Extended therapy with [177Lu]Lu-PSMA-617 in responding patients with high-volume metastatic castration-resistant prostate cancer.

PURPOSE: The currently used scheme for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC) consists of 4-6 cycles of 6.0-7.4 GBq [177Lu]Lu-PSMA-617 each. This standard treatment scheme has proved safe and effective resulting in objective response in most patients with no significant toxicity. Many patients, however, show high-volume residual tumor burden after the sixth cycle and may benefit from treatment continuation. Extended treatment with additional cycles has been withheld due to concerns on potential increased toxicity. METHODS: Twenty-six patients with high-volume residual tumor burden (according to CHAARTED) after standard RLT with [177Lu]Lu-PSMA-617 and no alternative treatment option received additional RLT cycles reaching a median of 10 (range 7-16) cycles with a mean activity of 7.4 ± 0.9 GBq per cycle. Response assessment with [68Ga]Ga-PSMA-11 PET/CT was done every 2-3 cycles or if disease progression was clinically suspected or based on change in PSA value (according to the PCWG3 criteria). Toxicity was measured using routine blood work up including blood counts, liver and renal function, and was graded according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan-Meier method. RESULTS: Further PSA decline of 33 ± 28% during the extended treatment was observed in 21/26 (81%) patients, whereas 5/26 (19%) patients showed a PSA increase; correspondingly in 11/21 patients with an initial response (PR or SD) to extended cycles, treatment was discontinued due to progressive disease, whereas six (23%) patients achieved low-volume residual disease. Two (8%) patients died without showing progression, and two (8%) patients are still under therapy. The median progression-free survival was 19 (95% CI: 15-23) months, and the overall survival was 29 (95% CI: 18-40) months. Grade ≥ 3 hematological toxicities occurred in 4/26 (15%) patients during treatment extension, and nephrotoxicity (grade ≥ 3) was observed in 1/26 (4%) patient during the follow-up. CONCLUSION: Extended radioligand therapy is a feasible treatment option in patients with high-volume residual tumor after the completion of standard treatment with six cycles of [177Lu]Lu-PSMA-617. Improved survival and the acceptable safety profile warrant further investigation of the concept of additional cycles in selected patients.

177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study).

PURPOSE: Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice. METHODS: We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late-end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan-Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum-maximum) values are given. RESULTS: Patients received 3 (1-13) 177Lu-PSMA-617 activities (6.5 [2.5-11.6] GBq/cycle) every 5.7 (3.0-11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4-6.6) months and OS, 14.5 (95%CI 11.5-17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5-5.5], p < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%). CONCLUSIONS: In a large, prospectively observed "real-world" cohort with late-stage/end-stage mCRPC and conventional treatment failure, 177Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.

[Radiofrequency ablation of benign thyroid nodules]. / Radiofrequenzablation benigner Schilddrüsenknoten.

Radiofrequency ablation is an effective tool to treat benign thyroid nodules up to about 100 ml. It is well tolerated and is - together with echopulse therapy - currently the most frequently used technique in Germany for the local therapy of benign thyroid nodules. Overall, a volume reduction of about 50 % to 70 % can be expected. Cystic nodules and mixed-pattern lesions respond slightly better than solid nodules. Initial volume, structure and echogenicity are important parameters influencing the therapeutic efficacy. Bipolar as well as monopolar methods are used - the choice of the method depends mainly on the personal experience. For bigger nodules, the bipolar technique is preferred. Cooled systems should be favored, especially when using larger probes. Serious side effects are rare (< 1 %) and transient in most cases.

Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing 177Lu-PSMA-617 radioligand therapy.

