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Purpose: The aim of this study was to evaluate the role of preoperative and postoperative external beam radiation therapy (EBRT) in the treatment of resectable soft tissue sarcomas (STSs) of different tumor locations., Methods: A systematic literature search was performed to identify studies investigating the effects of EBRT (versus no EBRT) on local recurrence (LR) and overall survival (OS) or comparing different EBRT sequences. Random effects meta-analyses were calculated and presented as cumulative odds ratios (ORs)., Results: Sixteen studies (n = 3958 patients) comparing EBRT versus no EBRT, including one randomized controlled trial (RCT) in extremity sarcoma, were analyzed. EBRT appeared to reduce LR in both retroperitoneal tumors (OR 0.47, p < 0.0001) and other locations (OR 0.49, p = 0.001). OS was improved by EBRT in retroperitoneal STSs (OR 0.37, p < 0.0001) but not in other tumor locations. Eleven studies (n = 2140), including one RCT, compared preoperative and postoperative radiotherapy. LR was less frequent following preoperative EBRT in retroperitoneal STSs (OR 0.03, p = 0.02), as well as in other tumor locations (OR 0.67, p = 0.01), while wound complications in extremity sarcoma were more frequent following preoperative EBRT (OR 2.92, p < 0.0001). Several studies included in this meta-analysis bear a high risk of bias and no RCT has been published for retroperitoneal STS., Conclusions: This meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

Background: Treatment of recurrent gynecologic cancer is a challenging issue. Aim of the study was to investigate clinical features and outcomes of patients with recurrent gynecologic malignancies who underwent resection including IOERT (intraoperative electron radiation therapy) with regard to clinical outcome and potential predictive factors or subgroups that benefit most from this radical treatment regime., Methods: A total of 36 patients with recurrent gynecologic malignancies (cervical (n = 18), endometrial (n = 12) or vulvar cancer (n = 6)) were retrospectively identified through hospital databases in accordance with institutional ethical policies. Patient characteristics and outcomes were assessed. Survival data was analyzed using the Kaplan-Meier-method and log-rank-test, categorical variables were analyzed with chi-square-method., Results: For the entire cohort 1-/2-/5-year Overall Survival (OS) was 65.3 %/36.2 %/21.7 %. Patients with endometrial, cervical, and vulvar carcinoma had a 1-/2-/5-year OS of 83.3 %/62.5 %/50 %, 44.5 %/25.4 %/6.4 %, and 83.3 %/16.7 %/16.7 %, respectively. Patients with endometrial carcinoma showed a significantly better OS (p = 0.038). 1-/2-/5-year Local Progression-free Survival (LPFS) for the entire cohort was 44.1 %/28 %/21 % with 76.2 %/61 %/40.6 % for endometrial, 17.2 %/0 %/0 % for cervical, and 40 %/20 %/20 % for vulvar cancer, respectively. Patients with endometrial cancer showed a significantly (p = 0.017) and older patients a trend (p = 0.059) for a better LPFS. 1-/2-/5-year Distant Progression-free Survival (DPFS) for the entire cohort was 53.1 %/46.5 %/38.7 % with 74.1 %/74.1 %/74.1 % for endometrial, 36.7 %/36.7 %/0 % for cervical, and 60 %/30 %/30 % for vulvar cancer, respectively. There was a significantly better DPFS for older patients (p = 0.015) and a trend for a better DPFS for patients with endometrial carcinoma (p = 0.075)., Conclusion: The radical procedure of resection combined with IOERT seems to be a valid curative treatment option for patients with recurrent endometrial carcinoma with 5-year survival rates of 50 %. For patients with cervical or vulvar cancer this treatment should be considered a rather palliative one and must be weighted carefully against other treatment options like chemotherapy, targeted therapies or new highly conformal radiotherapy techniques.

