Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

DEGRO practical guideline for partial-breast irradiation.

PURPOSE: This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI). METHODS: Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique. RESULTS: Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given. CONCLUSION: Guidelines are mandatory to assure optimal results of APBI using different techniques.

Mucinous versus medullary breast carcinoma: mammography, ultrasound, and MRI findings.

Mucinous and medullary breast cancers (BCs) have different histological substrates that manifest as different imaging features on mammography, ultrasound, and MRI. The aim of the present review is to demonstrate the differences between these two rare BC subtypes and to describe the microscopic features, review the imaging methods for detection of both cancer subtypes, illustrate the imaging findings and present useful pearls and pitfalls. Out of a total of 30 patients with mucinous BC and nine with medullary BC, we have selected typical and also unusual imaging features that best represent these cancers. The patients underwent a mammography and breast ultrasound followed by magnetic resonance imaging. We briefly exhibit histological characteristics for a better understanding of the imaging aspects.

Hypo- vs. normofractionated radiation therapy in breast cancer: A patterns of care analysis in German speaking countries.

AIM AND BACKGROUND: To assess the use of hypofractionated (HG-RT) versus normofractionated radiation therapy (NF-RT) in Breast Cancer in German speaking countries. MATERIALS AND METHODS: Between July 2017 and August 2017, an email-based survey was sent to all 1408 physicians that are members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 180 physicians including 10 private practice owners and 52 heads of departments. The majority (82.1%) of the participants had >15 years of experience in radiation therapy (RT). RESULTS: The majority (83.9%) of the heads of the departments agreed on using the normofractionated regimen of RT as standard treatment for breast cancer. Several physicians were skeptical about HF-RT with 6.5% of the heads refusing to use HF-RT. 40.3% of the departments had not seen the new German guidelines suggesting HF-RT as the standard treatment for all patients as positive or merely adopted a neutral position toward the guidelines (33.9%). The main points of criticism were increased side effects, an impaired toxicity profile and insufficient data. Most departments (46.8%) that perform HF-RT do so in an individual based manner. CONCLUSIONS: HF-RT remains controversial in German speaking countries. Our data shows that NF-RT remains the predominant method of treatment. HF-RT is only used in a defined group of patients as most German physicians agree that particular patients, especially those at higher risk of RT late effects, may benefit from a less intense, extended fractionation schedule.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Prognostic factors in stereotactic body radiotherapy of lung metastases.

PURPOSE: The aim of this study was to evaluate prognostic factors in patients with lung metastases who undergo lung stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: A total of 87 patients with 129 lung metastases who underwent SBRT between November 2004 and May 2012 were enrolled in this retrospective study. The patient collective consisted of 54 men (62.1%) and 33 women (37.9%); the median age was 65 years (range 36-88). The Karnofsky performance index was ≥70% (median 90%) for all cases, but one (60%). Adverse effects were categorized using the CTCAE 4.0 classification system. Retrospective analyses regarding patients' characteristics, progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and local tumor control rates (LTC) were performed. RESULTS: On univariate and multivariate analysis OS, DSS, and PFS were significantly (p < 0.05) better for patients with ≤3 lung metastases; no extrathoracic metastases at the time of the SBRT; a gross tumor volume (GTV) <7.7 cm3 and patients that received a staging that included positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) imaging. Furthermore, a longer OS was observed if newly diagnosed metastases during follow-up were limited to the lung (median survival: 43.7 months versus 21.7 months; p = 0.023). CONCLUSION: The number and pattern of metastases, and the size of the target volume are strong predictors for the outcome of patients receiving SBRT of lung tumors. FDG-PET/CT should be part of pretherapeutic staging before SBRT.

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model : A treatment planning study.

BACKGROUND AND PURPOSE: Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT). MATERIALS AND METHODS: In an orthotopic pancreatic cancer model, MRI/CT-based radiation treatment planning was established. Three irradiation techniques (rotational, 3D multifield, stereotactic) were performed with the SARRP system (Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed for each treatment setting. RESULTS: MRI with high soft tissue contrast improved imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise contouring of GTV and OARs, thus, providing a perfect basis for an improved dose distribution and coverage of the GTV for all advanced radiation techniques. CONCLUSION: An MRI/CT-based treatment planning for high-precision IGRT using different techniques was established in an orthotopic pancreatic tumor model. Advanced radiation techniques allow considering perfect coverage of GTV and sparing of OARs in the preclinical setting and reflect clinical treatment plans of pancreatic cancer patients.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Interobserver variability in target volume delineation of hepatocellular carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the German Society for Radiation Oncology (DEGRO).

BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. METHODS: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. RESULTS: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Protection of quality and innovation in radiation oncology: the prospective multicenter trial QUIRO of DEGRO: evaluation of time, attendance of medical staff, and resources during radiotherapy with tomotherapy.