PURPOSE: Little is known about the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) against liver metastases of metastatic castration-resistant prostate cancer (mCRPC). We retrospectively analyzed efficacy-related outcomes of 177Lu-PSMA-617 RLT in this setting and potential predictors of those outcomes. METHODS: Twenty-eight consecutive mCRPC patients with liver metastases given 177Lu-PSMA-617 RLT were analyzed retrospectively. Their planned regimen was 4-6 cycles at 6 ± 2-week intervals; the mean activity/cycle was 6.5 ± 0.5 GBq. Hepatic response was determined by modified positron emission tomography response criteria in solid tumors; association of such response with overall survival (OS) was tested, as were relationships of the selected patient, disease, and treatment characteristics with hepatic progression-free survival (PFShep) and OS. Survival analyses used Kaplan-Meier curves, log-rank test at p < 0.05 significance, and Cox proportional-hazards modeling. RESULTS: Median (minimum-maximum) follow-up was 37.5 (2.3-50.6) months. In liver metastases, complete or partial response was observed in 6 patients (21%) each, and stable disease in 1 (4%), for hepatic disease control in 46%. Overall, median (95% confidence interval) PFShep was 5.7 (2.2-9.2) months, and OS, 11.7 (3.0-20.4) months. Patients with hepatic disease control did not reach the median OS, while those with hepatic progressive disease had median OS (95% confidence interval) of 6.4 (1.6-11.1) months. In multivariate analysis, hepatic disease control by 177Lu-PSMA-617 RLT was significantly independently associated with OS, as was a prostate-specific antigen decline of ≥ 50% after 2 RLT cycles, and good baseline performance status (Eastern Cooperative Oncology Group 0-1). Hepatic tumor burden (≤ 25% vs. > 25% of liver volume) had no apparent relationship with hepatic tumor response, PFShep, or OS. CONCLUSION: 177Lu-PSMA-617 RLT frequently controlled liver metastases, resulting in long PFShep and significantly improved OS. Hepatic tumor burden appeared to lack any relationship with treatment efficacy, supporting 177Lu-PSMA-617 RLT of late-stage/end-stage mCRPC with liver metastases.

Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma.

AIM: Distant metastasis has a negative impact on survival in differentiated thyroid carcinoma (DTC). The timing of this manifestation, however, is of unknown prognostic relevance. The aim of this retrospective study was to investigate the potential significance of discriminating synchronous versus metachronous distant metastases (SDM vs. MDM) for the outcome of patients with DTC. METHODS: We retrospectively analyzed a consecutive cohort of n = 89 patients with distant metastases of DTC (43 with follicular, 46 with papillary DTC histology; mean age 52.6 ± 17.7 years) undergoing radioiodine treatment at our institution. All patients were treated with the same protocol consisting of ablative radioiodine therapy (RIT, 3.7 GBq) and one post-ablation treatment after 3 months (3.7-11.1 GBq). Further cycles of RIT were administered for recurrent, progressive or newly developed metastatic disease. We distinguished 2 types of distant metastases according to the time of manifestation: SDM (within ≤12 months after DTC diagnosis) and MDM (occurring >12 months after diagnosis). Tumor-related survival was analyzed using the Kaplan-Meier method. Uni- and multivariate analyses including the Cox proportional hazards model were performed with a significance level of p < 0.05. RESULTS: The mean follow-up period was 13.8 ± 1.2 years. SDM were present in 49 (55.1 %), MDM in 40 (44.9 %) patients. MDM were associated with shorter tumor-related survival (p = 0.002). 5-year and 10-year survival rates were 68.5 % and 34.8 % for MDM, and 84.3 % and 66.9 % for SDM, respectively. Within both age subgroups of <45 and ≥45 years, SDM were also linked with longer survival. No effect on tumor-related survival was found for the co-variables sex, lymph node metastases and histologic type. CONCLUSION: Distinguishing synchronous from metachronous manifestation of distant metastases may add an important prognostic feature to risk stratification in DTC, as proven metachronous appearance is associated with impaired survival.

Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success.

PURPOSE: Increased articular 99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy. METHODS: Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples. RESULTS: Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022). CONCLUSIONS: Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.

Diffusion-weighted magnetic resonance imaging predicts survival in patients with liver-predominant metastatic colorectal cancer shortly after selective internal radiation therapy.

OBJECTIVES: To investigate whether quantifications of apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) can predict overall survival (OS) in patients with liver-predominant metastatic colorectal cancer (CRC) following selective internal radiation therapy with 90Yttrium-microspheres (SIRT). METHODS: Forty-four patients underwent DWI 19 ± 16 days before and 36 ± 10 days after SIRT. Tumour-size and intratumoral minimal ADC (minADC) values were measured for 132 liver metastases on baseline and follow-up DWI. Optimal functional imaging response to treatment was determined by receiver operating characteristics and defined as ≥22 % increase in post-therapeutic minADC. Survival analysis was performed with the Kaplan-Meier method and Cox-regression comparing various variables with potential impact on OS. RESULTS: Median OS was 8 months. The following parameters were significantly associated with median OS: optimal functional imaging response (18 vs. 5 months; p < 0.001), hepatic tumour burden <50 % (8 vs. 5 months; p = 0.018), Eastern Cooperative Oncology Group performance scale <1 (10 vs. 4 months; p = 0.012) and progressive disease according to Response and Evaluation Criteria in Solid Tumours (8 vs. 3 months; p = 0.001). On multivariate analysis, optimal functional imaging response and hepatic tumour burden remained independent predictors of OS. CONCLUSION: Functional imaging response assessment using minADC changes on DWI may predict survival in CRC shortly after SIRT. KEY POINTS: • Relative minADC changes may predict survival in liver-predominant metastatic colorectal cancer following SIRT • Intratumoral minADC changes by ≥22 % were best to predict an improved overall survival • Functional imaging response assessment is feasible before anatomic tumour-size changes occur • minADC changes might guide future therapy management in sequential lobar radioembolization approaches.

Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative (124)I-NaI-PET/CT in patients with papillary thyroid cancer.

PURPOSE: Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both (124)I-NaI and (18)F-FDG along with high-resolution cervical ultrasound. METHODS: Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by (18)F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in (124)I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in (18)F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS). RESULTS: Incomplete metastatic lymph node resection captured by (124)I-NaI PET/CT (n = 33) was an independent risk factor for recurrence (61 % vs 25 %, p = 0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7-9.2], p = 0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p = 0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3-6.4], p = 0.007). CONCLUSIONS: Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with (124)I-Na and (18)F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.

Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer.

PURPOSE: The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with (90)Y-labelled microspheres. METHODS: A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent (18)F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUVmax) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. RESULTS: The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. CONCLUSION: These are the first findings to show that molecular response assessment in CRC using (18)F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies.

Specific efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in advanced neuroendocrine tumours of the small intestine.

PURPOSE: Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with (177)Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. METHODS: A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with (177)Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. RESULTS: The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2%). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1%), minor response in 19 (31.1%), stable disease in 29 (47.5%) and progressive disease in 5 (8.2%) patients. The disease control rate was 91.8%. Median progression-free survival (PFS) and overall survival (OS) was 33 [95% confidence interval (CI) 25-41] and 61 months (95% CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95% CI 1.0-4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95% CI 1.5-5.5, p < 0.001) at baseline. CONCLUSION: PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.

Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with (177)Lu-octreotate.

PURPOSE: Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine-allowing only approximate estimates of GFR-the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. METHODS: Nephrotoxicity was analysed using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with (177)Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by (99m)Tc-DTPA clearance versus serum creatinine. RESULTS: The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m(2) per year, relative yearly reduction -1.8 ± 18.9%). Fifteen patients (21%) experienced a mild (2-10 ml/min/m(2) per year) and 16 patients (22%) a significant (>10 ml/min/m(2) per year) decline of GFR following PRRT. However, 11 patients (15%) showed an increase of >10 ml/min/m(2) per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3%) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15% of the assessments and led to underestimation in 12% of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function. CONCLUSION: Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss >2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.

Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours.

PURPOSE: We assessed the outcome and toxicity of salvage therapy (repeat treatment) with (177)Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). METHODS: We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. RESULTS: Radiographic responses consisted of complete response in 1 patient (3.0%), partial response in 6 patients (18.2%), minor response in 1 patient (3.0%), stable disease in 14 patients (42.4%), and progressive disease in 11 patients (33.3%). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95% CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2%). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. CONCLUSION: PRRT with (177)Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.

Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours.

PURPOSE: The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with (177)Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). METHODS: We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with (177)Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial (99m)Tc-DTPA clearance measurements. RESULTS: The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked to impaired OS, on the other hand, were a reduced performance status (Karnofsky score ≤ 70 %, p = 0.007), a high hepatic tumour burden (≥ 25 % liver volume, p = 0.017), and an elevated plasma level of neuron-specific enolase (NSE >15 ng/ml, p = 0.035). CONCLUSION: The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient's performance status, tumour burden and baseline plasma NSE level.

Impact of Sleeve Gastrectomy on Uric Acid Levels in Patients with Obesity: A Comparative Study.

PURPOSE: This study aimed to investigate the incidence of hyperuricemia in obese individuals with or without metabolic syndrome and assess the impact of sleeve gastrectomy surgery on the amelioration of hyperuricemia and metabolic syndrome. MATERIALS AND METHODS: A prospective study was conducted on patients with obesity who were candidates for laparoscopic sleeve gastrectomy. These patients were diligently followed for 1 year after the surgical procedure. The assessment of hyperuricemia and metabolic syndrome was carried out both before and one year after the surgery. RESULTS: A total of 198 patients (30 males and 168 females) underwent sleeve gastrectomy. After 1 year, there was a notable decline in the prevalence of hyperuricemia, decreasing from 77 to 36 cases (a reduction of 46.75%) among females and from 18 to 8 cases (a reduction of 44.44%) among males. Prior to the surgery, 60.6% of patients (120 out of 198) were diagnosed with metabolic syndrome, and 36.7% of these patients exhibited improvements in their metabolic syndrome status. Among individuals with metabolic syndrome, significant enhancements were observed in various anthropometric and laboratory measurements, including reductions in hypertriglyceridemia, hyperuricemia, and hypercholesteremia. A logistic regression analysis revealed that in females, changes in creatinine, glomerular filtration rate (GFR), weight loss, body mass index (BMI), and triglyceride reduction all had a notable impact on the likelihood of recovering from hyperuricemia. CONCLUSION: These findings underscore the clinical relevance of this surgical intervention in managing obesity-related conditions.

