Markus Anton Schirmer

Background/Objectives: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive tumor, primarily affecting elderly patients. Radiotherapy (RT) remains an important treatment option, particularly for patients who are ineligible for systemic chemotherapy. This study aims to identify prognostic factors and evaluate recurrence patterns in a real-world cohort of PCNSL patients treated with RT. Methods: We retrospectively analyzed 64 PCNSL patients treated with radiotherapy at our institution between 2000 and 2022. Clinical characteristics, treatment details, and outcomes were collected by chart review. Overall survival (OS) was analyzed using Kaplan–Meier and Cox regression methods. Recurrence patterns were assessed based on available post-treatment imaging. Results: Median patient age was 71 years (range: 31–83); 53.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Radiotherapy was used as first-line treatment in 62.5% of cases, primarily due to contraindications to chemotherapy. Median OS was 10 months from diagnosis. Age, poor performance status, seizures at presentation, absence of systemic therapy, incomplete radiotherapy, and <80% applied dose of planned radiotherapy were associated with inferior OS in our univariable analysis. Multivariable analysis confirmed age, systemic therapy, seizures, and radiotherapy dose <80% as independent predictors. Among twenty-nine patients with imaging follow-up, eight recurrences after RT were documented: six of those within, and two outside of the initially affected areas. All recurrences occurred within previously irradiated areas. Conclusions: This study confirms known negative prognostic factors in PCNSL and underscores the importance of systemic chemotherapy for curatively intended treatments aiming for prolonged survival. The recurrence patterns observed question the added benefit of whole-brain irradiation in preventing distant relapses. These findings support the need for prospective trials to optimize radiotherapy strategies while balancing efficacy and neurotoxicity.

Background: Combining external beam radiotherapy (EBRT) with high-dose-rate (HDR) brachytherapy (BT) enables biologically effective dose escalation in prostate cancer. However, comparative evaluation of such regimens using radiobiological modeling remains limited. Methods: Dose regimens based on clinical practice were analyzed using α/β values of 1.5 and 3 Gy for the prostate. Ten patients with available planning CT, pelvic MRI, and ultrasound-guided BT plans were retrospectively evaluated. Physical and biological dose distributions were recalculated for various EBRT and HDR-BT combinations. Biological effective dose (BED) values were determined for the prostate and organs at risk (OARs: anterior rectal wall, bladder base, urethra). Regimens yielding the highest ΔBED between prostate and OARs were considered most favorable. Results: All regimens met clinical dose constraints. The most favorable ΔBED profiles for bladder and rectum were observed with HDR-BT regimens (2 × 15 Gy) combined with either 23 × 2 Gy or 15 × 2.5 Gy EBRT, independent of the assumed α/β value. EBRT-only regimens achieved superior urethral sparing, while higher HDR doses led to increased urethral exposure. Conclusions: This study underscores the value of radiobiological modeling in differentiating and optimizing prostate cancer radiotherapy strategies. While the trade-offs between dose escalation and OAR sparing are clinically known, our biologically driven analysis provides a more quantitative foundation for selecting and tailoring combined EBRT/HDR-BT regimens in practice.

Brain metastases and leptomeningeal carcinomatosis (LC) are complications of advanced-stage malignancies, associated with a poor prognosis. This study aimed to evaluate the role of prognostic factors and radiotherapy (RT) treatment approaches while taking toxicity into account. We performed a retrospective study and compared clinical characteristics, prognostic factors, toxicities and outcomes in patients with (1) parenchymal brain metastases (PM) (n = 275) vs. LC (n = 35) and (2) in patients with whole brain radiotherapy (WBRT) (n = 52) vs. WBRT + boost (n = 201). We found poorer survival (OS) of the LC group compared to PM patients in univariable analysis (not in multivariable analysis). LC patients predominantly underwent WBRT only, received surgical resection before RT less frequently and had more RT discontinuations than PM patients. OS was better in the WBRT + boost group than in the WBRT only group. In patients who received WBRT + boost, the primary tumor was more often controlled, and the number of PM was lower compared to the WBRT only group. WBRT + boost was associated with higher rates of alopecia than WBRT only. Patients with LC had a worse prognosis compared to patients with PM. WBRT + boost resulted in higher toxicity than WBRT only but resulted in better OS in the presented study. WBRT + boost patients had more favorable prognostic factors prior to RT, so OS improvement is not likely due to boost. Treating brain metastases requires a careful assessment of benefits and risks. Optimal RT planning should consider prognostic factors and potential side effects individually.

