Explore the vast range of titles available.

PurposeBreast cancer patients receive treatment recommendations from multidisciplinary tumour boards. To determine the consequences of patients’ refusal of such recommendations, we analysed the database of the Centre for Breast Cancer at the Ortenau Clinic in Offenburg, Germany.MethodsA total of 4315 patients with non-metastatic primary breast cancer, treated between 1997 and 2019, were analysed with descriptive analyses, Kaplan–Meier survival analyses, and Cox regression analyses regarding the effects of their refusal.ResultsAbout 10.7% of the patients rejected the treatment advice. These were significantly elderly (F = 74.4; p < 0.001; one-way ANOVA), with greater tumour size (F = 36.7; p < 0.001; one-way ANOVA), a higher number of affected lymph nodes (F = 4.2; p = .039; one-way ANOVA), and more poorly differentiated tumours (χ2 = 16.8; df = 2; p < 0.001). The refusal of adjuvant treatment resulted in higher rates of local recurrences (χ2radiotherapy = 109.1; df = 1; p < 0.001, χ2chemotherapy = 18.3; df = 1; p < 0.001, χ2endocrine = 32.5; df = 1; p < 0.001) and poorer overall survival (χ2radiotherapy = 184.9; df = 6; p < 0.001; χ2chemotherapy = 191.8; df = 6; p < 0.001).ConclusionsAll parts of the adjuvant treatment of breast cancer are clearly associated with improvements regarding disease-free and overall survival. To answer open questions about the background of patients’ refusal, an analysis of prospective data collections seems necessary. In addition, patient communication should be improved so that patients understand the background of the multidisciplinary tumour board and the potential consequences of their refusal.

Xerostomia is an important chronic side effect of radiotherapy in the head and neck area. The authors investigated the efficacy of different artificial saliva compounds in patients with postirradiation xerostomia. In 120 patients with xerostomia after radiotherapy for head and neck cancer, four different saliva substitute compounds (gel, carmellose spray, oil, mucin spray) were tested in a prospective crossover design. Xerostomia at baseline and under treatment with each compound was measured with a questionnaire approved in a pilot trial. All compounds significantly improved xerostomia when compared to baseline situation (p < 0.0001). The gel was rated best, the carmellose spray was rated worst by the patients, but the single compounds did not differ significantly in their effects. In spite of this result, most patients chose the carmellose spray as their favorite compound. This is due to its good taste and easy handling, which play an important role for the acceptance of the products. Big individual differences in the preference of the single compounds were found. For most patients considerable relief from xerostomia can be reached by saliva substitutes. Thus, every patient with xerostomia should be given different artificial saliva compounds for a test period. This will help to find the individually best way to cope with the dry mouth.

Background Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. Patients and methods SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. Results The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. Conclusion With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Background A basis for future trials with stereotactic body radiotherapy (SBRT) for tumors of the liver hilum should be established. Thus, dosage concepts, planning processes, and dose constraints as well as technical innovations are summarized in this contribution. Methods On the background of our own data, the current literature was reviewed. The use of SBRT in the most common tumors of the liver hilum (pancreatic cancer and Klatskin tumors) was investigated. Dose constraints were calculated in 2 Gy standard fractionation doses. Results A total of 8 pilot or phase I/II studies about SBRT in the liver hilum were identified. In recent years, the SBRT technique has developed very quickly from classical stereotactic body frame radiotherapy to IGRT techniques including gating and tracking systems. In the studies using classical body frame technique, patients experienced considerable toxicities (duodenal ulcer/perforation) as compared to tolerable side effects in IGRT studies (<10% grade 3 and 4 toxicities). Dose constraints for duodenum, liver, kidneys, colon, and spinal cord were derived from the investigated studies. Survival and local tumor control data are very heterogeneous: median survival in these patients with locally advanced pancreatic or Klatskin tumors ranges between 5 and 32 months. Excellent local tumor control rates of about 80% over 24 months were achieved using SBRT. Conclusion Despite a few negative results, SBRT seems to be a promising technique in the treatment of tumors of the liver hilum. Highest precision in diagnostics, positioning, and irradiation as well as strict dose constraints should be applied to keep target volumes as small as possible and side effects tolerable.

At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT00697333. From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5–21] vs 29% [17–38] at 1 year; HR 0·57 [95% CI 0·30–1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9–24] vs 30% [20–39] at 1 year; HR 0·64 [95% CI 0·37–1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. German Cancer Aid (Deutsche Krebshilfe).

A basis for future trials with stereotactic body radiotherapy (SBRT) for tumors of the liver hilum should be established. Thus, dosage concepts, planning processes, and dose constraints as well as technical innovations are summarized in this contribution. On the background of our own data, the current literature was reviewed. The use of SBRT in the most common tumors of the liver hilum (pancreatic cancer and Klatskin tumors) was investigated. Dose constraints were calculated in 2 Gy standard fractionation doses. A total of 8 pilot or phase I/II studies about SBRT in the liver hilum were identified. In recent years, the SBRT technique has developed very quickly from classical stereotactic body frame radiotherapy to IGRT techniques including gating and tracking systems. In the studies using classical body frame technique, patients experienced considerable toxicities (duodenal ulcer/perforation) as compared to tolerable side effects in IGRT studies (<10% grade 3 and 4 toxicities). Dose constraints for duodenum, liver, kidneys, colon, and spinal cord were derived from the investigated studies. Survival and local tumor control data are very heterogeneous: median survival in these patients with locally advanced pancreatic or Klatskin tumors ranges between 5 and 32 months. Excellent local tumor control rates of about 80% over 24 months were achieved using SBRT. Despite a few negative results, SBRT seems to be a promising technique in the treatment of tumors of the liver hilum. Highest precision in diagnostics, positioning, and irradiation as well as strict dose constraints should be applied to keep target volumes as small as possible and side effects tolerable.[PUBLICATION ABSTRACT]