Safety and Efficacy of Selective Internal Radionuclide Therapy with 90Y Glass Microspheres in Patients with Progressive Hepatocellular Carcinoma after the Failure of Repeated Transarterial Chemoembolization.

Transarterial chemoembolization (TACE) is currently the standard of care in patients with unresectable hepatocellular carcinoma (HCC), and selective internal radionuclide therapy (SIRT) with 90Y microspheres is mainly used as an alternative modality in patients considered poor candidates for TACE. Treatment with sorafenib is the recommended option for patients with progressive disease after TACE. This study aims to evaluate the safety and efficacy of SIRT with glass microspheres in patients with progressive HCC after repeated TACE who are not eligible for treatment with sorafenib. Forty-seven patients with progressive HCC after a median of three TACE sessions (range 2-14) underwent SIRT (3.5 ± 1.5 GBq; liver target dose 110-120 Gy). Toxicity was recorded 4 and 12 weeks after treatment and reported according to the Common Terminology Criteria for Adverse Events Version 5.0. Treatment response was assessed three months after SIRT using multiphase computed tomography and modified criteria in solid tumors (mRECIST). Survival analyses were performed using Kaplan-Meier curves and a Cox proportional hazards model for uni- and multivariate analyses. Significant but reversible hepatotoxicity (≥grade 3) occurred in five patients (11%). No radioembolization-induced liver disease (REILD) was observed. The number of previous TACE sessions and cumulative administered activity did not predict the incidence of post-SIRT significant hepatotoxicity. Treatment responses consisted of partial responses in 26 (55%), stable disease in 12 (26%), and progressive disease in 9 (19%) patients. The median overall survival (OS) was 11 months (95% confidence interval (CI), 9-13), and objective responses to SIRT were associated with a longer OS (p = 0.008). Significant hepatotoxicity (≥grade 3) after SIRT was a contributor to impaired survival (median OS 6 months (95% CI, 4-8) vs. 12 months (95% CI, 10-14), p < 0.001). SIRT with glass microspheres is a safe and effective salvage treatment for patients with progressive HCC refractory to TACE who are considered poor candidates for sorafenib treatment.

Miniaturized electromagnetic tracking enables efficient ultrasound-navigated needle insertions.

Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe. This results in specialized devices or introduces additional hardware, limiting the ergonomics of both the scanning and insertion process. We developed the first ultrasound (US) navigation solution designed to be used as a non-permanent accessory for existing US devices while maintaining the ergonomics during the scanning process. A miniaturized EMT source is reversibly attached to the US probe, temporarily creating a combined modality that provides real-time anatomical imaging and instrument tracking at the same time. Studies performed with 11 clinical operators show that the proposed navigation solution can guide needle insertions with a targeting accuracy of about 5 mm, which is comparable to existing approaches and unaffected by repeated attachment and detachment of the miniaturized tracking solution. The assistance proved particularly helpful for non-expert users and needle insertions performed outside of the US plane. The small size and reversible attachability of the proposed navigation solution promises streamlined integration into the clinical workflow and widespread access to US navigated punctures.

Hepatic volume changes induced by radioembolization with 90Y resin microspheres. A single-centre study.

