US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers.

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor.Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy.Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community.Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.

Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU).

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20-50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.

Improvement of fibroid-associated symptoms and quality of life after US-guided high-intensity focused ultrasound (HIFU) of uterine fibroids.

Uterine fibroids are the most common benign uterine tumors and can cause various severe symptoms as abnormal menstrual bleeding or pelvic pain. Therefore, the primary objective in the treatment of uterine fibroids is a sufficient symptom relief. Ultrasound (US)-guided High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment strategy for ablation of uterine fibroids that can achieve a significant tumor volume reduction. The aim of the study is to evaluate if US-guided HIFU treatment can reduce fibroid-associated symptoms leading to an improvement of health-related quality of life. Fifty-five women with symptomatic uterine fibroids underwent US-guided HIFU ablation. Clinical evaluation was performed on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) at baseline, 6 weeks, 3, 6, 9 and 12 months after HIFU. Imaging follow-up included contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI. A significant reduction of the Symptom Severity Scale (SSS) was observed between 6 weeks and 12 months after HIFU (49.9 ± 19.4 at baseline vs. 42.2 ± 20.1 at 6 weeks and 23.6 ± 12.7 at 12 months after treatment, p < 0.001) correlating with a significant improvement (p < 0.001) of Health-related Quality of Life (HRQL) (52.5 ± 22.7 at baseline vs. 59.8 ± 22 at 6 weeks and 77.9 ± 17.3 at 12 months after treatment). Significant postinterventional improvement was observed in every subscale of HRQL. In the majority of patients, only minor, short-lasting and self-limiting side effects were observed, e.g. soft tissue edema of the anterior lower abdominal wall in the acoustic pathway or transient moderate lower abdominal pain as during menstruation. One patient with a very large fibroid experienced strong short-lasting pain after the procedure; two patients experienced post-procedurally a transient sciatic nerve irritation. US-guided HIFU of uterine fibroids reduces disease-related symptoms and improves health-related quality of life.

Predicting incomplete cytoreduction in patients with advanced ovarian cancer.

Purpose: The most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction. Methods: This is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher's exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction. Results: Complete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis. Conclusion: Large-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.

Multidisciplinary management to optimize outcome of ultrasound-guided high-intensity focused ultrasound (HIFU) in patients with uterine fibroids.

Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.

US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany.

INTRODUCTION: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.

Efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids: an observational single-center study.

INTRODUCTION: To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. MATERIALS AND METHODS: Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. RESULTS: In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. CONCLUSION: Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.

Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers.

OBJECTIVES: Pancreatic cancer patients often have a high symptom burden, significantly impairing patients' quality of life (QOL). Nevertheless, there are hardly any reports on the impact of high-intensity focused ultrasound (HIFU) on the QOL of treated patients. For the first time, this study evaluated the effect of HIFU on QOL and compared these results in two European centers. METHODS: Eighty patients with advanced pancreatic cancer underwent HIFU (50 in Germany, 30 in Bulgaria). Clinical assessment included evaluation of QOL and symptoms using the EORTC QLQ-C30 questionnaire at baseline and 1, 3, and 6 months after HIFU. Pain intensity was additionally evaluated with the numerical rating score (NRS). RESULTS: Compared to baseline, global health significantly improved 3 and 6 months after HIFU treatment (p = 0.02). Functional subscales including physical, emotional, and social functioning were considerably improved at 6 months (p = 0.02, p = 0.01, and p = 0.01, respectively) as were leading symptom pain (p = 0.04 at 6 months), fatigue (p = 0.03 at 3 and p = 0.01 at 6 months), and appetite loss (p = 0.01 at 6 months). Moreover, pain intensity measured by NRS revealed effective and strong pain relief at all time points (p < 0.001). Reported effects were independent of tumor stage, metastatic status, and country of treatment. CONCLUSIONS: This study showed that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL by increasing global health and mitigation of physical complaints with a low rate of side effects, independent of the examiner. Therefore, HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease. KEY POINTS: • In a prospective two-center study, it was shown that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL. • HIFU in pancreatic cancer patients is associated with a low rate of side effects, independent of the performer. • HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.

Multidisciplinary management and outcome in pancreatic cancer patients treated with high-intensity focused ultrasound.