PURPOSE: The technical progress in radiotherapy in recent years has been tremendous. This also implies a change of human and time resources. However, there is a lack of data on this topic. Therefore, the DEGRO initiated several studies in the QUIRO project on this subject. The present publication focuses on results for tomotherapy systems and compares them with other IMRT techniques. METHODS: Over a period of several months, time allocation was documented using a standard form at two university hospitals. The required time for individual steps in the treatment planning process was recorded for all involved professional groups (physicist, technician, and physician) by themselves. The time monitoring at the treatment machines was performed by auxiliary employees (student research assistants). Evaluation of the data was performed for all recorded data as well as by tumor site. A comparison was made between the two involved institutions. RESULTS: A total of 1,691 records were analyzed: 148 from head and neck (H&N) tumors, 460 from prostate cancer, 136 from breast cancer, and 947 from other tumor entities. The mean value of all data from both centers for the definition of the target volumes for H&N tumors took a radiation oncology specialist 75 min, while a physicist needed for the physical treatment planning 214 min. For prostate carcinomas, the times were 60 and 147 min, respectively, and for the group of other entities 63 and 192 min, respectively. For the first radiation treatment, the occupancy time of the linear accelerator room was 31, 26, and 30 min for each entity (H&N, prostate, other entities, respectively). For routine treatments 22, 18, and 21 min were needed for the particular entities. Major differences in the time required for the individual steps were observed between the two centers. CONCLUSION: This study gives an overview of the time and personnel requirements in radiation therapy using a tomotherapy system. The most representative analysis could be done for the room occupancy times during treatment in both centers. Due to the partly small amount of data and differing planning workflows between the two centers, it is problematic to draw a firm conclusion with regard to planning times. Overall, the time required for the tomotherapy treatment and planning is slightly higher compared to other IMRT techniques.

Localization and quantification of the delivered dose to the spinal cord. Predicting actual delivered dose during daily MVCT image-guided tomotherapy.

PURPOSE: The goal of the present work was to localize and quantify the actual delivered dose to the cervical spinal cord (SC) during head and neck cancer (H&N) treatment. MATERIALS AND METHODS: A total of 20 H&N patients treated with bilateral nodal irradiation with helical tomotherapy (HT) were analyzed. Daily MVCTs were performed for image guidance. On every second MVCT, the SC was recontoured and the delivered dose for the given treatment fraction (12 fractions per patient) was recalculated. The magnitude and localization (CT slice, spinal cord quadrant) of the Dmax to the SC on the planning CT (PLAN-Dmax) and of the actual delivered Dmax (a-Dmax) were analyzed. RESULTS: A systematic deviation from the PLAN-Dmax was observed in 15 out of 20 patients. Large interpatient variability of the a-Dmax in the spinal cord was noted (4.5±4%). Intrapatient variability in a-Dmax was, generally, minimal (1.8±2.7%). Throughout the treatment course, the higher dose was located in the same CT slices and in the same quadrants (anterior right and anterior left) for the same patient. CONCLUSION: Exact localization and quantification of the change of the a-Dmax can be made for most patients by recalculating the dose on the daily IGRT-MVCTs. This could be helpful in assessing whether replanning is necessary in patients with doses close to the known tolerance doses of the spinal cord.

Adaptive radiotherapy for soft tissue changes during helical tomotherapy for head and neck cancer.

PURPOSE: The goal of the present study was to assess the frequency and impact of replanning triggered solely by soft tissue changes observed on the daily setup mega-voltage CT (MVCT) in head and neck cancer (H&N) helical tomotherapy (HT). MATERIAL AND METHODS: A total of 11 patients underwent adaptive radiotherapy (ART) using MVCT. Preconditions were a soft tissue change > 0.5 cm and a tight mask. The dose­volume histograms (DVHs) derived from the initial planning kVCT (inPlan), the recalculated DVHs of the fraction (fx) when replanning was decided (actSit) and the DVHs of the new plan (adaptPlan) were compared. Assessed were the following: maximum dose (Dmax), minimum dose (Dmin), and mean dose (Dmean) to the planning target volume (PTV) normalized to the prescribed dose; the Dmean/fx to the parotid glands (PG), oral cavity (OC), and larynx (Lx); and the Dmax/fx to the spinal cord (SC) in Gy/fx. RESULTS: No patient had palpable soft tissue changes. The median weight loss at the moment of replanning was 2.3 kg. The median PTV Dmean was 100% for inPlan, 103% for actSit, and 100% for adaptPlan. The PTV was always covered by the prescribed dose. A statistically significant increase was noted for all organs at risk (OAR) in the actSit. The Dmean to the Lx, the Dmean to the OC and the Dmax to the SC were statistically better in the adaptPlan. No statistically significant improvement was achieved by ART for the PGs. No significant correlations between weight and volume loss or between the volume changes of the organs to each other were observed, except a strong positive correlation of the shrinkage of the PGs (ρ = + 0.77, p = 0.005). CONCLUSION: Soft tissue shrinkage without clinical palpable changes will not affect the coverage of the PTV, but translates into a higher delivered dose to the PTV itself and the normal tissue outside the PTV. The gain by ART in individual patients­especially in patients who receive doses close to the tolerance doses of the OAR­could be substantial.

Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy.

PURPOSE: The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). METHODS: Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. RESULTS: SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. CONCLUSION: This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity.

