BackgroundAfter focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-18F-Fluoroethyl)-L-Tyrosine positron emission tomography (18F-FET PET) in patients with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy of brain metastases.MethodsTwenty-two patients with 34 brain metastases (median age 61.9 years) were included. Due to follow-up scan evaluations after repeated treatment in a subset of patients, a total of 50 lesions with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy could be evaluated. 18F-FET PET analysis included the assessment of maximum and mean tumor-to-background ratio (TBRmax and TBRmean) and analysis of time-activity-curves (TAC; increasing vs. decreasing) including minimal time-to-peak (TTPmin). PET parameters were correlated with histological findings and radiological-clinical follow-up evaluation.ResultsTumor recurrence was found in 21/50 cases (15/21 verified by histology, 6/21 by radiological-clinical follow-up) and radiation-induced changes in 29/50 cases (5/29 verified by histology, 24/29 by radiological-clinical follow-up). Median clinical-radiological follow-up was 28.3 months (range 4.2–99.1 months). 18F-FET uptake was higher in tumor recurrence compared to radiation-induced changes (TBRmax 2.9 vs. 2.0, p < 0.001; TBRmean 2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBRmax and 1.95 for TBRmean (sensitivity 86 %, specificity 79 %). Increasing TACs and long TTPmin were associated with radiation-induced changes, decreasing TACs with tumor recurrence (p = 0.01). By combination of TBR and TACs, sensitivity and specificity could be increased to 93 and 84 %.ConclusionsIn patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, 18F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions.

BackgroundIn the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis.Patients and methods340 patients with 1–3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications.ResultsMedian overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS ≤ 70: 122 days; KPS > 70: 342 days), for RPA (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II: 281 days; RPA class III: 130 days), irradiated volume (≤2.5 ml: 354 days; > 2.5 ml: 234 days), prescribed dose (≤18 Gy: 235 days; > 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/− whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging.ConclusionsSRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients.

Background: The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. Methods: A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1–5 mm, >5 mm, or >10 mm. Results: Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1–5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. Conclusions: A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.

Background: There is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT. Methods: Patients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses. Results: Twenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14-24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/ IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004). Conclusion: SRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing. Trial registration: The institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128-14).

BackgroundTo report our results with postoperative or definitive radiation therapy in head and neck sarcomas.MethodsWe performed a retrospective analysis of 26 patients suffering from head and neck sarcomas, who received postoperative or definitive radiation therapy between 2003 and 2012. Median age was 64 years (19–88) and 69 % were male. Tumor locations were skull (including skin) in 31 %, paranasal sinus/orbita in 27 % and neck (including pharynx/larynx) in 42 %. Median tumor size was 4.6 cm (1-12 cm). 22 patients (85 %) presented in primary situation. Stage at presentation (UICC 7th for soft tissue sarcomas) was as follows: Ia:4 %, IIa:50 %, IIb:15 %, III:31 %. All except one patient suffered from high grade lesions (G2/3 FNCLCC), predominantly angiosarcoma (35 %), MFH (19 %) and synovial sarcoma (15 %). Surgery was performed in 21 pts (81 %), resulting in free margins in 10 (38 %), microscopically positive margins in 6 (23 %) and gross residual disease in 5 (19 %). Median dose to the primary tumor region was 66Gy (45-72Gy) in conventional fractionation, using 3D-CRT in 65 %, IMRT in 27 % and electrons in 8 %. 50 % of the patients also received sequential chemotherapy.ResultsMedian follow up was 39 months (8–136). We observed three local recurrences, transferring into estimated 3- and 5-year local control rates of 86 %. One additional patient failed distantly, resulting in 3- and 5-year freedom from treatment failure rates of 82 %. Four patients have deceased, transferring into 3- and 5-year overall survival rates of 88 % and 82 %, respectively. Only two of the four deaths were sarcoma related. Maximum acute toxicity (CTCAE 3.0) was grade 1 in 27 % of the patients, grade 2 in 50 % and grade 3 in 23 %. Severe acute toxicity was mainly represented by mucositis and dysphagia. Maximum late toxicity was grade 1 in 31 %, grade 2 in 15 % and grade 3 in 19 % of the patients. Severe late toxicity included skin ulceration (n = 1), dysphagia with persistent tube dependency (n = 1), persistent sinusitis (n = 1) and hearing loss (n = 2).ConclusionExcellent local control and overall survival rates can be achieved with postoperative or definitive radiation therapy with acceptable acute and late toxicities in patients suffering from sarcomas of the head and neck region.