Introduction: High-intensity focused ultrasound (HIFU) for pancreatic cancer is a growing therapeutic field which has been proven to reduce cancer pain and provide a local tumor control additionally to standard palliative care. However, less is known about the multidisciplinary and especially anesthesiological management of HIFU treatment although an interdisciplinary approach is crucial for treatment success.Material and methods: Anesthesiological and radiological records of 71 HIFU-treated pancreatic cancer patients were analyzed with regard to the following items: intervention time, sonication time, total energy, anesthesia time, peri-interventional medication, body temperature maximum and minimum, pain scores before and 1 day, 6 weeks and 3 months after intervention, peri-interventional complications. Effects on pain scores were estimated with a mixed panel data model. Bivariate associations between interventional variables were examined with the Spearman's correlation.Results: HIFU treatment was performed without major adverse events. Peri-procedural hyperthermia >37.5 °C occurred in 2 patients, hypothermia <35 °C in 8 cases. Interventional variables did not correlate significantly with pain scores, opioid dose, nor body temperature. 85.5% of patients experienced significant early pain relief within the first week after intervention. Post-interventional pain relief is associated with morphine equivalent opioid dose (p = 0.025) and treatment time (p = 0.040).Conclusion: While HIFU can be considered safe and effective treatment option, procedure-associated pain and temperature management represent challenges for the interdisciplinary HIFU intervention team. Especially short-term pain relief depends on the combined effort of the radiologist and anesthesiologist.

Diagnosis of peri-prosthetic loosening of total hip and knee arthroplasty using 18F-Fluoride PET/CT.

Periprosthetic loosening, either aseptic or induced by periprosthetic joint infection remains a major long term complication and challenge in orthopedics and trauma surgery. Sensitivity of potential loosening of the material and other causes of a painful prosthesis is essential for choosing the respective treatment option and providing the needed resources. 18F-Fluoride is a radiopharmaceutical which shows a high affinity to bone and a rapid blood clearance. The objective of this study was to assess 18F-Fluoride PET/CT´s sensitivity and specificity in diagnosing periprosthetic loosening in total hip and knee arthroplasty. We included 26 patients with 24 hip and 13 knee prostheses in our retrospective study with radiological or clinical suspicion of peri-prosthetic loosening at least one year after implantation. Results of 18F-Fluoride PET/CT imaging were compared with surgical results or clinical follow-up if surgery was not performed. On the basis of our data we found a sensitivity of 95.00 %, a specificity of 87.04 % and an accuracy of 89.19 % for 18F-Fluoride PET/CT. The results of our study show that 18F-Fluoride PET/CT is a useful and promising technique in diagnosing periprosthetic loosening of total hip and knee arthroplasties. Further investigation should focus on different uptake patterns of the isotope in periprosthetic joint infection and therefore distinguishing aseptic from septic loosening and enhancing the diagnostic value of this imaging method.

Advanced Pancreatic Cancer: High-Intensity Focused Ultrasound (HIFU) and Other Local Ablative Therapies. / Fortgeschrittenes Pankreaskarzinom: Hoch-intensiver fokussierter Ultraschall (HIFU) und andere lokal ablative Verfahren.

BACKGROUND: Locally advanced pancreatic cancer is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer-associated pain. Several local ablative therapies with both thermal and non-thermal sources have recently received significant attention as modern treatment options for local tumor control and symptomatic improvement. The following review article provides an overview of currently available techniques and their outcomes including our own experience with high-intensity focused ultrasound (HIFU) being one of the most exciting and innovative modalities. METHOD: Our experiences with HIFU treatment are based on 89 pancreatic cancer patients (UICC III-IV). Outcomes such as treatment-related changes in symptoms particularly in cancer pain and quality of life as well as local tumor response, safety and survival were compared to reported studies concerning HIFU, radiofrequency and microwave ablation, cryoablation, irreversible electroporation and stereotactic body radiation therapy. RESULTS: Even though all strategies appeared to be feasible, the unique feature of noninvasiveness represents a substantial advantage of the HIFU procedure. In 85 % of HIFU-treated patients, long-lasting pain relief was achieved. 50 % of patients did not require any analgesic treatment 6 weeks post-ablation. Unfortunately, pain palliation and quality-of-life outcomes are only rarely reported for other local treatment modalities. Tumor mass reduction could be achieved with all ablative therapies, with a mean tumor volume reduction of 60 % after 6 months in HIFU-treated pancreatic tumors. Differences in treatment-associated morbidity were reported. However, they are only partially comparable due to unbalanced study populations. CONCLUSION: Various local ablative treatment modalities are available and feasible for tumor mass reduction of advanced pancreatic cancer but with different symptomatic benefit for patients. An effective and long-lasting reduction of cancer-related pain was observed following HIFU without insertion of needles or electrodes. Randomized controlled studies for head-to-head comparison of these modalities are warranted in the near future. KEY POINTS: · Several ablative therapies are available for the local treatment of inoperable pancreatic cancer.. · Tumor mass and symptom reduction are main goals of local therapies.. · HIFU differs based on its noninvasive approach and low complication rate.. · HIFU enables effective long-lasting pain relief in > 80 % of patients.. · HIFU-associated pain relief is independent of tumor stage and metastatic status.. CITATION FORMAT: · Marinova M, Wilhelm-Buchstab T, Strunk H. Advanced Pancreatic Cancer: High-Intensity Focused Ultrasound (HIFU) and Other Local Ablative Therapies. Fortschr Röntgenstr 2019; 191: 216 - 227.

Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer.

PURPOSE: Pancreatic cancer (PaC) is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer pain in more than 80 % of patients. This prospective interventional study addresses the clinical effectiveness of ultrasound-guided high-intensity focused ultrasound (HIFU) treatment for patients with advanced-stage PaC, including pain perception, tumor size and survival benefit. MATERIALS AND METHODS: 50 patients with late-stage PaC underwent HIFU. Clinical assessment included evaluation of tumor volume by imaging and pain burden (pain severity, pain sensation, interference with daily activities) using the Brief Pain Inventory at baseline and follow-up. Median overall survival, progression-free survival and time to local progression were estimated using Kaplan-Meier analysis. RESULTS: In 84 % of patients, significant early relief of cancer-induced abdominal pain was achieved by HIFU independent of metastatic status; it persisted during follow-up. Tumor volume reduction was 37.8 ±â€Š18.1 % after 6 weeks and 57.9 ± 25.9 % after 6 months. 21 % of HIFU-treated patients had local tumor progression with a median time of 14.4 months from intervention. The median overall survival and progression-free survival were 16.2 and 16.9 months from diagnosis and 8.3 and 6.8 months from intervention. CONCLUSION: In patients with advanced pancreatic cancer and otherwise limited treatment options, HIFU resulted in significant early and long-lasting pain relief and tumor size reduction over time independent of metastatic status. Clinical data suggest an additional potential survival benefit.

Transjugular Intrahepatic Portosystemic Shunt (TIPS): Pathophysiologic Basics, Actual Indications and Results with Review of the Literature. / Transjugulärer intrahepatischer portosystemischer Stentshunt (TIPS): Pathophysiologische Grundlagen, gegenwärtige Indikationen und Ergebnisse mit Review der Literatur.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a non-selective portosystemic shunt created using endovascular techniques. During recent years technical improvements and new insights into pathophysiology have modified indications for TIPS placement. In this article we therefore want to discuss current knowledge. METHOD: A literature review was performed to review and discuss the pathophysiology, indications and results of the TIPS procedure. RESULTS: Established TIPS indications are persistent bleeding despite combined pharmacological and endoscopic therapy and rebleeding during the first five days. A new indication in the European recommendations is early TIPS placement within 72 hours, ideally within 24 hours, in patients bleeding from esophageal or gastroesophageal varices at high risk for treatment failure (e. g. Child-Pugh class C < 14 points or Child-Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy. For prevention of recurrent variceal hemorrhage in the recommendations, covered TIPS placement is the treatment of choice only after failed first-line therapy, although numerous TIPS studies show a prolonged time to rebleeding and a reduction of mortality. Similarly for secondary prophylaxis in patients with refractory ascites, covered TIPS placement may be considered only if the patient continues to be intolerant to NSBBs and is an appropriate TIPS candidate even though studies show that the TIPS procedure controls ascites, improves survival and renal function better than paracentesis. Potential indications for TIPS implantation are Budd-Chiari syndrome, acute portal vein thromboses, hydrothorax, hepatopulmonary and hepatorenal syndrome (Typ 2), portal hypertensive gastropathy (PHG) and prophylaxis of complications of abdominal surgery, very rarely bleeding in ectopic varices or in patients with chylothorax or chylous ascites. CONCLUSION: TIPS placement is an established procedure with a new indication as "early TIPS". In the European recommendations it is only the second-line therapy for prevention of recurrent variceal hemorrhage and for secondary prophylaxis in patients with refractory ascites although several studies showed a clear benefit of the TIPS procedure compared to ligation and NSBBs. KEY POINTS: · In addition to already established indications, new European recommendations suggest early TIPS placement in patients bleeding from esophageal or gastroesophageal varices at high risk for treatment failure.. CITATION FORMAT: · Strunk H, Marinova M, . Transjugular Intrahepatic Portosystemic Shunt (TIPS): Pathophysiologic Basics, Actual Indications and Results with Review of the Literature. Fortschr Röntgenstr 2018; 190: 701 - 711.

68Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost.

PURPOSE: The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model. METHODS: Twenty-one prostate cancer patients (70 years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations. RESULTS: Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p < 0.0001). For the integrated boost with 80 Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found. CONCLUSIONS: Our study demonstrates that the use of 68Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.

