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Background In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification. Methods In 16 patients, weekly blood samples ( n  = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters. Results Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5. Conclusions Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Radiofrequency ablation (RFA) is an established treatment option for malignancies located in the liver. RFA-induced irreversible coagulation necrosis leads to the release of danger signals and cellular content. Hence, RFA may constitute an endogenous tumor vaccination, stimulating innate and adaptive immune responses, including tumor-antigen specific T cells. This may explain a phenomenon termed abscopal effect, namely tumor regression in untreated lesions evidenced after distant thermal ablation or irradiation. In this study, we therefore assessed systemic and local immune responses in individual patients treated with RFA. For this prospective clinical trial, patients with liver metastasis from colorectal carcinoma (mCRC) receiving RFA and undergoing metachronous liver surgery for another lesion were recruited ( = 9) during a 5-year period. Tumor and non-malignant liver tissue samples from six patients were investigated by whole transcriptome sequencing and tandem-mass spectrometry, characterizing naturally presented HLA ligands. Tumor antigen-derived HLA-restricted peptides were selected by different predefined approaches. Further, candidate HLA ligands were manually curated. Peripheral blood mononuclear cells were stimulated with epitope candidate peptides, and functional T cell responses were assessed by intracellular cytokine staining. Immunohistochemical markers were additionally investigated in surgically resected mCRC from patients treated with ( = 9) or without RFA ( = 7). In all six investigated patients, either induced immune responses and/or pre-existing T cell immunity against the selected targets were observed. Multi-cytokine responses were directed against known tumor antigens such as cyclin D1 but also against a (predicted) mutation contained in ERBB3. Immunohistochemistry did not show a relevant influx of immune cells into distant malignant lesions after RFA treatment ( = 9) as compared to the surgery only mCRC group ( = 7). Using an individualized approach for target selection, RFA induced and/or boosted T cell responses specific for individual tumor antigens were more frequently detectable as compared to previously published observations with well-characterized tumor antigens. However, the witnessed modest RFA-induced immunological effects alone may not be sufficient for the rejection of established tumors. Therefore, these findings warrant further clinical investigation including the assessment of RFA combination therapies e.g., with immune stimulatory agents, cancer vaccination, and/or immune checkpoint inhibitors.

Objectives Melanomas arising from mucosa are rare and associated with a poor prognosis. This study aims to provide an analysis of metastatic pathways, time intervals, factors influencing metastatic spread and organs for distant metastases. Methods A total of 116 patients with mucosal melanomas of different sites were included. The mean follow-up interval was 47 ± 52 months. Patients were assigned to two different metastatic pathways, either presenting loco-regional lymph node metastases as first spread or direct distant metastases. The distribution of distant metastases was assessed. Results Twenty-six patients presented with a pre-existing metastatic spread and were not assigned to pathways. Of the included patients, 44 developed metastases after treatment of the primary tumour; 25 patients directly developed distant metastases; 16 patients developed regional lymph node metastases prior to distant metastases. Location of the primary tumour in the upper airway or GI tract and advanced T stage were significant risk factors of direct distant metastases. Distant metastases are mainly located in the lung, the liver and non-regional lymph nodes. Conclusions Mucosal melanomas show a high rate of direct distant metastases rather than regional lymph node metastases. Thus the follow-up should always include a whole-body cross-sectional imaging in high-risk tumours. Key points • Mucosal melanomas show a high rate of direct distant metastases. • T stage and primary location are predictors for direct distant metastases. • Distant metastases were mainly found in lung, liver and lymph nodes. • Follow-up of a high-risk mucosal melanoma should include whole-body imaging.