Purpose: In definitive radiotherapy/radiochemotherapy (RT/RCT) for localized non-small cell lung cancer (NSCLC), the introduction of positron-emission tomography (PET)-CT-based staging/RT planning and dynamic RT techniques (intensity-modulated radiotherapy, IMRT/volumetric modulated arc therapy, VMAT) were important innovations. Methods: We performed a retrospective study and compared clinical outcomes (1) in patients with PET-CT-based staging ( n = 170) vs. conventional staging ( n = 103) and (2) in patients with dynamic RT techniques (IMRT/VMAT; n = 99) vs. three-dimensional conformal radiotherapy (3D-CRT; n = 64). Results: We found improved survival with PET-CT vs. conventional staging. PET-CT patients vs. conventionally staged patients had higher applied RT doses, higher RT completion rates, and a higher rate of patients who received RCT vs. RT only. Additionally, we found higher rates of leukopenia and lung infections in PET-CT patients. When comparing RT techniques (IMRT/VMAT vs. 3D-CRT), there were no differences in survival. IMRT/VMAT patients had higher RT doses and higher rates of intensified concomitant chemotherapy (cisplatin/vinorelbine vs. low-dose cisplatin). IMRT/VMAT was associated with a reduction in pneumonitis and dermatitis. Conclusion: In summary, refined RT/RCT strategies with PET-CT and IMRT/VMAT enable the intensification of multimodal treatment. Reduction of toxicities with IMRT/VMAT widens the therapeutic window. The coincidence of intensified treatment, improved outcomes, and higher toxicity rates in PET-CT-staged patients emphasizes the need for a detailed risk–benefit assessment during planning and application of treatment modalities.

In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012–2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified.

Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery followed by postoperative radiochemotherapy (RCT). With the general increase in life expectancy, the proportion of elderly patients with HNSCC is expected to grow rapidly. Until now, a deeper understanding of specific management strategies for these patients in clinical routine was lacking. In the present study, we compared elderly patients (≥70 years, n = 52) and younger patients (n = 245) treated with postoperative RCT for HNSCC at our tertiary cancer center. All patients were irradiated with modern radiotherapy techniques (IMRT/VMAT). Patients ≥70 years of age had more comorbidities. Additionally, elderly patients less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative RCT is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor overall survival rates, benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully. When exclusively applying up-to-date radiotherapy techniques with, at the same time, careful use of concomitant systemic therapy, favorable acute toxicity profiles are achieved.

Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer.

Background: Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our institution. Patients and Methods: We included patients who received curative CRT for anal cancer. We compared VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. Results: A total of 149 patients (3DCRT: n = 87, VMAT: n = 62) were included. The median follow-up was longer in 3DCRT-treated patients (3DCRT: 61.3 months; VMAT: 39.1 months; p < 0.05). VMAT-treated patients had more G3 tumors (3DCRT: 12/87 (13.8%); VMAT: 18/62 (29.0%), p < 0.001). VMAT reduced acute toxicities ≥grade 3 (3DCRT: n = 48/87 (55.2%); VMAT: n = 11/62 (17.7%), p < 0.001). VMAT improved treatment compliance (less interruptions/delays) (3DCRT: 37/87, 42.5%; VMAT: 4/62, 6.5%; p < 0.001), provided a shorter median overall treatment time (3DCRT: 41 days; VMAT: 38 days; p = 0.02), and gave a higher median absolute 5-fluorouracil dose (3DCRT: 13,700 mg; VMAT: 14,400 mg; p = 0.001). Finally, we found improved CSS (p = 0.02; 3DCRT: 81.9% at 3 years; VMAT: 94.1% at 3 years) and DC (p = 0.01; 3DCRT: 89.4% at 3 years; VMAT: 100.0% at 3 years) with VMAT. Summary: Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer. Previous studies have indicated that organs at risk sparing might be more improved with the use of VMAT vs. with conventional IMRT. Future studies should address whether these advantages lead to a further reduction in CRT-associated morbidity.