Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

Purpose To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiotherapy for prostate cancer, and to assess for factors correlated with rectal dose reduction. Materials and methods Fifty-two patients at 4 institutions were enrolled onto a prospective pilot clinical trial. Patients underwent baseline scans, then were injected with perirectal spacing hydrogel and re-scanned. IMRT plans were created on both scans for comparison. Objectives were to establish rates of creation of ≥7.5mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed to evaluate associations between pre- vs. post-injection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, PTV volume, as well as post-injection mid-gland separation, gel volume, gel thickness, length of PTV/gel contact, or gel left-to-right symmetry. Results Hydrogel resulted in ≥ 7.5mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with mean reduction of 8.0 Gy. There were no significant differences in pre- and post-injection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different pre- vs. post-injection (P = 0.02); plans with worse conformity indexes post-injection compared to pre-injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater post-injection reduction in V70 was associated with decreased relative post-injection plan conformity (P=0.01). Reductions in V70 did not significantly vary by institution, despite significant inter-institutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. Conclusions Injection of hydrogel into prostate-rectal interface resulted in dose reductions to rectum for > 90% of patients treated. Rectal sparing was statistically significant across a range of 10–75 Gy, and was demonstrated within the presence of significant inter-institutional variability in plan conformity, target definitions, and injection results.

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;120:3410-7.

BACKGROUND:The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS: Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in raster scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Longterm toxicity was quantitatively assessed using questionnaires. RESULTS: The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age 45 years and boost volume 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS: Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009. Cancer 2014;120:1579-85.

No abstract

Background Primary adenoid cystic carcinomas (ACCs) of the trachea are rare tumors of the central bronchial system. In patients presenting with unresectable tumors, severe comorbidities, or incomplete surgical resection, definitive radiotherapy is currently the recommended treatment. Irradiation with carbon ions (C 12 ) has shown promising local control (LC) and survival rates in cases of ACCs of the head and neck. No data on the therapeutic efficacy of C12 radiotherapy in treating tracheal ACC has been published. Methods All patients with histologically confirmed ACC of the trachea treated with surgery and/or radiation treatment at Heidelberg University Hospital between 1991 and 2017 were included in this analysis. Patient and treatment characteristics, short- and long-term toxicity after radiotherapy, overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) were prospectively acquired and retrospectively analyzed. Results Thirty-eight patients (23 women and 15 men) with a median age of 51 were treated by surgery ( n = 20) and/or radiotherapy with either C 12 ( n = 7) or photons ( n = 24). Of these patients, 61% presented with locally advanced (stage 4) ACC. The median follow-up for all patients was 74.5 months. The 5-year OS for all patients was 95% (10-year: 81%). The 5-year FFLP and FFDP were 96% (10-year: 83%) and 69% (10-year: 53%), respectively. In patients who underwent surgery alone, the 5-year OS was 100% (10-year: 80%). The 5-year FFLP and FFDP were 100% (10-year: 100%) and 80% (10-year: 60%), respectively. In patients who underwent radiotherapy alone, the 5-year OS was 100% (10-year: 83%). The 5-year FFLP and FFDP were 88% (10-year: 44%) and 67% (10-year: 34%), respectively. In patients who received multi-modal treatment including surgery and adjuvant radiotherapy, the 5-year OS was 84% (10-year: 84%). The 5-year FFLP was 100% (10-year: 100%) and the 5-year FFDP was 65% (10-year, 65%). Conclusions The long-term prognosis is favorable if surgery is performed. In cases of an incomplete resection, good OS can still be achieved following adjuvant radiotherapy. For radiotherapy, irradiation with C 12 shows promising first results. However, more data is needed to prove the long-term advantage of C 12 over photons. Trial registration The ethics committee of the Heidelberg University Hospital approved the retrospective data analysis (S-174/2019).

No abstract

BackgroundRadiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial.MethodsFifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).ResultsOf the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months.ConclusionThe use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.