•Among breast cancer patients undergoing radiotherapy Vitamin D deficiency is common.•We found no correlation between skin toxicity, vitamin D and selenium blood levels.•Skin toxicities correlated significantly with breast size and skin thickness. Vitamin D blood levels have been shown to influence acute chemotherapy toxicities. Therefore, it was investigated whether it is an intrinsic factor influencing acute skin toxicity in patients receiving radiotherapy for breast cancer. In a total of 107 patients receiving radiotherapy for resected breast cancer, vitamin D and selenium blood levels were determined. Correlations between these levels and skin toxicity due to radiotherapy (CTC scores, Skindex scores) were investigated as primary endpoints. Furthermore, the statistical relationship between skin toxicity, vitamin D and selenium blood levels with patient and disease characteristics such as tumor stage, breast size, skin thickness, blood cell counts as well as individual quality of life measured by SEIQoL-Q was analyzed. In our patient collective large deficiencies of vitamin D (mean level 20.9 ng/ml, normal range 36–60 ng/ml) and selenium (mean level 76.1 μg/l, normal range 74–139 μg/l) were found. No correlations between skin toxicities, vitamin D and selenium blood levels were found. Neither did these blood levels correlate with any tumor or patient characteristics nor with individual quality of life. As expected by clinical experience, skin toxicities correlated significantly with breast size and skin thickness. In this study, radiotherapy skin toxicity was not influenced by vitamin D or selenium blood levels. On the basis of our data we cannot recommend vitamin D or selenium supplementation as a prophylaxis for skin toxicity. Nevertheless, large numbers of breast cancer patients have substantial deficiencies of both substances. Therefore, supplementation may be reasonable for other reasons.

Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3–4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m2 days 1–5 and 29–33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m2 days 1–5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (250 mg/m2 days 1–14 and 22–35) and oxaliplatin (50 mg/m2 days 1, 8, 22, and 29), followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin (100 mg/m2 days 1 and 15), leucovorin (400 mg/m2 days 1 and 15), and infusional fluorouracil (2400 mg/m2 days 1–2 and 15–16; fluorouracil plus oxaliplatin group). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1–4 vs cT4), and clinical N category (cN0 vs cN1–2) without masking. DFS is the primary endpoint. Secondary endpoints, including toxicity, compliance, and histopathological response are reported here. Safety and compliance analyses included patients as treated, efficacy endpoints were analysed according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT00349076. Of the 1265 patients initially enrolled, 1236 were evaluable (613 in the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group). Preoperative grade 3–4 toxic effects occurred in 140 (23%) of 606 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy. Grade 3–4 diarrhoea was more common in those who received fluorouracil and oxaliplatin during chemoradiotherapy than in those who received fluorouracil during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3–4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495 (79%) and 601 (96%) of 624 patients who received fluorouracil-based chemoradiotherapy, respectively. A pathological complete response was achieved in 103 (17%) of 591 patients who underwent surgery in the fluorouracil and oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the fluorouracil group (odds ratio 1·40, 95% CI 1·02–1·92; p=0·038). In the fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant chemotherapy completed all cycles (with or without dose reduction), as did 386 (83%) of 463 patients in the fluorouracil group. Inclusion of oxaliplatin into modified fluorouracil-based combined modality treatment was feasible and led to more patients achieving a pathological complete response than did standard treatment. Longer follow-up is needed to assess DFS. German Cancer Aid (Deutsche Krebshilfe).

Low anterior resection (LAR) and abdominoperineal resection (APR) are the two main surgical procedures after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. APR is associated with poorer prognosis; however existing data do not consider intensified CRT (5-Fluorouracil (5-FU)/Oxaliplatin + radiation) protocols. Clinicopathological data of patients treated with APR and LAR from the CAO/ARO/AIO-04 trial were analysed in terms of prognostic parameters and quality of life (QoL). Based on higher response rate after intensified CRT, subgroup analyses were performed. Data from n  = 1173 patients were assessed. APR after preoperative CRT was associated with a significantly worse overall survival ( p  = 0.0056), disease-free survival ( p  < 0.0001) and local recurrence rate ( p  = 0.0047). Clinicopathological data including clinical T stage ( p  < 0.000001), grading ( p  = 0.0038), postoperative lymph node (LN) positivity ( p  = 0.013), and number of positive LN ( p  = 0.0049) significantly differed between procedures and showed higher values in APR patients. The quality of total mesorectal excision (TME) was significantly better ( p  < 0.0001) and complete resection rates were higher ( p  = 0.0022) in LAR compared to APR patients. Subgroup analyses showed worse LR rates in APR patients after standard CRT (5-FU mono and radiation) but not after intensified CRT. After 3 years, role functioning ( p  = 0.019) and physical functioning ( p  = 0.001) had a slightly poorer outcome in APR patients. The poorer prognosis of patients undergoing APR for locally advanced rectal cancer may be explained by clinicopathological characteristics. Intensified CRT may compensate for the higher risk of LR after APR in patients with worse TME quality. QoL in APR patients was comparable to LAR patients.