PURPOSE: Lobar radioembolization (RE) of the liver can result in reduction in volume of the ipsilateral lobe as well as hypertrophy of the contralateral lobe. Theoretically, hypertrophy of the contralateral liver lobe after RE could increase the chance of a successful liver resection, especially in patients with limited liver function reserve. The aim of this preliminary study was to evaluate the early effects of RE with resin microspheres on the volumes of the liver lobes and spleen. METHODS: We retrospectively investigated 24 patients (12 women, 44-78 years old) with different types of cancer and liver-dominant metastatic disease who had undergone RE of the liver with resin microspheres. Changes in the volumes of the liver lobes and spleen were quantified by CT before and about 4 to 8 weeks after treatment. RESULTS: Of the 24 patients, 17 suffered from metastases in both liver lobes (group A) and 7 had metastases only in the right liver lobe (group B). The patients in the group A underwent sequential treatment starting with the right liver lobe. The median administered dose was 1.75 GBq. RE was associated with a median increase in volume of the left liver lobe of 34 % (P < 0.001) and a median decrease in volume of the right liver lobe of 11 % (P = 0.03). The volume of the spleen showed a median increase of 17 % (P = 0.01). Separate analysis of the two groups showed a median increases in volume of the left liver lobe of 30 % (P = 0.001) in group A and 70 % (P = 0.01) in group B. There was no correlation between the injected dose and the volume alteration (r = 0.1-0.3). CONCLUSION: RE of the right liver lobe with resin microspheres caused a significant increase in the volume of the left liver lobe. This may allow liver resection in patients with metastases in the right liver lobe and a small left liver lobe.

Heat sink effects in thyroid bipolar radiofrequency ablation: an ex vivo study.

The study aimed to investigate heat sink effects in radiofrequency ablation (RFA) under thyroid-specific conditions. In an ex vivo model, bovine thyroid lobes were ablated using bipolar RFA with 2.0 kJ energy input at a power level set to 10 W (n = 35) and 25 W (n = 35). Glass vessels (3.0 mm outer diameter) placed within the ablation zone were used to deliver tissue perfusion at various flow rates (0, 0.25, 0.5, 1, 5, 10, 20 ml/min). Temperature was measured in the proximity of the vessel (Tv) and in the non-perfused contralateral region of the ablation zone (Tc), at equal distances to the ablation electrode (d = 8 mm). Maximum temperature within the perfused zone was significantly lowered with Tv ranging from 54.1 ± 1.5 °C (20 ml/min) to 56.9 ± 1.5 °C (0.25 ml/min), compared to Tc from 63.2 ± 3.5 °C (20 ml/min) to 63.2 ± 2.6 °C (0.25 ml/min) (10 W group). The cross-sectional ablation zone area decreased with increasing flow rates from 184 ± 12 mm2 (0 ml/min) to 141 ± 20 mm2 (20 ml/min) at 10 W, and from 207 ± 22 mm2 (0 ml/min) to 158 ± 31 mm2 (20 ml/min) in the 25 W group. Significant heat sink effects were observed under thyroid-specific conditions even at flow rates ≤ 1 ml/min. In thyroid nodules with prominent vasculature, heat dissipation through perfusion may therefore result in clinically relevant limitations to ablation efficacy.

The influence of thionamides on intra-thyroidal uptake of 131I during radioiodine-131 treatment of Graves' disease.

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

Thyroid papillary cancer elements arising from struma ovarii with benign peritoneal strumosis: Utility of iodine-123 imaging in diagnostics and treatment planning.

Key Clinical Message: In this case of struma ovarii a right-sided ovarian mass contained features of papillary thyroid cancer. Diagnostic iodine-123 revealed multiple foci of extraovarian spread, likely as a manifestation of concomitant peritoneal strumosis. Unilateral oophorectomy, partial peritonectomy, and adjuvant iodine-131 treatment were performed for successful curative treatment. Abstract: Struma ovarii is a rare form of mature teratoma defined by a predominance of thyroid tissue. Approximately 5% of all ovarian strumae exhibit malignant transformation. Due to their extreme rarity, there has been a lack of consensus concerning uniform diagnostic criteria. Appropriate, risk-stratified treatment strategies also remain widely unelaborated, based only on a small number of cases reported in the literature. We describe the case of a 35-year-old female, who presented after undergoing unilateral oophorectomy for a right-sided ovarian mass. Histological workup revealed a struma ovarii containing papillary thyroid cancer (PTC). Postoperative I-123 scintigraphy with single photon emission computed tomography (SPECT) detected multifocal extra-ovarian spread to the peritoneum, containing likely benign strumosis upon pathological examination. The subsequent treatment strategy involved an ablative concept including total thyroidectomy and subsequent I-131 radioiodine therapy. Throughout a 3-year follow-up, the patient has remained without recurrence with thyroglobulin levels ranging below detection limits. Surgical resection with adjuvant radioiodine therapy is a curative therapeutic strategy in cases of struma ovarii with thyroid-type carcinoma and peritoneal strumosis. Its benefits lay in avoiding more extensive surgery, potentially maintaining fertility, facilitating follow-up, and minimizing the risk of recurrence. Reliable criteria for risk stratification are needed to identify patients who are most likely to benefit from this treatment approach.