Respiratory gated [18F]FDG PET/CT for target volume delineation in stereotactic radiation treatment of liver metastases.

PURPOSE: The use of 4D-[(18)F]fluorodeoxyglucose (FDG) PET/CT in combination with respiratory gated magnet resonance imaging (MRI) in target volume definition for stereotactic radiation of liver metastases was investigated. METHODS AND MATERIALS: A total of 18 patients received respiration gated FDG-PET/CT and MRI. Data were fused using a rigid co-registration algorithm. The quality of the co-registration was rated on a scale from 1 (excellent) to 5 (poor) for co-registration of MRI with gated PET and ungated PET. Gross tumor volume (GTV) was delineated in CT (GTV (CT)), MRI (GTV(MRI)), and PET (GTV(PET)). MRI- and PET-based GTVs were defined by three observers each. Interobserver variability was calculated for all patients as well as for subgroups with and without previous treatment of liver metastases. All GTVs were compared for all patients and separately for patients with previous local therapy. In addition, a semiautomatic segmentation algorithm was applied on the PET images. RESULTS: Co-registration between MR and PET images was rated with 3.3 in average when non-gated PET was used and improved significantly (p < 0.01) to 2.1 using gated PET. The average GTV(CT) was 51.5 ml, GTV(MRI) 51.8 ml, and the average GTV(PET) 48.1 ml. Volumes delineated in MRI were 9.9% larger compared to those delineated in CT. Volumes delineated in PET were 13.8% larger than in MRI. The differences between the GTVs were more pronounced in patients with previous treatment. The GTVs defined in MRI showed an interobserver variability of 47.9% (84.1% with previous treatment and 26.2% without previous treatment). The PET-defined GTVs showed an interobserver variability of 21% regardless of previous treatment. Semiautomatic segmentation did not provide satisfying results. CONCLUSION: FDG-PET can distinguish vital tumor tissue and scar tissue, and therefore alters the GTV especially in patients with previous local treatment. In addition, it reduces the interobserver variability significantly compared to MRI. However, respiratory gated PET is necessary for good co-registration of PET and MRI.

Typical and unusual sonoelastographic patterns of breast cystic lesions: impact on BI-RADS classification.

PURPOSE: To describe the sonoelastographic appearance of breast cysts (simple, complicated-cysts with sedimentation and complex-cysts with internal solid parts). To assess the influence of sonoelastography on the BI-RADS classification of complicated cysts. MATERIALS AND METHODS: A prospective study was conducted and all cysts diagnosed by the same radiologist between May 2007 and July 2008 in our breast unit were included. Each lesion was assessed according to BI-RADS and the Tsukuba elasticity score using a Hitachi 8500 US device. Cytology or histopathology was obtained for complicated and complex cysts. RESULTS: 49 simple, 43 complicated and 14 complex cysts were detected. The elasticity patterns were divided into 4 categories: typical BGR (blue-green-red) pattern, appearance similar to that described for solid. lesions, variants of BGR, an inverse score of 3. The BGR pattern was predominant in breast cysts. Atypical elasticity patterns were mostly associated with complicated and complex cysts. BI-RADS classification of complicated cysts before and after elastography showed a statistically significant difference in terms of final category assessment (most of the complicated cysts were downgraded to BI-RADS 2 after elastography). CONCLUSION: Being aware of the wide spectrum of elastographic patterns of breast cysts and considering elastography when assessing the BI-RADS category of complicated cysts may lead radiologists to better patient management.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Helical TomoTherapy for locally advanced or recurrent breast cancer.

PURPOSE: We report our experience of using helical tomotherapy (HT) to treat large and irregular shaped loco-regional advanced breast cancer target volumes embracing various organs at risk. PATIENTS AND METHODS: We retrospectively analyzed 26 patients treated for very large, irregular shaped breast cancers. Patients were treated either with the intent to achieve local control in a primary setting (n = 14) or in a reirradiation setting (n = 12). The recurrence group was heavily pretreated with systemic therapy. Tumors were characterized by wide infiltration of the skin, encompassing mostly a complete hemithorax. The primary group underwent irradiation of supraclavicular, infraclavicular, axillary and parasternal lymphonodal region. Radiotherapy was combined with chemotherapy (n = 11). We assessed the PTV volume and its craniocaudal extension, the dose to the organs at risk, acute toxicity and survival. RESULTS: Median PTV was 2276 cm3 (1476-6837 cm3) with a median cranio-caudal extension of 28 cm (15-52 cm). The median dose to PTV was 40 Gy (32-60Gy). HT could be carried out in all patients without interruption. The acute toxicities were mild to moderate. The median LRFS and OS after radiotherapy was 21 and 57 months for the primary group versus 10 and 11 months for the recurrence group. Median PFS was 18 months (primary group) and 7 months (recurrence group). CONCLUSIONS: HT is feasible for advanced thorax embracing target volumes with acceptable acute toxicity. Both curative and palliative indications can be considered good indications based on treatment volume and anatomical constellation.

Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. METHODS: 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax). RESULTS: After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively. CONCLUSIONS: Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.