Olga Knaus

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.

The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment.