational and management interventions to implement palliative care do not always result in long-term effects and further research is needed.

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. METHODS AND MATERIALS: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. RESULTS: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. CONCLUSIONS: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.

Ultrasound-based repositioning and real-time monitoring for abdominal SBRT in DIBH.

AIM: Ultrasound-based repositioning and real-time-monitoring aim at the improvement of the precision of SBRT in deep inspiration breath-hold (DIBH). Accuracy of ultrasound-based daily repositioning was estimated by comparison with DIBH-cone-beam-CT. Intrafraction motion during beam-delivery was assessed by ultrasound-real-time-monitoring. PATIENTS/METHODS: Residual error after ultrasound-based interfractional repositioning (85 fractions, 16 SBRT-series; 14 patients) was assessed by marker-based (7 series) or liver-contour-based (9 series) matching in DIBH-CBCT. During beam-delivery, the percentage of 3D misalignment vector below 2 mm, between 2 and 5 mm, 5-7 mm and over 7 mm was estimated. Percentage of relevant target-displacements was analyzed as a function of DIBH-duration. RESULTS: Residual error after ultrasound-based positioning was 0.4 ±â€¯3.3 mm in LR (left-right), 0.2 ±â€¯4.3 mm in CC (cranio-caudal) and 1.0 ±â€¯3.0 mm in AP (anterior-posterior) directions (vector magnitude 5.4 ±â€¯3.3 mm, MV ±â€¯SD). Over 544 DIBHs, target displacement was 1.3 ±â€¯0.5 mm, 0.7 ±â€¯0.3 mm, 1.6 ±â€¯0.6 mm for CC, LR and AP directions, respectively (3D-vector 2.5 ±â€¯0.7 mm). 3D misalignment vector length was below 2 mm in 49.8%, between 2 and 7 mm in 46.3%, and over 7 mm in 3.9% of the beam-delivery-time. During the first 5 s of the DIBH, 3D-misalignment vector length was always below 10 mm. Percentage of target displacements over 10 mm was 0.2%, 0.5% and 0.8% for 10 s, 15 s and 20 s DIBH-duration. CONCLUSIONS: Ultrasound-based interfractional repositioning is an accurate method for daily localization of abdominal DIBH-SBRT targets. Residual motion is <7 mm in 96% of the beam-delivery-time. Deviations >10 mm occur rarely and can be avoided by gating the beam at a predefined threshold. Ideal DIBH-duration should not exceed 15 s.

Intra-breath-hold residual motion of image-guided DIBH liver-SBRT: An estimation by ultrasound-based monitoring correlated with diaphragm position in CBCT.

BACKGROUND AND PURPOSE: Craniocaudal motion during image-guided abdominal SBRT can be reduced by computer-controlled deep-inspiratory-breath-hold (DIBH). However, a residual motion can occur in the DIBH-phases which can only be detected with intrafractional real-time-monitoring. We assessed the intra-breath-hold residual motion of DIBH and compared residual motion of target structures during DIBH detected by ultrasound (US). US data were compared with residual motion of the diaphragm-dome (DD) detected in the DIBH-CBCT-projections. PATIENTS AND METHODS: US-based monitoring was performed with an experimental US-system simultaneously to DIBH-CBCT acquisition. A total of 706 DIBHs during SBRT-treatments of metastatic lesions (liver, spleen, adrenal) of various primaries were registered in 13 patients. Residual motion of the target structure was documented with US during each DIBH. Motion of the DD was determined by comparison to a reference phantom-scan taking the individual geometrical setting at a given projection angle into account. Residual motion data detected by US were correlated to those of the DD (DIBH-CBCT-projection). RESULTS: US-based monitoring could be performed in all cases and was well tolerated by all patients. Additional time for daily US-based setup required 8 ±â€¯4 min. 385 DIBHs of 706 could be analyzed. In 59% of all DIBHs, residual motion was below 2 mm. In 36%, residual motion of 2-5 mm and in 4% of 5-8 mm was observed. Only 1% of all DIBHs and 0.16% of all readings revealed a residual motion of >8 mm during DIBH. For DIBHs with a residual motion over 2 mm, 137 of 156 CBCT-to-US curves had a parallel residual motion and showed a statistical correlation. DISCUSSION AND CONCLUSION: Soft-tissue monitoring with ultrasound is a fast real-time method without additional radiation exposure. Computer-controlled DIBH has a residual motion of <5 mm in >95% which is in line with the published intra-breath-hold-precision. Larger intrafractional deviations can be avoided if the beam is stopped at an US-defined threshold.