Mesenteric Vessel Patency Following HIFU Therapy in Patients with Locally Invasive Pancreatic Cancer.

PURPOSE: To evaluate the effects of HIFU therapy on visceral vessel patency in patients with inoperable locally invasive pancreatic cancer. MATERIALS AND METHODS: 50 pancreatic cancer patients (26 men, 24 women) aged 41 - 82 years (65.0 ±â€Š10.2) underwent ultrasonography (US) and computed tomography (CT) examinations before and within one day after HIFU treatment, as well as at follow-up at six weeks, three months and six months. Evaluation and grading were performed by two experienced independent radiologists according to a classification scheme based on vessel involvement, vessel diameter, patency, and defects in flow. RESULTS: Before HIFU treatment, arterial vessel involvement was noted in 42 patients, venous involvement in 47, and 47 patients presented with both. Superior mesenteric artery occlusion was found in three carcinomas while nearly half of the cases (n = 24) displayed signs of superior mesenteric vein, portal vein, or splenic vein occlusion. High-grade tumor-associated arterial narrowing was seen in ten patients. Despite vessel encasement and partially extensive propagation of collateral vessels, it was possible to safely perform HIFU treatment in all patients without complications. US and CT studies performed within one day after therapy did not show any change in vessel patency in 47 patients (94 %). Follow-up controls at the six-week mark revealed increased vessel narrowing and finally occlusion after six months in 11 patients due to tumor progression. CONCLUSION: This study demonstrates that HIFU treatment can be safely applied to pancreatic cancers enveloping large mesenteric vessels despite vessel narrowing or extensive collateral propagation. Most patients (94 %) did not experience adverse effects regarding vessel patency.

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer.

Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load. RESULTS: In patients with high tumor load, SUVmean was reduced to 61.5% in the lacrimal glands, to 56.6% in the parotid glands, to 63.7% in the submandibular glands, to 61.3% in the sublingual glands and to 55.4% in the kidneys (p < 0.001). Further significant differences were observed for brain, mediastinum, liver, spleen and muscle. Total tracer retention was higher in patients with high tumor load (p < 0.05). SUV in lacrimal, salivary glands and kidneys correlated negatively with PSA. MATERIALS AND METHODS: 135 patients were retrospectively evaluated. SUV was measured in the lacrimal and salivary glands, brain, heart, liver, spleen, kidneys, muscle and bone. SUV was correlated with visual tumor load, total tracer retention and PSA. CONCLUSIONS: Patients with high tumor load show a significant reduction of tracer uptake in dose-limiting organs. As similar effects might occur when performing RLT using Lu-177-labeled PSMA-ligands, individual adaptations of therapy protocols based on diagnostic PSMA PET imaging before therapy might help to further increase efficacy and safety of RLT.

Assessment of Bone Metastases in Patients with Prostate Cancer-A Comparison between 99mTc-Bone-Scintigraphy and [68Ga]Ga-PSMA PET/CT.

PURPOSE: Bone scintigraphy is the standard of reference in bone metastases in prostate cancer patients. However, new radiotracers employed in prostate-specific membrane antigen (PSMA)-ligands has led to the growing importance of PET/CT as diagnostic tool. The aim of our study was to investigate the difference between bone scan and PSMA-PET/CT for the detection of bone metastases in prostate cancer. METHODS: Thirty patients with bone metastases originating from prostate cancer were examined by 99mTc-MDP bone scan and 68Ga-PSMA-PET/CT within an average of 21 days. Bone scans were analyzed visually according to the number of lesions and using the software package ExiniBONE by Exini Diagnostics. PET/CT data was analyzed visually. Numbers of detected lesions were compared for the different methods for the whole patient and for different regions. In addition, results were compared to serum prostate-specific antigen (PSA), alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), pro gastrin releasing peptide (pGRP) and eastern cooperative oncology group (ECOG) performance status. RESULTS: In the bone scans, visual and semiautomatic lesion detection showed similar results with an average of 19.4 and 17.8 detected bone lesion per patient. However, in PSMA-PET/CT, on average double the numbers of lesions (40.0) were detected. The largest differences were found in the thorax and pelvis, which can be explained by the advantages of tomographic imaging. Bland-Altman analysis showed greater differences in patients with large numbers of bone metastases. CONCLUSION: No significant difference was found when using semiautomatic analysis compared to visual reading for bone scans. Fewer bone metastases were detected in bone scans than in PSMA-PET/CT. However, in none of our patients would the difference have led to clinical consequences. Therefore, it seems that for patients undergoing PSMA-PET/CT, there is no need to perform additional bone scans if the appropriate PET/CT protocols are applied.