Purpose: So far there is little evidence on peripherally inserted central venous catheter (PICC) in radiation oncology patients maintaining the access during the periods of ambulatory and hospital treatment. Methods: A total of 522 PICC placements in 484 patients were performed between 11/2011 and 07/2016 at the Department of Radiation Oncology and analysed retrospectively for complications and treatment- and patient-related factors during ambulatory and hospital inpatient use. On initial hospitalization, all patients received a multimodal radio-oncological treatment consisting of radiation and intravenous therapy administered via the PICC. Results: A total of 18,292 catheter days were documented. Median follow-up from catheter insertion to their removal was 37 days (1–97). The overall complication rate was 4.1 per 1000 catheter days (n = 75, 14.4%). Complications were similar between the cohort of outpatient 3.6 per 1000 catheter days and the cohort of inpatient 4.8 per 1000 catheter days (OR 0.976; 95% CI [0.598; 1.619]; p = 0.924). Severe bloodstream infections occurred at a rate of 0.60 per 1000 catheter days (n = 11, 2.1%), deep vein thrombosis at a rate of 0.82 per 1.000 catheter days (n = 15, 2.9%) and local inflammation at a rate of 1.26 per 1.000 catheter days (n = 23, 4.4%). Only immunotherapy could be identified as an independent risk factor for complications (OR 5.6; 95% CI [2.4; 13.1]; p < 0.001). Conclusion: Using PICC in outpatients is not associated with an elevated risk of complications. Particular attention should be payed to early identification of PICC associated bloodstream infections. Immunotherapy is an independent risk factor for local skin complication.

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: ¹⁰B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of ¹⁰B in the tumor but also on the organs at risk. It is not yet possible to determine the ¹⁰B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the ¹⁰B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of ¹⁰B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the ¹⁰B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.

This study determined with focus on gender disparity whether incidence based on age, tumor characteristics, patterns of care, and survival have changed in a population-based sample of 8288 German patients with head neck cancer (HNC) registered between 1996 and 2016 in Thuringia, a federal state in Germany. The average incidence was 26.13 ± 2.89 for men and 6.23 ± 1.11 per 100,000 population per year for women. The incidence peak for men was reached with 60–64 years (63.61 ± 9.37). Highest incidence in females was reached at ≥85 years (13.93 ± 5.87). Multimodal concepts increased over time (RR = 1.33, CI = 1.26 to 1.40). Median follow-up time was 29.10 months. Overall survival (OS) rate at 5 years was 48.5%. The multivariable analysis showed that male gender (Hazard ratio [HR] = 1.44; CI = 1.32 to 1.58), tumor subsite (worst hypopharyngeal cancer: HR = 1.32; CI = 1.19 to 1.47), and tumor stage (stage IV: HR = 3.40; CI = 3.01 to 3.85) but not the year of diagnosis (HR = 1.00; CI = 0.99 to 1.01) were independent risk factors for worse OS. Gender has an influence on incidence per age group and tumor subsite, and on treatment decision, especially in advanced stage and elderly HNC patients.

Boron neutron capture therapy (BNCT) is a binary cancer treatment modality where two different agents (¹⁰B and thermal neutrons) have to be present to produce an effect. A dedicated trial design is necessary for early clinical trials. The concentration of ¹⁰B in tissues is an accepted surrogate to predict BNCT effects on tissues. Tissue, blood, and urines were sampled after infusion of two different boron carriers, namely BSH and BPA in the frame of the European Organisation for Research and Treatment of Cancer (EORTC) trial 11001. In this study, urine samples were used to identify protein profiles prior and after drug infusion during surgery. Here, an approach that is based on the mass spectrometry (MS)-based proteomic analysis of urine samples from head and neck squamous cell carcinoma (HNSCC) and thyroid cancer patients is presented. This method allowed the identification of several inflammation- and cancer-related proteins, which could serve as tumor biomarkers. In addition, changes in the urinary proteome during and after therapeutic interventions were detected. In particular, a reduction of three proteins that were involved in inflammation has been observed: Galectin-3 Binding Protein, CD44, and osteopontin. The present work represents a proof of principle to follow proteasome changes during complex treatments based on urine samples.

The PI3K/Akt/mTOR pathway is frequently altered in human papillomavirus (HPV)-positive and negative squamous cell carcinoma of the head and neck (HNSCC) and overstimulation is associated with poor prognosis. PI3K drives Akt activation and constitutive signaling acts pro-proliferative, supports cell survival, DNA repair, and contributes to radioresistance. Since the small molecule NVP-BEZ235 (BEZ235) is a potent dual inhibitor of this pathway, we were interested whether BEZ235 could be an efficient radiosensitizer. The 50 nM BEZ235 was found to abrogate endogenous and irradiation-induced phosphorylation of Akt (Ser473). The anti-proliferative capacity of the drug resulted in an increase in G1-phase cells. Repair of radiation-induced DNA double-strand breaks (DSBs) was strongly suppressed. Reduction in DSB repair was only apparent in G1- but not in G2-phase cells, suggesting that BEZ235 primarily affects non-homologous end joining. This finding was confirmed using a DSB repair reporter gene assay and could be attributed to an impaired phosphorylation of DNA-PKcs (S2056). Cellular radiosensitivity increased strongly after BEZ235 addition in all HNSCC cell lines used, especially when irradiated in the G0 or G1 phase. Our data indicate that targeting the PI3K/Akt/mTOR pathway by BEZ235 with concurrent radiotherapy may be considered an effective strategy for the treatment of HNSCC, regardless of the HPV and Akt status.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody–drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.