Simple Summary: Around 30% of the patients receiving intracranial particle therapy develop radiogenic reactions of the brain. There are a wide range of symptoms, ranging from asymptomatic blood–brain barrier disorders to life-threatening brain necrosis. The aim of our retrospective study is to assess the patterns of occurrence in patients treated for skull base chordoma and chondrosarcoma with protons or carbon ions. Furthermore, we aimed to develop a prognostic model for the prediction of radiation reactions. Background: The current study aims to evaluate the occurrence of temporal lobe reactions and identify possible risk factors for patients who underwent particle therapy of the skull base. Methods: 244 patients treated for skull base chordoma (n = 144) or chondrosarcoma (n = 100) at the Heidelberg Ion Beam Therapy Center (HIT) using a raster scan technique, were analyzed. Follow-up MRI-scans were matched with the initial planning images. Radiogenic reactions were contoured and analyzed based on volume and dose of treatment. Results: 51 patients with chordoma (35.4%) and 30 patients (30%) with chondrosarcoma experienced at least one temporal lobe reaction within the follow-up period (median 49 months for chondrosarcoma, 62 months for chordoma). Age, irradiated volume, and dose values were significant risk factors for the development of temporal lobe reactions with the highest significance for the value of DMax-7 being defined as the dose maximum in the temporal lobe minus the 7cc with the highest dose (p = 0.000000000019; OR 1.087). Conclusion: Temporal lobe reactions are a common side effect after particle therapy of the skull base. We were able to develop a multivariate model, which predicted radiation reactions with a specificity of 99% and a sensitivity of 52.2%. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of locally advanced rectal cancer has been subject to pronounced changes based on the results of recent prospective trials. New paradigms have been introduced, including the shift of systemic treatment components from adjuvant to neoadjuvant setting (total neoadjuvant therapy), the omission of surgery in patients with clinical complete responses after neoadjuvant treatment (non-operative management) and the introduction of upfront immunotherapy in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. We developed an institutional treatment algorithm which may serve as a practical tool for treating physicians without any claim to general validity. Total neoadjuvant therapy (TNT)—the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery—may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians—without any claim to general validity. [ABSTRACT FROM AUTHOR]

• IORT + EBRT results in excellent LC in extremity STS even with unfavourable factors. • IORT + preoperative EBRT results in excellent LC in retroperitoneal STS. • Dose escalation via IORT is feasible with limited rates of acute and late toxicities. To describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). A panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. Based on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS. In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity. In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. IORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials. [ABSTRACT FROM AUTHOR]

Purpose: The need for four‐dimensional (4D) treatment planning becomes indispensable when it comes to radiation therapy for moving tumors in the thoracic and abdominal regions. The primary purpose of this study is to combine the actual breathing trace during each individual treatment fraction with the Linac's log file information and Monte Carlo 4D dose calculations. We investigated this workflow on multiple computed tomography (CT) datasets in a clinical environment for stereotactic body radiation therapy (SBRT) treatment planning. Methods : We have developed a workflow, which allows us to recalculate absorbed dose to a 4DCT dataset using Monte Carlo calculation methods and accumulate all 4D doses in order to compare them to the planned dose using the Linac's log file, a 4DCT dataset, and the patient's actual breathing curve for each individual fraction. For five lung patients, three‐dimensional‐conformal radiation therapy (3D‐CRT) and volumetric modulated arc treatment (VMAT) treatment plans were generated on four different CT image datasets: a native free‐breathing 3DCT, an average intensity projection (AIP) and a maximum intensity projection (MIP) CT both obtained from a 4DCT, and a 3DCT with density overrides based on the 3DCT (DO). The Monte Carlo 4D dose has been calculated on each 4DCT phase using the Linac's log file and the patient's breathing trace as a surrogate for tumor motion and dose was accumulated to the gross tumor volume (GTV) at the 50% breathing phase (end of exhale) using deformable image registration. Results: ΔD98% and ΔD2% between 4D dose and planned dose differed largely for 3DCT‐based planning and also for DO in three patients. Least dose differences between planned and recalculated dose have been found for AIP and MIP treatment planning which both tend to be superior to DO, but the results indicate a dependency on the breathing variability, tumor motion, and size. An interplay effect has not been observed in the small patient cohort. Conclusions: We have developed a workflow which, to our best knowledge, is the first incorporation of the patient breathing trace over the course of all individual treatment fractions with the Linac's log file information and 4D Monte Carlo recalculations of the actual treated dose. Due to the small patient cohort, no clear recommendation on which CT can be used for SBRT treatment planning can be given, but the developed workflow, after adaption for clinical use, could be used to enhance a priori 4D Monte Carlo treatment planning in the future and help with the decision on which CT dataset treatment planning should be carried out. [ABSTRACT FROM AUTHOR]

