Patient-Relevant Costs for Organ Preservation versus Radical Resection in Locally Advanced Rectal Cancer.

Total neoadjuvant therapy (TNT) is an evolving treatment schedule for locally advanced rectal cancer (LARC), allowing for organ preservation in a relevant number of patients in the case of complete response. Patients who undergo this so-called "watch and wait" approach are likely to benefit regarding their quality of life (QoL), especially if definitive ostomy could be avoided. In this work, we performed the first cost-effectiveness analysis from the patient perspective to compare costs for TNT with radical resection after neoadjuvant chemoradiation (CRT) in the German health care system. Individual costs for patients insured with a statutory health insurance were calculated with a Markov microsimulation. A subgroup analysis from the prospective "FinTox" trial was used to calibrate the model's parameters. We found that TNT was less expensive (-1540 EUR) and simultaneously resulted in a better QoL (+0.64 QALYs) during treatment and 5-year follow-up. The average cost for patients under TNT was 4711 EUR per year, which was equivalent to 3.2% of the net household income. CRT followed by resection resulted in higher overall costs for ostomy care, medication and greater loss of earnings. Overall, TNT appeared to be more efficacious and cost-effective from a patient's point of view in the German health care system.

Satisfaction with radiotherapy care among cancer patients treated in Germany-secondary analysis of a large multicenter study.

PURPOSE: Patient satisfaction with healthcare has been linked to clinical outcomes and regulatory agencies demand its regular assessment. Therefore, we aimed to investigate patient satisfaction with radiotherapy care and its determinants. METHODS: This is a secondary analysis of a multicenter prospective cross-sectional study. Eligible cancer patients anonymously completed questionnaires at the end of a course of radiotherapy. The outcome variable was overall patient satisfaction with radiotherapy care measured with a 10-point Likert scaled single-item. Given patient satisfaction was defined for patients scoring ≥ 8 points. Determinants of given patient satisfaction were assessed by univariable and multivariable analyses. A p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 eligible patients, 1075 participated (participation rate 46%). Data on patient satisfaction was provided by 1054 patients. There was a right-skewed distribution towards more patient satisfaction (mean = 8.8; SD = 1.68). Given patient satisfaction was reported by 85% (899/1054) of the patients. Univariable analyses revealed significant associations of lower patient satisfaction with tumor entity (rectal cancer), concomitant chemotherapy, inpatient care, treating center, lower income, higher costs, and lower quality of life. Rectal cancer as tumor entity, treating center, and higher quality of life remained significant determinants of patient satisfaction in a multivariable logistic regression. CONCLUSION: Overall patient satisfaction with radiotherapy care was high across 11 centers in Germany. Determinants of patient satisfaction were tumor entity, treating center, and quality of life. Although these data are exploratory, they may inform other centers and future efforts to maintain high levels of patient satisfaction with radiotherapy care.

Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort.

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.

Psychosocial distress in cancer patients undergoing radiotherapy: a prospective national cohort of 1042 patients in Germany.

PURPOSE: Psychosocial distress is common among cancer patients in general, but those undergoing radiotherapy may face specific challenges. Therefore, we investigated the prevalence and risk factors for distress in a large national cohort. METHODS: We performed a secondary analysis of a multicenter prospective cross-sectional study which surveyed cancer patients at the end of a course of radiotherapy using a patient-reported questionnaire. Distress was measured with the distress thermometer (DT), using a cut-off of ≥ 5 points for clinically significant distress. Univariate analyses and multivariate multiple regression were used to assess associations of distress with patient characteristics. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 potentially eligible patients, 1075 participated in the study, of which 1042 completed the DT. The median age was 65 years and 49% (511/1042) of patients were female. The mean DT score was 5.2 (SD = 2.6). Clinically significant distress was reported by 63% (766/1042) of patients. Of the patient characteristics that were significantly associated with distress in the univariate analysis, a lower level of education, a higher degree of income loss, lower global quality of life, and a longer duration of radiotherapy in days remained significantly associated with higher distress in the multivariate analysis. Yet effect sizes of these associations were small. CONCLUSION: Nearly two in three cancer patients undergoing radiotherapy reported clinically significant distress in a large multicenter cohort. While screening and interventions to reduce distress should be maintained and promoted, the identified risk factors may help to raise awareness in clinical practice. TRIAL REGISTRY IDENTIFIER: DRKS: German Clinical Trial Registry identifier: DRKS00028784.

Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO).

INTRODUCTION: Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions. METHODS: PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses. DISCUSSION: Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies.

Development, implementation, and results of a simulation-based hands-on brachytherapy workshop for medical students.

PURPOSE: The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) require the development of competence-oriented teaching formats. In addition, there is a great need for high-quality teaching in the field of radiation oncology, which manifests itself already during medical school. For this reason, we developed a simulation-based, hands-on medical education format to teach competency in performing accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy for early breast cancer. In addition, we designed realistic breast models suitable for teaching both palpation of the female breast and implantation of brachytherapy catheters. METHODS: From June 2021 to July 2022, 70 medical students took part in the hands-on brachytherapy workshop. After a propaedeutic introduction, the participants simulated the implantation of single-lead catheters under supervision using the silicone-based breast models. Correct catheter placement was subsequently assessed by CT scans. Participants rated their skills before and after the workshop on a six-point Likert scale in a standardized questionnaire. RESULTS: Participants significantly improved their knowledge-based and practical skills on APBI in all items as assessed by a standardized questionnaire (mean sum score 42.4 before and 16.0 after the course, p < 0.001). The majority of respondents fully agreed that the workshop increased their interest in brachytherapy (mean 1.15, standard deviation [SD] 0.40 on the six-point Likert scale). The silicone-based breast model was found to be suitable for achieving the previously defined learning objectives (1.19, SD 0.47). The learning atmosphere and didactic quality were rated particularly well (mean 1.07, SD 0.26 and 1.13, SD 0.3 on the six-point Likert scale). CONCLUSION: The simulation-based medical education course for multicatheter brachytherapy can improve self-assessed technical competence. Residency programs should provide resources for this essential component of radiation oncology. This course is exemplary for the development of innovative practical and competence-based teaching formats to meet the current reforms in medical education.

Financial toxicity in cancer patients undergoing radiotherapy in a universal health care system - A prospective multicenter study of 1075 patients.

PURPOSE: To establish and confirm prevalence as well as risk factors of financial toxicity in a large national cohort of cancer patients undergoing radiotherapy in a universal health care system. METHODS: We conducted a prospective cross-sectional study offering a patient-reported questionnaire to all eligible cancer patients treated with radiotherapy in 11 centers in Germany during 60 consecutive days. The four-point subjective financial distress question of the EORTC QLQ-C30 was used as a surrogate for financial toxicity. Confirmatory hypothesis testing evaluated the primary study outcomes: overall prevalence of financial toxicity and its association with predefined risk factors. P-values < 0.05 were considered statistically significant. RESULTS: Of 2341 eligible patients, 1075 (46%) participated. The prevalence of subjective financial distress (=any grade higher than not present) was 41% (438/1075) exceeding the hypothesized range of 26.04-36.31%. Subjective financial distress was felt "A little" by 26% (280/1075), "Quite a bit" by 11% (113/1075) and "Very much" by 4% (45/1075) of the patients. Lower household income, lower global health status/ quality of life, higher direct costs and higher loss of income significantly predicted higher subjective financial distress per ordinal regression and confirmed these risk factors. Higher psychosocial distress and lower patient satisfaction were significantly associated with higher subjective financial distress in an exploratory ordinal regression model. CONCLUSION: The overall prevalence of financial toxicity was higher than anticipated, although reported at low or moderate degrees by most affected patients. As we confirmed risk factors associated with financial toxicity, patients at risk should be addressed early for potential support.

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation.

Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T2 * magnetic resonance (MR) relaxometry is a more accurate alternative for follow-up in pediatric patients before and after allogenic SCT. Twenty-three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T2 * relaxometry on a 1.5 T MR-scanner to estimate liver iron concentrations from the T2 * values ("MR-Fe"). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR-Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR-Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR-Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.

Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions.

BACKGROUND: Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE: The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS: ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS: We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION: Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.