Purpose Stereotactic radiosurgery (SRS) yields excellent local control in patients with a limited number of brain metastases (BMs), but radiation-induced cerebral edema and radiation necrosis (RN) in particular pose as a dose-limiting late toxicity, with the same holding true after fractionated radiotherapy for glioma. In symptomatic patients, the first-line standard of care includes corticosteroids, which may, however, be counterproductive in the evolving era of immunotherapy. Boswellic acid (BA), available as an over-the-counter dietary supplement, has been suggested as a potential corticosteroid-sparing alternative due to its anti-inflammatory and anti-angiogenic effects. Methods We performed a comprehensive literature search of the MEDLINE, Embase, Scopus, and Cochrane databases, identifying publications reporting on the use of BA during or after brain irradiation in humans. Using the RAMESES framework, relevant data are summarized using a meta-narrative approach. Results Six records (three for edema reduction in large irradiated volumes and three for RN after SRS) were identified, encompassing 130 patients. Roughly half of patients benefited from BA (radiographically or clinically) and about one-third could successfully taper dexamethasone or prevent its long-term intake. Tolerability of BA was favorable, with mild gastrointestinal discomfort being reported most frequently. Current drawbacks include unknown optimal formulation as well as timing and dosing, a considerably large number of required daily capsules, and uncertain interactions with other drugs. Conclusion Overall, the clinical evidence on the use of BA for radiation-induced cerebral edema and RN is lacking and well-designed prospective trials are warranted to further investigate this potential low-cost corticosteroid-sparing option.
We explored the dynamic changes of major leukocyte subsets during definitive treatment of patients with inoperable stage II/III NSCLC lung cancer and correlated it to survival to identify subpopulations associated with maximal patient benefit. We analyzed peripheral blood of 20 patients, either treated with thoracic radiotherapy (RT), concurrent chemo-radiotherapy (cCRT), or cCRT with additional immune-checkpoint inhibition therapy. Peripheral blood of 20 patients was collected at 9 timepoints before, during, and up to 1 year post treatment and analyzed by multi-color flow cytometry. Statistical analysis was conducted for leukocyte subpopulations, IL-6, progression-free survival (PFS) and overall survival (OS). Increase of absolute lymphocyte counts (ALC) after the end of RT until 6 months thereafter was a predictor of PFS. Baseline lymphocyte counts showed no significant correlation to PFS or OS. Early recovery of absolute counts (AC) at 3 weeks after RT, total CD3 + T-cells, and CD8 + cytotoxic T-cells distinguished those patients with favorable PFS (≥ 12 months) from all other patients. Discriminant analysis identified B-cells, neutrophil-lymphocyte-ratio (NLR), CD4 + T-helper-cells, and NK-cells as predictors of favorable PFS. High variability in IL-6 plasma concentration of consecutive measurements within 6 months after the end of RT correlated negatively with PFS. Our results suggest that two parameters commonly assessed in clinical routine can be used to predict patient outcome. These are: early increase in CD8 + T-cell lymphocyte count and variability in IL-6 plasma concentration, that are correlated to patients with favorable, respectively, poor outcome after definitive therapy independent of treatment regimen.
Introduction The recent advent of personalised assays capable of detecting circulating cell-free tumour DNA (ctDNA) has enabled detection of molecular residual disease (MRD) and recurrence following curative-intent therapy. We conducted LIONESS, a single-centre prospective cohort study to assess ctDNA in patients with HNSCC receiving primary surgery with curative intent to determine whether post-operative ctDNA detection can act as a biomarker for surgical tumour clearance and to evaluate the potential of personalised ctDNA analysis for early molecular-level detection of relapse or prior to clinically confirmed recurrence.
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.
Background:The impact of cranial radiotherapy (RT) on overall survival (OS) of patients with brain metastasis (BM) from non-small cell lung cancer (NSCLC) receiving programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors remains unclear. We aimed to examine the effect of previous cranial RT on the efficacy and neurological toxicity of PD-1/PD-L1 inhibitors in the treatment of patients with NSCLC.Methods:Patient-level data from seven prospective trials involving atezolizumab for the treatment of NSCLC [BIRCH (NCT02031458), FIR (NCT01846416), IMpower130 (NCT02367781), IMpower131 (NCT02367794), IMpower150 (NCT02366143), OAK (NCT02008227), and POPLAR (NCT01903993)] were pooled. Patients with baseline BM were divided into two subgroups based on previous cranial RT before initiation of treatment: patients with previously irradiated BM (iBM) and patients with non-irradiated BMs (niBM).Results:The per-protocol population consisted of 4,714 patients, including 3,176 in the atezolizumab group and 1,538 in the comparator chemotherapy group. In the atezolizumab group, OS was better in patients with BM (n=308) compared to patients without BM (n=2,868) [hazard ratio (HR): 0.83; 95% confidence interval (CI): 0.70-0.98; P=0.028]. Among patients with BM, patients with iBM (n=280) had a numerically longer OS (HR: 0.66; 95% CI: 0.41-1.07; P=0.090) than those with niBM (n=28). Intriguingly, OS was longer in patients with iBM than those without BM before (HR: 0.83; 95% CI: 0.70-0.99; P=0.043) and after (HR: 0.40; 95% CI: 0.32-0.49; P<0.0001) propensity score matching, while OS was similar between patients with niBM and those without BM. The survival advantage of patients with iBM over those without BM was not observed in the chemotherapy group. Atezolizumab-related serious neurological adverse events occurred in 16 (0.6%) patients without BM, none in those with niBM, and 2 (0.7%) patients with iBM.Conclusions:These data suggest potential synergistic effects of cranial RT and anti-PD-(L)1 therapy in NSCLC patients, which warrants further validation.