Respiratory motion remains a source of major uncertainties in radiotherapy. Respiratory correlated computed tomography (referred to as 4DCT) serves as one way of reducing breathing artifacts in 3D-CTs and allows the investigation of tumor motion over time. The quality of the 4DCT images depends on the data acquisition scheme, which in turn is dependent on the vendor. Specifically, the only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based reconstruction using triggers provided by an external surrogate signal. The accuracy is strongly dependent on the method of trigger generation. Two consecutive triggers are used to define a breathing cycle which is divided into respiratory phases of equal duration. The goal of this study is to identify if there are advantages in the usage of local-amplitude based sorting (LAS) of the respiration motion states, in order to reduce image artifacts and improve 4DCT quality. Furthermore, this study addresses the generation and optimization of a clinical workflow using as surrogate motion monitoring system the Sentinel™ (C-RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB CT scanner. For that purpose, a phantom study using 10 different breathing waveforms and a retrospective patient study using the 4DCT reconstructions of 10 different patients has been conducted. The error in tumor volume has been reduced from 2.9 ± 3.7% to 2.7 ± 2.6% using optimal cycle-based triggers ( manipulated CBS ) and to 2.7 ± 2.2% using LAS in the phantom study. Moreover, it was possible to decrease the tumor volume variability from 5.0 ± 3.6% using the original cycle-based triggers ( original CBS ) to 3.5 ± 2.5% using the optimal triggers and to 3.7 ± 2.7% using LAS in the patient data analysis. We therefore propose the usage of the manipulated CBS, also with regard to an accurate and safe clinical workflow. [ABSTRACT FROM AUTHOR]

Purpose: Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution.Methods: Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated.Results: In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5‑ and 10-year OS was 89 and 80%, respectively. Estimated 5‑ and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS.Conclusions: The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible. [ABSTRACT FROM AUTHOR]

Purpose: To report our experience with surgery, intraoperative radiation therapy (IORT), and external beam radiation therapy (EBRT) in retroperitoneal soft-tissue sarcoma.Methods and Materials: We conducted a retrospective evaluation of 156 patients (69 primary, 87 recurrent) treated with IORT since 1991. The dominant histology was dedifferentiated liposarcoma (49%); 89% of lesions were high grade. Median tumor size was 11 cm. Surgery resulted in gross complete resection in 92%, and 65% had microscopically positive margins. Median IORT dose was 15 Gy. A total of 114 patients (73%) received additional EBRT (preoperatively n=38, postoperatively n=76, median dose 45 Gy).Results: Median follow-up was 38 months (49 months in survivors). The 3- and 5-year local control (LC) rates were 57% and 50%, respectively. On univariate analysis, LC was significantly associated with primary versus recurrent status, histology, grade, Union for International Cancer Control (UICC) stage, resection margin, and addition of EBRT. The 5-year LC was 71% in the primary situation and 79% after R0 resection. On multivariate analysis only disease status, grade, resection margin, and addition of EBRT remained statistically significant. The 3- and 5-year overall survival (OS) rates were 66% and 56%. On univariate analysis, OS was significantly associated with primary versus recurrent status, histology, grade, UICC stage, resection margin, and timing of EBRT. The 5-year OS was 63% in the primary situation and 68% after R0 resection. On multivariate analysis only disease status, grade, and resection margin remained independent prognostic factors. Perioperative mortality was 1%, and major complications occurred in 34% (mainly wound complications).Conclusions: Treatment with surgery, IORT, and EBRT is feasible and resulted in good LC and OS, with acceptable morbidity in this unfavorable patient cohort. Incomplete resection and recurrent status resulted in clearly inferior outcomes. Reasonable efforts should be made during primary treatment to prevent the onset of a local recurrence. [ABSTRACT FROM AUTHOR]

Background: Desmoid-type fibromatosis (DF) is a aggressive (myo)fibroblastic neoplasm with an infiltrative growth and a tendency to local recurrence. Resection of the tumour and/or radiation were proposed as principal treatment. The aim of this retrospective study was to analyze the local control rates focusing on the effect of surgical margins and radiotherapy.Methods: From 1981 to 2014, 44 patients had been treated. Fifty four therapies had been applied, in 50 cases surgery +/- radiation therapy, NSAIDs or chemotherapy. In 4 cases a conservative approach was chosen. Thirty seven patients had primary, 17 recurrent disease. Endpoint was either local recurrence (LR), progression of residual disease or rare non-metastatic secondary lesions at the same extremity.Results: The mean age was 39,4 years. In 17 cases a R0, in 27 a R1 and in 6 cases a R2 resection was achieved. Four patients were treated conservatively. All together in 21 cases radiotherapy, in 5 NSAIDs, in 3 imatinib and in 2 cases each tamoxifen or chemotherapy had been applied. The median follow-up was 119 months. 5-year recurrence free survival after resection was 78%. 10 (20.4%) patients developed LR between 5 and 42 months after therapy. Recurrent disease was a negative factor on LR. Margins, radiotherapy, sex, or size of the tumour had no significant impact on LR. Patients younger than 40 years had a significant higher risk of LR.Conclusions: Surgical margins are less important than keeping function. Radiotherapy might be an option in unresectable lesions, the role of adjuvant radiotherapy is controversially discussed. [ABSTRACT FROM AUTHOR]

