Radiotherapy for Colorectal Cancer: Current Standards and Future Perspectives

Background: Multimodal treatment approaches are indispensable for patients with advanced-stage colorectal cancer. Radiotherapy has been established as essential part of perioperative concepts and was introduced as an option to face challenges such as local relapse or oligometastases. Methods: A literature review was performed to summarize evidence and current standards of radiotherapeutic concepts in the treatment of colorectal cancer. Results: For stage II/III rectal cancer, neoadjuvant radiotherapy is superior to adjuvant treatment. Two preoperative regimens have been established and are commonly used with different objectives: short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT). Both reduce the risk of local relapse. Additionally, LC-CRT aims at downsizing the tumor to potentially reduce radicalness of surgery. There is increasing evidence that not all stage II/III rectal cancer patients need neoadjuvant irradiation but also that in some cases surgery might be omitted. Stereotactic body radiotherapy (SBRT) of the liver shows high rates of local control in oligometastatic patients. Intraoperative and particle radiotherapy extend the spectrum of treatment options for locally recurrent patients. Conclusion: Radiotherapeutic concepts are crucial for the primary management of locally advanced colorectal cancer and can essentially contribute to treatment approaches in locally recurrent, oligometastatic or palliative patients

Intrafractional dose variation and beam configuration in carbon ion radiotherapy for esophageal cancer

Background: In carbon ion radiotherapy (CIR) for esophageal cancer, organ and target motion is a major challenge for treatment planning due to potential range deviations. This study intends to analyze the impact of intrafractional variations on dosimetric parameters and to identify favourable settings for robust treatment plans. Methods: We contoured esophageal boost volumes in different organ localizations for four patients and calculated CIR-plans with 13 different beam geometries on a free-breathing CT. Forward calculation of these plans was performed on 4D-CT datasets representing seven different phases of the breathing cycle. Plan quality was assessed for each patient and beam configuration. Results: Target volume coverage was adequate for all settings in the baseline CIR-plans (V95 > 98% for two-beam geometries, > 94% for one-beam geometries), but reduced on 4D-CT plans (V95 range 50–95%). Sparing of the organs at risk (OAR) was adequate, but range deviations during the breathing cycle partly caused critical, maximum doses to spinal cord up to 3.5x higher than expected. There was at least one beam configuration for each patient with appropriate plan quality. Conclusions: Despite intrafractional motion, CIR for esophageal cancer is possible with robust treatment plans when an individually optimized beam setup is selected depending on tumor size and localization

Acute Toxicity and Early Oncological Outcomes After Intraoperative Electron Radiotherapy (IOERT) as Boost Followed by Whole Breast Irradiation in 157 Early Stage Breast Cancer Patients—First Clinical Results From a Single Center

Introduction: Breast conserving surgery (BCS) followed by postoperative whole breast irradiation (WBI) is the current standard of care for early stage breast cancer patients. Boost to the tumor bed is recommended for patients with a higher risk of local recurrence and may be applied with different techniques. Intraoperative electron radiotherapy (IOERT) offers several advantages compared to other techniques, like direct visualization of the tumor bed, better skin sparing, less inter- and intrafractional motion, but also radiobiological effects may be beneficial. Objective of this retrospective analysis of IOERT as boost in breast cancer patients was to assess acute toxicity and early oncological outcomes.Material and Methods: All patients, who have been irradiated between 11/2014 and 01/2018 with IOERT during BCS were analyzed. IOERT was applied using the mobile linear accelerator Mobetron with a total dose of 10 Gy, prescribed to the 90% isodose. After ensured woundhealing, WBI followed with normofractionated or hypofractionated regimens. Patient reports, including diagnostic examinations and toxicity were analyzed after surgery and 6–8 weeks after WBI. Overall survival, distant progression-free survival, in-breast and contralateral breast local progression-free survival were calculated using the Kaplan-Meier method. Furthermore, recurrence patterns were assessed.Results: In total, 157 patients with a median age of 57 years were evaluated. Postoperative adverse events were mild with seroma and hematoma grade 1–2 in 26% and grade 3 in 0.6% of the patients. Wound infections grade 2–3 occurred in 2.2% and wound dehiscence grade 1–2 in 1.9% of the patients. Six to eight weeks after WBI radiotherapy-dependent acute dermatitis grade 1–2 was most common in 90.9% of the patients. Only 4.6% of the patients suffered from dermatitis grade 3. No grade 4 toxicities were documented after surgery or WBI. 2- and 3-year overall survival and distant progression-free survival, were 97.5 and 93.6, and 0.7 and 2.8%, respectively. In-breast recurrence and contralateral breast cancer rates after 3 years were 1.9 and 2.8%, respectively.Conclusion: IOERT boost during BCS is a safe treatment option with low acute toxicity. Short-term recurrence rates are comparable to previously published data and emphasize, that IOERT as boost is an effective treatment