Abstract Background The prognosis of patients with anaplastic thyroid cancer (ATC) remains dismal. A small portion of patients experience longterm survival and need to be identified before treatment allocation. Survival scores may guide clinicians making more informed decisions about treatment options and improve the understanding of patients’ prognosis. The aim of this study was to validate two prognostic scores using an independent dataset to analyze which prognostic index is superior in discriminating survival. Methods Thirty-four patients with histologically confirmed ATC diagnosed between January 2009 and December 2019 were consecutively treated at our department and evaluated. Next generation sequencing was performed in 7 (21%) patients, but no druggable mutation was found. 50% of all patients received surgery and 56% were treated with chemoradiotherapy. The median radiation dose in equivalent dose in 2 Gy fractions (EQD2) was 50 Gy (SD:21 Gy). The study compared the discrimination of the Sugitani Prognostic Index (SPI) and the Marchand-Crety Prognostic Score (MCPS) using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 6-month survival. Results The median survival of the entire cohort was 5 months (range: 1-133). The AUC for 6-month survival was 0.85 (95% confidence interval [CI]:0.72–0.97) for SPI and 0.69 (95% CI: 0.56–0.83) for MCPS (p < 0.0001). Using the net reclassification index (NRI), 73% of patients were correctly reclassified using SPI instead of MCPS for 6-month survival (p = 0.0237). Conclusion The SPI was more accurate than the MCPS to determine patients’ life expectancies and should be recommended for clinical guidance and treatment allocation. In the last decade, comprehensive genetic profiling of actionable mutations in ATC has become vital to guide targeted therapy.
Training of interdisciplinary clinical reasoning and decision-making skills, essential in daily clinical practice in oncological specialties, are still underrepresented in medical education. Therefore, at LMU University Hospital Munich, we implemented a didactically modified tumor board simulation with experts from five different disciplines (medical oncology, pathology, radiation oncology, radiology, and surgery) presenting patient cases into a one-week course on the basic principles of oncology. In this survey, we examined the self-assessed impact of our course on the interdisciplinary decision-making skills of medical students. Between November-December 2023 and January-February 2024, we surveyed two cohorts of medical students in the third year of medical school in our one-week course before and after participating in the tumor board simulation. The objective was to evaluate the self-assessed knowledge in interdisciplinary clinical decision-making, in integrating ethical considerations into clinical reasoning, and in comprehension of various professional viewpoints in interdisciplinary decision-making. Knowledge was assessed using a five-step Likert scale from 1 (no knowledge) to 5 (complete knowledge). The survey was answered by 76 students before and 55 after the simulation, equaling 60–70
Durvalumab after chemotherapy in non-operable stage III non-small cell lung cancer (NSCLC) is the standard of care worldwide. We present a patient with the incidental discovery of a unilateral MALT lymphoma of the adrenal gland and adrenalitis during durvalumab maintenance treatment detected by 18F-FDG-PET/CT. We assessed the clinical and histopathological findings, radiological examinations and overall treatment. Our work emphasizes the significance of considering other differential diagnoses and the importance of multidisciplinary treatment of the findings, especially within clinical trials.
Hintergrund Abhängig von der Bestrahlungsdosis und -technik entwickeln bis zu 20% der Patienten ein bis sechs Monate nach thorakaler Strahlentherapie eine Grad-≥ 2-Pneumonitis, klinisch charakterisiert durch Husten, Dyspnoe, Fieber und/oder respiratorische Insuffizienz [1].In der Mehrheit der Fälle kann dies außerdem zu einer irreversiblen Fibrose führen, was mit hoher Morbidität und potenzieller Mortalität einhergehen kann.Obwohl das Risiko bei der definitiven Radiotherapie von primären oder sekundären Lungentumoren am höchsten ist, sind auch Patienten mit Ösophagus-, Mediastinal-oder sogar Brustbestrahlung (wenn z.B. die Lymphabflusswege mitbestrahlt werden) gefährdet.Präventive oder therapeutische Maßnahmen sind nach wie vor deutlich limitiert.Nach vielversprechenden Ergebnissen von Nintedanib bei verschiedenen Lungenerkrankungen (z.B. idiopathische Lungenfibrose) führten Rimner und Mitarbeiter eine prospektive, randomisierte Phase-II-Studie durch, um die therapeutische Effektivität dieses Tyrosinkinaseinhibitors (Anti-FGF-R1 und -3, Anti-PDGF-Ra und b,