Despite the important improvements made in the fields of surgery, chemotherapy and radiation therapy, pancreatic cancer remains one of the most lethal malignancies. Improved outcomes with novel chemotherapy regimes led again to increased attention on the role of localized radiotherapy, since local tumor progression causes significant morbidity and mortality in patients. Even after resection local failure rates are as high as 50-80%. The immediate proximity to critical structures (bone marrow, spinal cord, kidneys, liver, and intestine) limits the dose of radiation that can be administered to the tumor bed with conventional external beam radiation therapy (EBRT). The intraoperative radiotherapy (IORT) appears to be an ideal therapeutic strategy for this disease, having the advantage of enabling the delivery of high doses of radiation to areas that are at risk for microscopic disease, saving critical organs and reducing the possibility of inducing radiotoxicity. This technique allows a theoretical increase in the radiation therapeutic index to tumor compared to the adjacent organs at risk (OAR). The aim of this review is to update and comment on IORT in the multidisciplinary management of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials. [ABSTRACT FROM AUTHOR]

Background: Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume.Methods: We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (t x , t y , t z ) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed.Results: The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach.Conclusions: Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used.Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.Methods/design: This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome.Discussion: This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment.Trial Registration: NCT02319408;Registration: December 29, 2014. [ABSTRACT FROM AUTHOR]

Background: To report our results with postoperative or definitive radiation therapy in head and neck sarcomas. Methods: We 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. Results: Median 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). Conclusion: Excellent 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. [ABSTRACT FROM AUTHOR]

Background: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). Methods: We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Results: Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Conclusion: Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study was conducted to evaluate the long-term results of irradiation with carbon ions in a raster scanning technique in patients with skull base chordomas. METHODS Between 1998 and 2008, a total of 155 patients (76 men and 79 women) with a median age of 48 years (range, 15 years-85 years) were irradiated with carbon ions using a raster scan technique. The irradiation was performed at the Society for Heavy Ion Research in Darmstadt, Germany. The median total dose was 60 gray (relative biological effectiveness) at 3 gray (relative biological effectiveness) per fraction. The median boost planning target volume was 70 mL (range, 2 mL-294 mL). Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method, whereas long-term toxicity was evaluated via questionnaires. RESULTS The median follow-up was 72 months (range, 12 months-165 months). All patients had residual macroscopic tumors at the initiation of radiotherapy. The authors observed 55 local recurrences during follow-up, as well as systemic disease progression in 4 patients. The resulting 3-year, 5-year, and 10-year LC rates were 82%, 72%, and 54%, respectively, whereas the 3-year, 5-year, and 10-year OS rates were 95%, 85%, and 75%, respectively. Age <48 years and a boost volume >75 mL were associated with a significantly improved LC and OS. Primary treatment resulted in a significantly better OS probability. No higher late toxicity could be detected after carbon ion treatment. CONCLUSIONS Carbon ion therapy appears to be a safe and effective treatment for patients with skull base chordoma, resulting in high LC and OS rates. Cancer 2014;120:3410-3417. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: To evaluate disease control, overall survival and prognostic factors in patients with locally recurrent rectal cancer after IOERT-containing multimodal therapy. Methods: Between 1991 and 2006, 97 patients with locally recurrent rectal cancer have been treated with surgery and IOERT. IOERT was preceded or followed by external beam radiation therapy (EBRT) in 54 previously untreated patients (median dose 41.4 Gy) usually combined with 5-Fluouracil-based chemotherapy (89%). IOERT was delivered via cylindric cones with doses of 10–20 Gy. Adjuvant CHT was given only in a minority of patients (34%). Median follow-up was 51 months.Results: Margin status was R0 in 37%, R1 in 33% and R2 in 30% of the patients. Neoadjuvant EBRT resulted insignificantly increased rates of free margins (52% vs. 24%). Median overall survival was 39 months. Estimated 5-year rates for central control (inside the IOERT area), local control (inside the pelvis), distant control and overall survival were 54%, 41%, 40% and 30%. Resection margin was the strongest prognostic factor for overall survival (3-year OS of 80% (R0), 37% (R1), 35% (R2)) and LC (3-year LC 82% (R0), 41% (R1), 18% (R2)) in the multivariate model. OS was further significantly affected by clinical stage at first diagnosis and achievement of local control after treatment in the univariate model. Distant failures were found in 46 patients, predominantly in the lung. 90-day postoperative mortality was 3.1%. Conclusion: Long term OS and LC can be achieved in a substantial proportion of patients with recurrent rectal cancer using a multimodality IOERT-containing approach, especially in case of clear margins. LC and OS remain limited in patients with incomplete resection. Preoperative re-irradiation and adjuvant chemotherapy may be considered to improve outcome. [ABSTRACT FROM AUTHOR]

