[Monocentric experiences of stereotactic body radiation therapy (SBRT) for advanced hepatocellular carcinomas (BCLC-C)]. / Monozentrische Erfahrungen mit stereotaktischer Bestrahlung (SBRT) beim fortgeschrittenen hepatozellulären Karzinom im Stadium BCLC-C.

Hepatocellular carcinomas (HCCs) are highly malignant primary liver cancers with poor prognosis and limited treatment options in advanced stages of disease. Treatment of HCC requires interdisciplinary discussion and multimodal therapy approaches. Beside established loco-regional and systemic therapies, stereotactic body radiation therapy (SBRT) gained increasing importance over recent years. First results of early clinical studies indicate high rates of local control with a good safety profile. In the present work, we evaluated our single center experiences with SBRT in patients with advanced HCCs.Ten patients with 16 SBRTs were included and retrospectively analyzed in this case collection. All patients presented in advanced tumor stages with vascular invasion and/or metastases, but preserved liver function. Two patients were treated only with SBRT, two after TACE and six patients received SBRT in addition to systemic therapy. In most of the cases SBRT were applied to intrahepatic lesions. Large tumor thromboses, lymph nodes as well as bone metastases were irradiated in one, three and five fractions with a median overall dose of 38 Gy. We observed a good local tumor control with a good safety profile in all cases. No severe complications occurred in combination to sequential as well as additive approach to loco-regional or systemic treatments.In conclusion, our experiences confirm results of early clinical studies indicating safe use and good local control rates also in advanced stages of HCC with preserved liver function.

Long-term survival of patients after ipilimumab and hypofractionated brain radiotherapy for brain metastases of malignant melanoma: sequence matters.

PURPOSE: Since the introduction of ipilimumab (IPI) for the treatment of patients with metastatic malignant melanoma, we have observed remarkable responses after hypofractionated whole brain irradiation (WBRT) or stereotactic radiotherapy (STX) for brain metastases of malignant melanoma. We sought to investigate the impact of the sequence of these treatment modalities. METHODS: We retrospectively evaluated the survival of melanoma patients with brain metastases who were treated with WBRT or STX and received IPI in close temporal relation between October 2010 and March 2015. Follow-up was obtained until November 2016. A total of 27 patients with advanced melanoma and brain metastases who were treated with WBRT before 2010, and who had not received IPI, served as historical controls. RESULTS: We identified a total of 41 patients of whom 15 were treated with STX, 7 with a combination of STX and WBRT and 19 with WBRT alone. All patients received at least 2 doses of IPI. The median time interval between radiotherapy and IPI was 2 months. Patients treated with IPI after radiotherapy had a censored median survival of 11 months, compared with 3 months for the patients who received IPI prior to radiotherapy. Patients who received IPI before radiotherapy showed a similar survival as historical controls, who had not received IPI. We observed long-term survivors after radiotherapy of brain metastases followed by IPI. CONCLUSIONS: These data suggest that the sequence of RT and immune checkpoint inhibition with IPI may be crucial for the success of combined modality treatment of melanoma brain metastases.

NHL-ChirEx: An interprofessional cross-border education initiative in the Greater Region with a focus on radiation morbidity and patient safety.

NHL-ChirEx is an interprofessional cross-border education project that addresses the potential excess of radiation induced morbidity throughout the radiation planning and treatment process. NHL-ChirEx is supported by ESTRO and the University of the Greater Region and has been recently approved and funded under INTERREG VA Programme.

Quantification of Radiation Biomarkers in Leukocytes of Breast Cancer Patients Treated with Different Modalities of 3D-CRT or IMRT.

The goal of this study was to determine whether the quantification of radiation biomarkers in peripheral leukocytes of 111 breast cancer patients after adjuvant treatment with different modalities of three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) revealed any difference in the patients' radiation burden by out-of-field doses and an associated risk of second malignancies. Whole-breast radiation therapy was performed by 3D-CRT using either a hard wedge (n = 32) or a virtual wedge (n = 49) at dose rates of 3 and 6 Gy per min each. Patients receiving additional radiotherapy to lymph nodes were treated by 3D-CRT (n = 21) or IMRT (n = 9). DNA damage was measured as γ-H2AX foci (n = 111) and as unstable chromosomal aberrations (n = 15) in leukocytes drawn 30 min and 24 h after the first radiation fraction, respectively. The individual basal yield and radiation sensitivity ex vivo were assessed in leukocytes obtained before the first treatment. After radiation therapy, the average rate of γ-H2AX foci and chromosomal aberrations per leukocyte were dependent on multiple parameters of irradiation: the treatment volume, the administered equivalent whole-body dose, the number of monitor units and the beam-on time. Different modalities of radiation therapy caused significant variations in the levels of both radiation biomarkers irrespective of the treatment volume and administered dose, and in particular, a twofold higher rate after IMRT compared to 3D-CRT. Any deviation in biomarker response between radiation therapy techniques was directed by a linear dependence on the absolute beam-on time. However, the dispersion of γ-H2AX foci in peripheral leukocytes after radiation therapy correlated very well with the relative distribution of dose in the whole-body volume for each radiation therapy technique. In conclusion, the induction of radiation biomarkers in leukocytes of breast cancer patients by different radiotherapy modalities is dominated by general variables of irradiation. There was no significant difference in peripheral dose exposure observed in the investigated radiation therapy techniques. Radiotherapy techniques with prolonged absolute beam-on time increase the fraction of exposed leukocytes with pronounced risks for hematologic toxicities or immunosuppressive side effects.

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.