Search

Abstract Purpose The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers. Methods In this cross-sectional case-based survey study, 5 anonymized patient cases with imaging data of localized STS were presented to MTBs of 21 German-speaking tertiary referral hospitals. Centers provided recommendations on treatment sequence and modalities, along with the consensus level within their MTB. Agreement percentages were calculated, and consensus levels were rated on a scale of 1 to 10. Results Five patient cases were discussed resulting in 105 recommendations. Agreement percentages for case 1 to 5 were 14.3%, 61.9%, 33.3%, 52.4% and 9.3%, with a median agreement percentage of 33.3%. Grouping pre- and postoperative therapies as "perioperative" and including recommendations with and without regional hyperthermia raised the median agreement to 47.6%. The mean consensus level within each center across all 5 cases was 9.5. Conclusion This first case-based analysis of inter-center agreement for STS management in German-speaking countries reveals low inter-center agreement but high intra-center consensus. Our study includes nearly all tertiary sarcoma centers in German-speaking countries, affirming its strong external validity. These findings suggest potential and clinically very relevant differences in treatment standards among sarcoma centers. Enhanced case-based exchanges and collaborative efforts are needed to reduce discrepancies and standardize the management of STS patients.

Purpose To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials.Methods In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT.Results We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40–43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry.Discussion There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects.Conclusions The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Purpose: Addressing the epidermal growth factor receptor (EGFR)-pathway by the competitive receptor ligand cetuximab is a promising strategy in pancreatic cancer. In the prospective randomized controlled phase II PARC-study (PARC: Pancreatic cancer treatment with radiotherapy (RT) and cetuximab), we evaluated safety and efficacy of a trimodal treatment scheme consisting of cetuximab, gemcitabine and RT in locally advanced pancreatic cancer (LAPC). Methods: Between January 2005 and April 2007, 68 patients with inoperable pancreatic ductal adenocarcinoma were randomized in either trimodal therapy followed by gemcitabine maintenance (Arm A) or in trimodal therapy followed by gemcitabine plus cetuximab maintenance (Arm B). Intensity-modulated RT (IMRT) was performed with a total dose of 45 Gy in 25 fractions and with a simultaneous integrated boost to the gross tumor (54 Gy). Within the trimodal therapy, gemcitabine and cetuximab were administered weekly. Maintenance therapy consisted of gemcitabine only or gemcitabine plus cetuximab. Toxicity, overall survival (OS), secondary resection rate, local control and progression free survival (PFS) were evaluated. Results: With a median followup time of 13 months (range: 2 – 184 months), one patient is still alive and one patient is lost to follow-up. Nausea and gastrointestinal hemorrhage were the most important higher-graded (>°II) acute and late non-hematological toxicity (13% and 7%). Median OS was 13.1 months without significant difference between both treatment arms (Arm A: 11.9 months; Arm B: 14.2 months). Compared to historical data, cetuximab did not improve OS. One- and two-year local control rates were 76.6% and 68.9%. Local tumor control and secondary resection rate (Arm A: 4%; Arm B: 16%) were significantly improved in Arm B. Median PFS was 6.8 months with distant metastasis as main treatment failure. Conclusion: Trimodal therapy consisting of IMRT, gemcitabine and cetuximab can be considered safe and feasible. Compared to historical data, cetuximab does not improve treatment efficacy in LAPC patients treated with chemoradiation.

Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable 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. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 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 approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer.

Abstract Background Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. Methods This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. Discussion The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. Trial registration The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419 . “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”. Study status Ongoing study. Start of recruitment was December 2019.

SummaryPurpose??We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite ? poly(ADPribose) polymerase (PARP) pathway in inflammatory response and apoptosis induction after vascular gamma irradiation.Methods??Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or 20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10). Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n = 10) to distinguish between primary effects of vascular injury and secondary effects due to irradiation.Results??After 21 days, neointima formation was significantly suppressed after irradiation (control: 0.07 mm2? 0.04 mm2, 15 Gy: 0.003 mm2? 0.004 mm2, 20 Gy: 0.001 mm2? 0.0006 mm2,PP= 0.003). Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups.Conclusion??Activation of the peroxynitrite-PARP pathway was demonstrated during neointima proliferation in a rat model of surgical vascular injury. Vascular irradiation suppressed neointima formation, but induced significant activation of the peroxynitrite ? PARP pathway in the outer vessel wall layers concomitant to inflammation and focal wall necrosis. This may contribute to adverse effects of vascular irradiation such as fibrosis and constrictive remodeling. [ABSTRACT FROM AUTHOR]