Background In this retrospective investigation we analyzed outcome and toxicity after intensity-modulated reirradiation of recurrent head and neck cancer. Methods Thirty-eight patients with local recurrent head and neck cancer were evaluated. The median dose of initial radiotherapy was 61 Gy. Reirradiation was carried out with step-and-shoot intensity-modulated radiotherapy (median dose: 49 Gy). Results Median overall survival was 17 months, and the 1- and 2-year overall survival rates were 63% and 34%. The 1- and 2-year local control rates were 57% and 53%. Distant spread occurred in 34%, and reirradiation induced considerable late toxicity in 21% of the patients. Thirty-two percent showed increased xerostomia after reirradiation. The risk for xerostomia was significantly higher for cumulative mean doses of ≥45 Gy to parotid glands. Considering median cumulative maximum doses of 53 Gy to the spinal cord and 63 Gy to the brainstem, no late toxicities were observed. Conclusions Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer is feasible with acceptable toxicity and yields encouraging rates of local control and overall survival. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Background: The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. Methods/Design: This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrolment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrolment. Discussion: This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome. Trial registration: ClinicalTrials.gov - NCT01027221. [ABSTRACT FROM AUTHOR]

Background: Giant cell tumors are rare neoplasms, representing less than 5% of all bone tumors. The vast majority of giant cell tumors occurs in extremity sites and is treated by surgery alone. However, a small percentage occurs in pelvis, spine or skull bones, where complete resection is challenging. Radiation therapy seems to be an option in these patients, despite the lack of a generally accepted dose or fractionation concept. Here we present a series of five cases treated with high dose IMRT. Patients and Methods: From 2000 and 2006 a total of five patients with histologically proven benign giant cell tumors have been treated with IMRT in our institution. Two patients were male, three female, and median age was 30 years (range 20 - 60). The tumor was located in the sacral region in four and in the sphenoid sinus in one patient. All patients had measurable gross disease prior to radiotherapy with a median size of 9 cm. All patients were treated with IMRT to a median total dose of 64 Gy (range 57.6 Gy to 66 Gy) in conventional fractionation. Results: Median follow up was 46 months ranging from 30 to 107 months. Overall survival was 100%. One patient developed local disease progression three months after radiotherapy and needed extensive surgical salvage. The remaining four patients have been locally controlled, resulting in a local control rate of 80%. We found no substantial tumor shrinkage after radiotherapy but in two patients morphological signs of extensive tumor necrosis were present on MRI scans. Decline of pain and/or neurological symptoms were seen in all four locally controlled patients. The patient who needed surgical salvage showed markedly reduced pain but developed functional deficits of bladder, rectum and lower extremity due to surgery. No severe acute or late toxicities attributable to radiation therapy were observed so far. Conclusion: IMRT is a feasible option in giant cells tumors not amendable to complete surgical removal. In our case series local control was achieved in four out of five patients with marked symptom relief in the majority of cases. No severe toxicity was observed. [ABSTRACT FROM AUTHOR]

Background: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Patients and Methods: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Results: Median age was 61 years (range, 26–81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications ≥Grade 3 were seen in 17% and 13% of patients, respectively. Conclusion: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer. [Copyright &y& Elsevier]

Purpose: This study assesses the long-term outcome of patients with retroperitoneal soft-tissue sarcomas treated by maximal resection in combination with intraoperative electron-beam therapy (IOERT) and postoperative external-beam radiotherapy. Methods and Materials: From 1991 to 2004, 67 patients were treated with curative intent for primary (n = 26) or recurrent (n = 41) retroperitoneal soft-tissue sarcoma. All patients underwent maximal resection in combination with IOERT (mean dose, 15 Gy), 45 patients underwent additional postoperative EBRT, and 20 patients were previously irradiated. Results: The 5-year actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from metastatic disease of all patients was 64%, 28%, 40%, and 50%, respectively. The 5-year LC inside the IOERT field was 72%. For patients who completed IOERT and EBRT after R0-resection 5-year and 10-year OS was 80%, and 5-year and 10-year LC was 100%. Only 1 of the 21 patients after R0-resection and only 8 of 34 patients after R1-resection compared with 9 of 12 patients after R2-resection experienced inside IOERT–field relapse. Grade II or higher late complications were seen in 21% of the patients, but only 2 patients required surgical intervention because of late complications. Conclusion: In selected patients, IOERT results in excellent local control and survival, with acceptable morbidity. [Copyright &y& Elsevier]