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Individual 3D-printed fixation masks for radiotherapy: first clinical experiences

Purpose!#!To show the feasibility of 3D-printed fixation masks for whole brain radiation therapy in a clinical setting and perform a first comparison to an established thermoplastic mask system.!##!Methods!#!Six patients were irradiated with whole brain radiotherapy using individually 3D-printed masks. Daily image guidance and position correction were performed prior to each irradiation fraction. The vectors of the daily position correction were compared to two collectives of patients, who were irradiated using the standard thermoplastic mask system (one cohort with head masks; one cohort with head and neck masks).!##!Results!#!The mean systematic errors in the experimental cohort ranged between 0.59 and 2.10 mm which is in a comparable range to the control groups (0.18 mm-0.68 mm and 0.34 mm-2.96 mm, respectively). The 3D-printed masks seem to be an alternative to the established thermoplastic mask systems. Nevertheless, further investigation will need to be performed.!##!Conclusion!#!The prevailing study showed a reliable and reproducible interfractional positioning accuracy using individually 3D-printed masks for whole brain irradiation in a clinical routine. Further investigations, especially concerning smaller target volumes or other areas of the body, need to be performed before using the system on a larger basis

Simultaneous integrated boost for adjuvant treatment of breast cancer- intensity modulated vs. conventional radiotherapy: The IMRT-MC2 trial

Abstract Background Radiation therapy is an essential modality in the treatment of breast cancer. Addition of radiotherapy to surgery has significantly increased local control and survival rates of the disease. However, radiotherapy is also associated with side effects, such as tissue fibrosis or enhanced vascular morbidity. Modern radiotherapy strategies, such as intensity modulated radiotherapy (IMRT), can shorten the overall treatment time by integration of the additional tumor bed boost significantly. To what extent this might be possible without impairing treatment outcome and cosmetic results remains to be clarified. Methods/Design The IMRT-MC2 study is a prospective, two armed, multicenter, randomized phase-III-trial comparing intensity modulated radiotherapy with integrated boost to conventional radiotherapy with consecutive boost in patients with breast cancer after breast conserving surgery. 502 patients will be recruited and randomized into two arms: patients in arm A will receive IMRT in 28 fractions delivering 50.4 Gy to the breast and 64.4 Gy to the tumor bed by integrated boost, while patients in arm B will receive conventional radiotherapy of the breast in 28 fractions to a dose of 50.4 Gy and consecutive boost in 8 fractions to a total dose of 66.4 Gy. Discussion Primary objectives of the study are the evaluation of the cosmetic results 6 weeks and 2 years post treatment and the 2- and 5-year local recurrence rates for the two different radiotherapy strategies. Secondary objectives are long term overall survival, disease free survival and quality of life. Trial Registration ClinicalTrials.gov Protocol ID: NCT01322854.</p

Predisposing factors for early retirement in patients with Schizophrenia in Germany

Schizophrenia, Early retirement, Predisposing factor, Costs, Pension fund,