BackgroundRadiofrequency ablation (RFA) is a minimal-invasive, local therapy in patients with circumscribed metastatic disease. Although widely used, long time survival analysis of treated liver metastases is still pending while also analysing the patients’ experience of MR-based radiofrequency.MethodsMonocentric, retrospective analysis of long-time overall and progression free survival (OS; PFS) of 109 patients, treated with MRI-guided hepatic RFA between 1997 and 2010, focusing on colorectal cancer patients (CRC). Complimentary therapies were evaluated and Kaplan Meier-curves were calculated. Patients’ experience of RFA was retrospectively assessed in 28 patients.Results1-, 3-, 5-, 10-year OS rates of 109 patients with different tumour entities were 83.4%, 53.4%, 31.0% and 22.9%, median 39.2 months, with decreasing survival rates for larger metastases size. For 72 CRC patients 1-, 3-, 5-, 10-year OS rates of 90.2%, 57.1%, 36.1% and 26.5% were documented (median 39.5 months). Thereof, beneficial outcome was detected for patients with prior surgery of the CRC including chemotherapy (median 53.0 months), and for liver metastases up to 19 mm (28.5% after 145 months). Hepatic PFS was significantly higher in patients with liver lesions up to 29 mm compared to larger ones (p = 0.035). 15/28 patients remembered RFA less incriminatory than other applied therapies.ConclusionsThis is the first single-centre, long-time OS and PFS analysis of MRI-guided hepatic RFA of liver metastases from different tumour entities, serving as basis for further comparison studies. Patients’ experience of MR based RFA should be analysed simultaneously to the performed RFA in the future.

Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations. 116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages. We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas. Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p < 0.0001).

Background Combination therapy using hepatic resection (HR) and intra-operative thermal ablation is a treatment approach for patients with technically unresectable liver malignancies. The aim of this study was to investigate safety, survival and local recurrence rates for patients with technically unresectable liver tumors undergoing HR and separate percutaneous MR-guided thermoablation procedure as an alternative approach. Methods Data from all patients with primary or secondary hepatic malignancies treated at a single institution between 2004 and 2018 with combined HR and MR-guided percutaneous thermoablation was collected and retrospectively analyzed. Complications, procedure related information and patient characteristics were collected from institutional records. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. Results A total of 31 patients (age: 62.8 ± 9.1 years; 10 female) with hepatocellular carcinoma (HCC; n  = 7) or hepatic metastases ( n  = 24) were treated for 98 hepatic tumors. Fifty-six tumors (mean diameter 28.7 ± 23.0 mm) were resected. Forty-two tumors (15.1 ± 7.6 mm) were treated with MR-guided percutaneous ablation with a technical success rate of 100%. Local recurrence at the ablation site occurred in 7 cases (22.6%); none of these was an isolated local recurrence. Six of 17 patients (35.3%) treated for colorectal liver metastases developed local recurrence. Five patients developed recurrence at the resection site (16.1%). Non-local hepatic recurrence was observed in 18 cases (58.1%) and extrahepatic recurrence in 11 cases (35.5%) during follow-up (43.1 ± 26.4 months). Ten patients (32.3%) developed complications after HR requiring pharmacological or interventional treatment. No complication requiring therapy was observed after ablation. Median survival time was 44.0 ± 7.5 months with 1-,3-, 5-year overall survival rates of 93.5, 68.7 and 31.9%, respectively. The 1-, 3- and 5-year disease-free survival rates were 38.7, 19.4 and 9.7%, respectively. Conclusion The combination of HR and MR-guided thermoablation is a safe and effective approach in the treatment of technically unresectable hepatic tumors and can achieve long-term survival.

We evaluated a magnetic resonance (MR)-conditional high-power microwave ablation system. An ex vivo 1.5-T evaluation was conducted by varying the sequence (T1-weighted volume interpolated breath-hold examination, T1w-VIBE; T1-weighted fast low-angle shot, T1w-FLASH; T2-weighted turbo spin-echo, T2w-TSE), applicator angulation to B (A-to-B ), slice orientation, and encoding direction. Tip location error (TLE) and artefact diameters were measured, and influence of imaging parameters was assessed with analysis of variance and post hoc testing. Twenty-four ex vivo ablations were conducted in three bovine livers at 80 W and 120 W. Ablation durations were 5, 10, and 15 min. Ablation zones were compared for short-axis diameter (SAD), volume, and sphericity index (SI) with unpaired t test. The artefact pattern was similar for all sequences. The shaft artefact (4.4 ± 2.9 mm, mean ± standard deviation) was dependent on the sequence (p = 0.012) and the A-to-B (p < 0.001); the largest shaft diameter was measured with T1w-FLASH (6.3 ± 3.4 mm) and with perpendicular A-to-B (6.7 ± 2.4 mm). The tip artefact (1.6 ± 0.7 mm) was dependent on A-to-B (p = 0.001); TLE was -2.6 ± 1.0 mm. Ablation results at the maximum setting (15 min, 120 W) were SAD = 42.0 ± 1.41 mm; volume = 56.78 ± 3.08 cm , SI = 0.68 ± 0.05. In all ablations, SI ranged 0.68-0.75 with the smallest SI at 15 min and 120 W (p = 0.048). The system produced sufficiently large ablation zones and the artefact was appropriate for MR-guided interventions.