An offline technique to evaluate residual motion of the diaphragm during deep inspiratory breath-hold from cone-beam CT datasets.

PURPOSE: In radiation therapy, the computer-assisted deep inspiration breath-hold (DIBH) technique is one approach to deal with respiratory motion of tumors in the lung, liver, or upper abdomen. However, inter- and intra-breath-hold deviations from an optimal static tumor position might occur. A novel method is presented to noninvasively measure the diaphragm position and thus estimate its residual deviation (as surrogate for the tumor position) based on cone-beam computed tomography (CBCT) projection data using active breathing control during acquisition. METHODS: The diaphragm dome (DD) position relative to the isocenter of a linear accelerator is known from the static (DIBH) planning CT. A ball-bearing phantom (BB) is placed at this position, a CBCT dataset is acquired, and in each projection the position of the projected BB is determined automatically based on thresholding. The position of the DD is determined manually in CBCT projections of a patient. The distance between DD and BB (ideal static setting) in craniocaudal direction is calculated for a given angle based on the distance in the projection plane and the relative position of the BB referring to the source and the detector. An angle-dependent correction factor is introduced which takes this geometrical setting into account. The accuracy of the method is assessed. RESULTS: The method allows a CBCT projection-based estimation of the deviation between the DD and its optimal position as defined in the planning CT, i.e., the residual motion of the DD can be assessed. The error of this estimation is 2.2 mm in craniocaudal direction. CONCLUSIONS: The developed method allows an offline estimation of the inspiration depth (inter- and intra-breath-hold) over time. It will be useful as a reference for comparison to other methods of residual motion estimation, e.g., surface scanning.

A 4D ultrasound real-time tracking system for external beam radiotherapy of upper abdominal lesions under breath-hold.

BACKGROUND AND PURPOSE: To evaluate a novel four-dimensional (4D) ultrasound (US) tracking system for external beam radiotherapy of upper abdominal lesions under computer-controlled deep-inspiration breath-hold (DIBH). MATERIALS AND METHODS: The tracking accuracy of the research 4D US system was evaluated using two motion phantoms programmed with sinusoidal and breathing patterns to simulate free breathing and DIBH. Clinical performance was evaluated with five healthy volunteers. US datasets were acquired in computer-controlled DIBH with varying angular scanning angles. Tracked structures were renal pelvis (spherical structure) and portal/liver vein branches (non-spherical structure). An external marker was attached to the surface of both phantoms and volunteers as a secondary object to be tracked by an infrared camera for comparison. RESULTS: Phantom measurements showed increased accuracy of US tracking with decreasing scanning range/increasing scanning frequency. The probability of lost tracking was higher for small scanning ranges (43.09% for 10° and 13.54% for 20°).The tracking success rates in healthy volunteers during DIBH were 93.24 and 89.86% for renal pelvis and portal vein branches, respectively. There was a strong correlation between marker motion and US tracking for the majority of analyzed breath-holds: 84.06 and 88.41% of renal pelvis target results and 82.26 and 91.94% of liver vein target results in anteroposterior and superoinferior directions, respectively; Pearson's correlation coefficient was between 0.71 and 0.99. CONCLUSION: The US system showed a good tracking performance in 4D motion phantoms. The tracking capability of surrogate structures for upper abdominal lesions in DIBH fulfills clinical requirements. Further investigation in a larger cohort of patients is underway.

MRI morphologic alterations after liver SBRT : Direct dose correlation with intermodal matching.

AIM: CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. PATIENTS AND METHODS: MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD2,α/ß =x with α/ß values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. RESULTS: A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD2Gy/α/ß =10 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD2Gy/α/ß =10 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD2,α/ß =2 42.5 ± 8.7 Gy, EQD2,α/ß =3 38.5 ± 7.6 Gy, EQD2,α/ß =8 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD2,α/ß=2 42.7 ± 8.1 Gy, EQD2,α/ß=3 38.7 ± 7 Gy; EQD2,α/ß=8 30.5 ± 5.9 Gy). CONCLUSIONS: Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD2,α/ß =2-3) induce characteristic MRI morphologic alterations.

Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review.

Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.