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Background/Objectives : Definitive radiochemotherapy with concomitant cisplatin 40 mg/m 2 weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy. Methods : We retrospectively analyzed 147 patients, who received definitive radiochemotherapy between 2000 and 2019 and evaluated laboratory parameters before, after, and at each chemotherapy cycle to evaluate the occurrence, course, and profile of hematotoxicity. Further, we assessed the impact of hemoglobin levels and transfusion on oncological outcomes. Results : In a high-risk cervical cancer population with 82.3% of women with FIGO ≥ III stage, the 1-, 2-, and 5-year rates of overall survival (OS) were 89.1%, 74.7%, and 63.3%, and local control (LC) rates were 90.1%, 86.1%, and 75.0%, respectively. Grade 3 leukopenia was present in 2.1% and grade 3 anemia in 4.3%. No higher grade ≥ 4 hematotoxicity was observed. Absolute hemoglobin levels significantly reduced after the fourth cycle, with a median time from the start of therapy to hemoglobin nadir of 36 days. A lower hemoglobin nadir (<9 g/dL) was significantly associated with inferior LC. Red blood cell transfusion was applied in 44.9% of the women; the necessity of transfusion was significantly correlated to inferior OS, LC, and distant control. Conclusions : Our results suggest the need for special consideration of increased hematotoxicity and consistent implementation of anemia therapy, particularly from the fourth RT week onwards, to enable full-course definitive radiochemotherapy for locally advanced cervical cancer patients.

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED 10 ) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED 10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT.

Our study aims to identify the risk factors and dosimetry characteristics associated with capsular contracture., Methods: We retrospectively analyzed 118 women with breast cancer who underwent PMRT following an IBR between 2010 and 2022. Patients were treated with PMRT of 50.0-50.4 Gy in 25-28 fractions. Capsular contracture was categorized according to the Baker Classification for Reconstructed Breasts., Results: After a median follow-up of 22 months, the incidence of clinically relevant capsular contracture (Baker III-IV) was 22.9%. Overall, capsular contracture (Baker I-IV) occurred in 56 patients (47.5%) after a median of 9 months after PMRT. The rate of reconstruction failure/implant loss was 25.4%. In the univariate analysis, postoperative complications (prolonged pain, prolonged wound healing, seroma and swelling) and regional nodal involvement were associated with higher rates of capsular contracture ( p = 0.017, OR: 2.5, 95% CI: 1.2-5.3 and p = 0.031, respectively). None of the analyzed dosimetric factors or the implant position were associated with a higher risk for capsular contracture., Conclusion: Postoperative complications and regional nodal involvement were associated with an increased risk of capsular contracture following breast reconstruction and PMRT, while none of the analyzed dosimetric factors were linked to a higher incidence. Additional studies are needed to identify further potential risk factors.

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rank p = 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging.

(1) Background: To assess dosimetry benefits of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of liver metastases. (2) Methods: This is a subgroup analysis of an ongoing prospective registry including patients with liver metastases. Patients were treated at the MRIdian Linac between February 2020 and April 2022. The baseline plan was recalculated based on the updated anatomy of the day to generate the predicted plan. This predicted plan could then be re-optimized to create an adapted plan. (3) Results: Twenty-three patients received 30 SMART treatment series of in total 36 liver metastases. Most common primary tumors were colorectal- and pancreatic carcinoma (26.1% respectively). Most frequent fractionation scheme (46.6%) was 50 Gy in five fractions. The adapted plan was significantly superior compared to the predicted plan in regard to planning-target-volume (PTV) coverage, PTV overdosing, and organs-at-risk (OAR) dose constraints violations (91.5 vs. 38.0%, 6 vs. 19% and 0.6 vs. 10.0%; each p < 0.001). Plan adaptation significantly increased median BEDD95 by 3.2 Gy (p < 0.001). Mean total duration of SMART was 72.4 min. (4) Conclusions: SMART offers individualized ablative irradiation of liver metastases tailored to the daily anatomy with significant superior tumor coverage and improved sparing of OAR.

The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients' and physicians' ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients' and physicians' assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients' self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians' or patients' assessment was seen, while a moderate and substantial agreement was detected between the physicians' and the patients' assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.

Background: Proton beam radiotherapy (PBT) offers physical dose advantages that might reduce the risk for secondary malignancies (SM). The aim of the current study is to calculate the risk for SM after X-ray-based 3D conformal (3DCRT) radiotherapy, intensity-modulated radiotherapy (IMRT), and active pencil beam scanned proton therapy (PBS) in patients treated for thymic malignancies., Methods: Comparative treatment plans for each of the different treatment modalities were generated for 17 patients. The risk for radiation-induced SM was estimated using two distinct prediction models-the Dasu and the Schneider model., Results: The total and fatal SM risks estimated using the Dasu model demonstrated significant reductions with the use of PBS relative to both 3DCRT and IMRT for all independent thoracic organs analyzed with the exception of the thyroid gland ( p ≤ 0.001). SM rates per 10,000 patients per year per Gy evaluated using the Schneider model also resulted in significant reductions with the use of PBS relative to 3DCRT and IMRT for the lungs, breasts, and esophagus ( p ≤ 0.001)., Conclusions: PBS achieved superior sparing of relevant OARs compared to 3DCRT and IMRT, leading to a lower risk for radiation-induced SM. PBS should therefore be considered in patients diagnosed with thymic malignancies, particularly young female patients.

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates.