Objectives To compare the results of CT- vs MR-guided radiofrequency ablation (RFA) of liver metastases (LM) from colorectal cancer after 10 years of follow-up in an observational, retrospective, and multicentric study. Methods A total of 238 patients with 496 LM were treated with RFA either with CT (CT group) or magnetic resonance (MR group) guidance. Every ablated LM was assessed and followed up with diagnostic MRI. Technical success, technique efficacy, predictive factors, recurrence rates, and overall survival were assessed. Results The CT group comprised 143 patients and the MR group 77 patients. Eighteen patients underwent ablation with both modalities. Technical success per patient and per lesion was 88% and 93% for CT and 87% and 89.6% for MR, and technique efficacy was 97.1% and 98.6% for CT and 98.7% and 99.3% for MR respectively. Local recurrence following the first ablation (primary patency) occurred in 20.1% (CT) vs 4.6% (MR) ( p  < 0.001). Residual liver tumor, size of LM, and advanced N and M stage at initial diagnosis were independent predictors for overall survival in both groups. The median overall survival measured from first RFA treatment was 2.6 years. The 1-year, 5-year, and 10-year survival were 85.9%, 25.5%, and 19.1% respectively. Conclusions The MR group had significantly better local control compared to the CT group. There was no significant difference in patient survival between the two groups. Clinical relevance statement MR-guided radiofrequency ablation of colorectal liver metastases is safe and effective, and offers better local control than CT-guided ablation. Key Points • Imaging modality for radiofrequency ablation guidance is an independent predictor of local recurrence in colorectal liver metastases. • MR-guided radiofrequency ablation achieved better local control of liver metastases from colorectal cancer than CT-guided. • The number and size of liver metastases are, among others, independent predictors of survival. Radiofrequency ablation with MR guidance improved clinical outcome but does not affect survival.

Objectives Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. Methods Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years ± 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm ± 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post-ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months ± 2.6 (1-10 months). Results Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 ± 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ ± 21.7 (9-87 kJ) and 24.7 min ± 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm ± 10.5 (16-65 mm) and 52.7 mm ± 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. Conclusions Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. Key Points • Planning, applicator placement and therapy monitoring are possible without using contrast enhancement • Energy transmission from the generator to the scanner room is safely possible • MR-guided microwave ablation provides effective treatment of hepatic malignancies in one session • Therapy monitoring is possible without applicator retraction from the ablation site

PurposeEvaluation of technique effectiveness, patient safety and ablation parameters of MR-guided microwave ablation in hepatic malignancies using an MR-conditional high-power microwave ablation system.Materials and MethodsInstitutional review board approval and informed patient consent were obtained. Patients who underwent MR-guided microwave ablation of hepatic malignancies in a 1.5T wide-bore scanner using a perfusion-cooled high-power microwave ablation system with a maximum generator power of 150 W were included. Ablation parameters comprising procedure durations, net ablation duration, applicator positions and ablation zone dimensions were recorded. Adverse events were classified according to the CIRSE classification system. Technique effectiveness was assessed after 1 month. Follow-up was conducted with contrast-enhanced MRI and ranged from 1 to 20 months (mean: 6.1 ± 5.4 months).ResultsTwenty-one consecutive patients (age: 63.4 ± 10.5 years; 5 female) underwent 22 procedures for 28 tumours (9 hepatocellular carcinomas, 19 metastases) with a mean tumour diameter of 14.6 ± 5.4 mm (range: 6–24 mm). Technique effectiveness was achieved in all lesions. Tumours were treated using 1.7 ± 0.7 applicator positions (range: 1–3). Mean energy and ablation duration per tumour were 75.3 ± 35.4 kJ and 13.3 ± 6.2 min, respectively. Coagulation zone short- and long-axis diameters were 29.1 ± 6.4 mm and 39.9 ± 7.4 mm, respectively. Average procedure duration was 146.4 ± 26.2 min (range: 98–187 min). One minor complication was reported. Five patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed during initial follow-up.ConclusionMR-guided high-power microwave ablation provides safe and effective treatment of hepatic malignancies with short ablation times and within acceptable procedure durations.