• Primary lymphoma of bone is a rare entity with unspecific symptoms. • Typical radiology is a large soft-tissue tumor around non-destructed bone. • Treatment is based on systemic chemotherapy. • Chemotherapy seems to produce a better outcome than radiotherapy alone. • Positiv factors: age<60 y, solitary lesion, low LDH, favourable ECOG and IPI scores. Primary lymphoma of bone (PBL) is a rare entity. Due to unspecific clinical signs and equivocal radiographs diagnosis may be delayed. This retrospective report of 109 PBL cases demonstrates typical aspects of the lesion. Treatment and prognostic factors are evaluated. Retrospectively patient records were reviewed. All patients were followed for evidence of local or distant recurrence. Overall survival (OS) was used as clinical outcome. The median age of the 109 patients was 62.8 years. The most common symptoms were pain (76%), swelling (29%), neurologic symptoms and pathological fracture (16% each). Mean duration of symptoms was 8 months (0–197 months). 19% of patients had indolent NHL subtypes, 72% aggressive NHL subtypes and 7% cases Hodgkin disease. Cyclophosphamid, doxorubicin, vincristine and prednisone (CHOP) or CHOP plus rituximab (RCHOP) were given in 88 (81%) of patients. Radiotherapy was delivered in 67 (61%) of cases. 51 (47%) patients received both. Surgical interventions were restricted to cases with complications as fractures. The 5-year OS was 66%. The 5-year OS was 66%. In the subgroup of 78 patients with aggressive NHL subtype there was a highly significant benefit for chemotherapy or chemotherapy and radiation in comparison to no treatment or radiation alone. Raised LDH, age, IPI and ECOG performance were prognostic factors. In multivariate analysis, age and raised LDH levels only kept significance. In our series of primary bone lymphoma, chemotherapy resulted in a better outcome than Radiotherapy alone. Long-term survival is based on the stage of the disease, favoring younger (<60 years) patients with solitary bone lesions, low level of LDH and favourable ECOG performance status and IPI scores. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy (RT) is an integral part of the treatment of adult soft-tissue sarcomas (STS). Although mainly used as perioperative therapy to increase local control in resectable STS with high risk features, it also plays an increasing role in the treatment of non-resectable primary tumors, oligometastatic situations, or for palliation. This review summarizes the current evidence for RT in adult STS including typical indications, outcomes, side effects, dose and fractionation regimens, and target volume definitions based on tumor localization and risk factors. It covers the different overall treatment approaches including RT either as part of a multimodal treatment strategy or as a sole treatment and is accompanied by a summary on ongoing clinical research pointing at future directions of RT in STS. Radiation therapy (RT) is an integral part of the treatment of adult soft-tissue sarcomas (STS). Although mainly used as perioperative therapy to increase local control in resectable STS with high risk features, it also plays an increasing role in the treatment of non-resectable primary tumors, oligometastatic situations, or for palliation. Modern radiation techniques, like intensity-modulated, image-guided, or stereotactic body RT, as well as special applications like intraoperative RT, brachytherapy, or particle therapy, have widened the therapeutic window allowing either dose escalation with improved efficacy or reduction of side effects with improved functional outcome. This review summarizes the current evidence for RT in adult STS including typical indications, outcomes, side effects, dose and fractionation regimens, and target volume definitions based on tumor localization and risk factors. It covers the different overall treatment approaches including RT either as part of a multimodal treatment strategy or as a sole treatment, namely its use as an adjunct to surgery in resectable STS (perioperative RT), as a primary treatment in non-resectable tumors (definitive RT), as a local treatment modality in oligometastatic disease or as palliative therapy. Due to the known differences in clinical course, general treatment options and, consequently, outcome depending on lesion localization, the main part of perioperative RT is divided into three sections according to body site (extremity/trunk wall, retroperitoneal, and head and neck STS) including the discussion of special applications of radiation techniques specifically amenable to this region. The review of the current evidence is accompanied by a summary on ongoing clinical research pointing at future directions of RT in STS. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) is a mainstay for the treatment of lung cancer, but the effective dose is often limited by the development of radiation-induced pneumonitis and pulmonary fibrosis. Transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) play crucial roles in the development of these diseases, but the effects of dual growth factor inhibition on pulmonary fibrosis development remain unclear.Methods: C57BL/6 mice were treated with 20 Gy to the thorax to induce pulmonary fibrosis. PDGF receptor inhibitors SU9518 and SU14816 (imatinib) and TGFβ receptor inhibitor galunisertib were applied individually or in combinations after RT. Lung density and septal fibrosis were measured by high-resolution CT and MRI. Lung histology and gene expression analyses were performed and Osteopontin levels were studied.Results: Treatment with SU9518, SU14816 or galunisertib individually attenuated radiation-induced pulmonary inflammation and fibrosis and decreased radiological and histological signs of lung damage. Combining PDGF and TGFβ inhibitors showed to be feasible and safe in a mouse model, and dual inhibition significantly attenuated radiation-induced lung damage and extended mouse survival compared to blockage of either pathway alone. Gene expression analysis of irradiated lung tissue showed upregulation of PDGF and TGFβ-dependent signaling components by thoracic irradiation, and upregulation patterns show crosstalk between downstream mediators of the PDGF and TGFβ pathways.Conclusion: Combined small-molecule inhibition of PDGF and TGFβ signaling is a safe and effective treatment for radiation-induced pulmonary inflammation and fibrosis in mice and may offer a novel approach for treatment of fibrotic lung diseases in humans.Translational statement: RT is an effective treatment modality for cancer with limitations due to acute and chronic toxicities, where TGFβ and PDGF play a key role. Here, we show that a combined inhibition of TGFβ and PDGF signaling is more effective in attenuating radiation-induced lung damage compared to blocking either pathway alone. We used the TGFβ-receptor I inhibitor galunisertib, an effective anticancer compound in preclinical models and the PDGFR inhibitors imatinib and SU9518, a sunitinib analog. Our signaling data suggest that the reduction of TGFβ and PDGF signaling and the attenuation of SPP1 (Osteopontin) expression may be responsible for the observed benefits. With the clinical availability of similar compounds currently in phase-I/II trials as cancer therapeutics or already approved for certain cancers or idiopathic lung fibrosis (IPF), our study suggests that the combined application of small molecule inhibitors of TGFβ and PDGF signaling may offer a promising approach to treat radiation-associated toxicity in RT of lung cancer. [ABSTRACT FROM AUTHOR]