Background: To evaluate differences in local tumor control (LC), symptoms and quality of life (QOL) of 261 patients with VS after stereotactic radiosurgery/hypofractionated stereotactic radiotherapy (SRS/HFSRT) vs. fractionated radiotherapy (FRT) vs. fractionated proton therapy (FPT) were studied., Methods: For SRS/HFSRT ( n = 149), the median fraction dose applied was 12 Gy. For FRT ( n = 87) and FPT ( n = 25), the median cumulative doses applied were 57.6 Gy and 54 Gy (RBE), respectively. FRT and FPT used single median doses of 1.8 Gy/Gy (RBE). Median follow-up was 38 months. We investigated dosimetry for organs at risk and analyzed toxicity and QOL by sending out a questionnaire., Results: LC was 99.5% at 12 months after RT with no statistical difference between treatment groups ( p = 0.19). LC was significantly lower in NF2 patients ( p = 0.004) and in patients with higher tumor extension grade ( p = 0.039). The hearing preservation rate was 97% at 12 months after RT with no statistical difference between treatment groups (p = 0.31). Facial and trigeminal nerve affection after RT occurred as mild symptoms with highest toxicity rate in FPT patients., Conclusion: SRS/HFSRT, FRT and FPT for VS show similar overall clinical and functional outcomes. Cranial nerve impairment rates vary, potentially due to selection bias with larger VS in the FRT and FPT group.

Purpose: To assess the value of whole blood transcriptome data from liquid biopsy (lbx) in recurrent high-grade glioma (rHGG) patients for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR)., Methods: Whole blood transcriptome (WBT) analysis (Illumina HumanHT-12 Expression BeadChips) was performed in 14 patients with rHGG pre re-irradiation (reRT) with CIR and 3, 6 and 9 weeks post-CIR (reRT grade III:5, 36%, IV:9, 64%). Patients were irradiated with 30, 33, 36 GyRBE ( n = 5, 6, 3) in 3GyRBE per fraction., Results: WTB analysis showed stable correlation with treatment characteristics and patients tumor grade, indicating a preserved tumor origin specific as well as dynamic transcriptional fingerprints of peripheral blood cells. Initial histopathologic tumor grade was indirectly associated with TMEM173 (STING), DNA-repair (ATM, POLD4) and hypoxia related genes. DNA-repair, chromatin remodeling (LIG1, SMARCD1) and immune response (FLT3LG) pathways were affected post-CIR. Longitudinal WTB fingerprints identified two distinct trajectories of rHGG evolution, characterized by differential and prognostic CRISPLD2 expression pre-CIR., Conclusions: Lbx based WTB analysis holds the potential for molecular stratification of rHGG patients and therapy monitoring. We demonstrate the feasibility of the peripheral blood transcriptome as a sentinel organ for identification of patient, tumor characteristics and CIR specific fingerprints in rHGG.

Endometrial cancer is a common malignancy in elderly women that are more likely to suffer from limiting medical comorbidities. Given this narrower therapeutic ratio, we aimed to assess the oncologic outcomes and toxicity in the adjuvant setting. Out of a cohort of 975 women, seventy patients aged ≥ 80 years, treated with curative postoperative radiotherapy (RT) for endometrial cancer between 2005 and 2021, were identified. Outcomes were assessed using Kaplan-Meier-analysis and comorbidities using the Charlson Comorbidity Index and G8 geriatric score. The overall survival at 1-, 2- and 5-years was 94.4%, 82.6%, and 67.6%, respectively, with significant correlation to G8 score. At 1- and 5-years, the local control rates were 89.5% and 89.5% and distant control rates were 86.3% and 66.9%, respectively. Severe (≥grade 3) acute toxicity was rare with gastrointestinal (2.9%), genitourinary (1.4%), and vaginal disorders (1.4%). Univariate analysis significantly revealed inferior overall survival with lower RT dose, G8 score, hemoglobin levels and obesity, while higher grading, lymphangiosis, RT dose decrease and the omission of chemotherapy reduced distant control. Despite older age and additional comorbidities, elderly patients tolerated curative treatment well. The vast majority completed treatment as planned with very low rates of acute severe side-effects. RT offers durable local control; however, late distant failure remains an issue.

Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (-9.6%; p = 0.01) and visuospatial construction (-14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (-10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6-213.8 months) there was only one recurrence, in a patient's locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade > II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

Objective : Although local definitive radiotherapy (RT) is considered the standard of care for solitary plasmacytoma (SP), the optimal RT parameters for SP patients have not been defined. The aim of this retrospective study is to analyze the effectiveness of various RT doses, volumes, and techniques, as well as to define the relevant prognostic factors in SP. Methods : Between 2000 and 2019, 84 patients, including 54 with solitary bone plasmacytoma (SBP) and 30 with extramedullary plasmacytoma (EMP), underwent RT at six institutions. Results : The overall RT median dose was 42 Gy (range, 36.0-59.4). The median follow-up period was 46 months. Overall, the local control (LC) rate was 96%, while the complete remission (CR) rate was 46%. The 5-year local relapse-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS), and overall survival (OS) rates were 89%, 71%, 55%, and 93%, respectively. Using an RT dose above 40 Gy was associated with a higher complete remission (CR) rate and a lower rate of local relapse. Modern irradiation techniques were associated with a trend toward a higher LC rate (98% vs. 87% for conventional, p = 0.09) and a significantly lower local relapse rate (6% vs. 25% for conventional, p = 0.04). However, RT dose escalation and technique did not lead to a significant effect on MMFS, PFS, and OS. Univariate analyses identified several patient characteristics as potentially relevant prognostic factors. In SBP patients, systemic therapy administration was associated significantly with MMFS and PFS rates. Conclusion : Using an RT dose >40 Gy and modern RT techniques may improve the local control and reduce the rate of relapse, without a significant impact on survival rates. The addition of systemic therapies may improve the MMFS and PFS rates of SBP patients.