Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non-invasively measure the 3D-temperature. This study investigates MRT accuracy for MR-hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland–Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R² (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland-Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi-institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi-institution studies of MR-guided hyperthermia and to elucidate thermal dose-effect relations.

Background: To prospectively analyze feasibility and pathological complete response (pCR) rates of neoadjuvant chemoradiotherapy combined with regional hyperthermia (RHT) in patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer. Methods: between 2012 and 2018, 111 patients with UICC stage IIB-IV or any locally recurrent rectal cancer were included (HyRec-Trial, ClinicalTrials.gov Identifier: NCT01716949). Patients received radiotherapy with concurrent 5-Fluororuracil (5-FU)/Capecitabine and Oxaliplatin, and RHT. Stage 1 feasibility analysis evaluated dose-limiting toxicities (DLT) after 19 patients, stage 2 after 59 evaluable patients. Analysis of the pCR rate was based on histopathological reports. Results: the feasibility rates for stages 1 and 2 were 90% (17/19) and 73% (43/59), respectively. In the intention-to-treat population the pCR rate was 19% (20/105; 90% confidence interval (CI) 13.0–26.5). In the per-protocol-analysis, complete tumor regression was seen in 28% (18/64) and 38% (3/8) of the patients with LARC and LRRC, respectively. Complete resection rates (R0) among patients with LARC and LRRC who received surgery were 99% (78/84) and 67% (8/12). Conclusions: the intensified neoadjuvant and multimodality treatment schedule was feasible and led to comparable early toxicity rates as described by other trials that used the similar chemoradiation protocol. The presented treatment regimen resulted in a very high pCR rate and appears as a promising option for patients with LRRC.

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.1% ≥ T3, 63.6% N1, 17.6%, M1) and 215 women (84.2% ≥ T3, 56.7% N1, 22.8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy. The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes. Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed. However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men. However, women also recover quickly and there are no long-term differences in quality of life.

Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition patterns and applicator efficiency (1–2%), the reduced heat transfer of the water boluses (51–56%) could be compensated by adjusting the water bolus flow. Skin surface temperatures were monitored reliably, and no alteration of thermal toxicity was observed compared to standard Amsterdam UMC thermometry. Conclusion: Clinical application of the TMS is feasible. Power deposition patterns and applicator efficiency were not affected. Surface temperatures were monitored reliably.

In recent years attention has focused on γH2AX as a very sensitive double strand break indicator. It has been suggested that γH2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by γH2AX in a large cohort. In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-γH2AX antibodies and microscopic images with an extended depth of field were acquired. γH2AX foci counting was performed using a semi-automatic image analysis software. Distinct increased values of preexisting and remaining γH2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR. The γH2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.

Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate differences in patients’ PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age.