• Target delineation is crucial, but hampered by variability. • Variability in delineations will lead to differences in irradiated volumes and clinical outcome. • A key issue remains the delineation of clinically negative or elective lymph-nodal stations. • Guidelines (GL) available in literature are not consistent in their recommendations on anatomical boundaries. • This GL deals delineation of lymph-nodal involved in UGI for preoperative (or definitive) setting The European SocieTy for Radiation and Oncology -Advisory Committee on Radiation Oncology Practice (ESTRO-ACROP) endorsed a project to provide guidelines (GL) for the identification and delineation of clinically negative lymph-nodal stations (LNs) involved in upper gastrointestinal clinical scenarios. The presented GL is focused on preoperative (or definitive) setting. The project aim is to improve the consistency of clinical target volume (CTV) delineation by providing: a description of the anatomical boundaries of the LNs; a radiological computed tomography-based atlas depicting the LNs areas; a free, web-based, interactive example case for independent training of radiation oncologists on LNs delineation according to the presented GL, by both qualitative and quantitative analysis (through the FALCON EduCase platform). This project was carried out with the intention to facilitate and improve uniformity of future upper gastrointestinal guidelines on nodal CTV delineation. We report methodology and results from the collaboration of a working group panel selected by the ESTRO-ACROP. [ABSTRACT FROM AUTHOR]

• This guideline aims to help radiation oncologists to delineate target volumes for patients with ductal adenocarcinoma for conventionally fractionated and for stereotactic body radiotherapy. • Elective nodal areas are not recommended to be included for definitive treatment. • Consensus recommendations are given for adjuvant and neoadjuvant therapy ± the inclusion of nodal areas. • Organs of risk are defined and dose constraints are given. Despite of the predominant role of chemotherapy and surgery in pancreatic ductal adenocarcinoma (PDAC), radiotherapy (RT) still has a place in multimodal management of this disease where local tumour sequelae are fatal in about 40% of the patients. RT (chemoradiotherapy and stereotactic body radiotherapy) is used and investigated in the non-metastatic setting as part of definitive treatment strategies, in (neo)adjuvant settings and for locally recurrent disease. The ACROP committee was delegated by ESTRO to recommend target volume delineation for these clinical situations. The guidelines of this document are a result of a structured evaluation of the best available evidence by a panel of international experts in the field. Guidance for treatment planning including diagnostic imaging is provided. Recommendations are given for GTV delineation. The role and the definition of CTV volumes are critically discussed. Aspects of motion management and patient positioning are taken into account for PTV definition. Furthermore, aspects of delineation of organs at risk and of dose constraints are described in both, standard and hypofractionated, settings. This guideline has the purpose to support standardised and optimised processes of RT treatment planning for both, clinical practice and prospective studies. [ABSTRACT FROM AUTHOR]

• Radiation dose-escalation with IOERT feasible with limited toxicity to stomach, colon, kidneys and duodenum. • Abdominal pain improvement is a palliative effect observed after single high-dose electron irradiation. • Median survival time predominantly ranges from 8 to 12 months in electron boosted patients. • Long-term survivors with a low level of morbidity are reported in the context of small primary tumour size, use of systemic therapy and intraoperative radiation therapy. Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise sub-component of RT that can intensify the irradiation effect for cancer involving an anatomically well-defined volume, generally delivered with electrons (IOERT). Unresectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Long-term survivors were observed among unresected patients treated with external beam RT and an IOERT boost (OS 6% at 3 years; 3% >5 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted asset in the clinical scenario (maturity and reproducibility of results, albeit of low official level of evidence) and extremely accurate in terms of dose-deposit characteristics and normal tissue sparing. It is a technique that can be integrated with systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend the use of IOERT in cases of close surgical margins and residual disease. We report the ESTRO/ACROP recommendations for performing IOERT in unresected pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this retrospective outcome study was to validate the effectiveness of postoperative radiotherapy in breast conserving therapy (BCT) and to evaluate possible causes for omission of radiotherapy after breast conserving surgery (BCS) in a non-trial population. Methods Data were provided by the population-based Munich Cancer Registry. The study included epidemiological data of 30.811 patients diagnosed with breast cancer from 1998 to 2012. The effect of omitting radiotherapy was analysed using Kaplan–Meier-estimates and Cox proportional hazard regression. Variables predicting omission of radiotherapy were analysed using multivariate logistic regression. Results Use of postoperative radiotherapy after BCS was associated with significant improvements in local control and survival. 10-year loco-regional recurrence-free-survival was 90.8% with postoperative radiotherapy vs. 77.6% with surgery alone ( p < 0.001). 10-year overall survival rates were 55.2% with surgery alone vs. 82.2% following postoperative radiotherapy ( p < 0.001). Variables predicting omission of postoperative radiotherapy included advanced age (women ⩾80 years; OR: 0.082; 95% CI: 0.071–0.094, p < 0.001). Conclusions This study shows a decrease in local control and a survival disadvantage if postoperative radiotherapy after breast conserving surgery is omitted in an unselected cohort of primary breast cancer patients. Due to its epidemiological nature, it cannot answer the question in whom postoperative radiotherapy can be safely omitted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the local positioning uncertainties during fractionated radiotherapy of head-and-neck cancer patients immobilized using a custom-made fixation device and discuss the effect of possible patient correction strategies for these uncertainties. Methods and Materials: A total of 45 head-and-neck patients underwent regular control computed tomography scanning using an in-room computed tomography scanner. The local and global positioning variations of all patients were evaluated by applying a rigid registration algorithm. One bounding box around the complete target volume and nine local registration boxes containing relevant anatomic structures were introduced. The resulting uncertainties for a stereotactic setup and the deformations referenced to one anatomic local registration box were determined. Local deformations of the patients immobilized using our custom-made device were compared with previously published results. Several patient positioning correction strategies were simulated, and the residual local uncertainties were calculated. Results: The patient anatomy in the stereotactic setup showed local systematic positioning deviations of 1–4 mm. The deformations referenced to a particular anatomic local registration box were similar to the reported deformations assessed from patients immobilized with commercially available Aquaplast masks. A global correction, including the rotational error compensation, decreased the remaining local translational errors. Depending on the chosen patient positioning strategy, the remaining local uncertainties varied considerably. Conclusions: Local deformations in head-and-neck patients occur even if an elaborate, custom-made patient fixation method is used. A rotational error correction decreased the required margins considerably. None of the considered correction strategies achieved perfect alignment. Therefore, weighting of anatomic subregions to obtain the optimal correction vector should be investigated in the future. [Copyright &y& Elsevier]

Purpose: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). Methods and Materials: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40–50.4 Gy) in conventional fractionation (1.8–2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. Results: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2–4 was observed in 23% and late toxicity Grade 2–4 in 17% of patients. Conclusions: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma. [Copyright &y& Elsevier]

Purpose: Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. Methods and Materials: The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. Results: After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Conclusions: Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients. [Copyright &y& Elsevier]