Florian Putz

Clearance of primary necrotic cells by non-professional phagocytes

Homotypic internalisation of tumour cells has frequently been observed in tumour tissue sections. Events of non‐professional phagocytosis, however, may also occur in normal tissue if the number of dying cells exceeds the phagocytic capacity of professional phagocytes such as macrophages and dendritic cells. The aim of this study was to investigate the molecular background of non‐professional phagocytosis of primary necrotic cells by neighbouring tumour cells and normal skin fibroblasts.

A Model to Predict the Feasibility of Concurrent Chemoradiotherapy With Temozolomide in Glioblastoma Multiforme Patients Over Age 65.

Objectives: It is controversial whether concurrent chemoradiotherapy (CRT) with temozolomide is feasible and beneficial in elderly patients with glioblastoma. Materials and Methods: Retrospective analysis of 74 elderly glioblastoma patients (65 y and above) treated with concurrent CRT with temozolomide. Factors influencing prognosis and feasibility of CRT were investigated. Results: The median overall survival was 11.3 months. Univariate analysis showed a significant difference in median overall survival for cumulative dose of concurrent temozolomide (optimal cutoff, 2655 mg/m2; 13.9 mo for >2655 mg/m2 vs. 4.9 mo for ⩽2655 mg/m2; P=0.0216, adjusted for multiple testing). Furthermore, cumulative dose of concurrent temozolomide >2655 mg/m2 was a significant independent prognostic parameter in multivariate analysis (hazard ratio, 0.33; P=0.002). Hematotoxicity was the most common cause of treatment interruption or discontinuation in patients with an insufficient cumulative temozolomide dose. Prognostic factors for successful performance of CRT with a cumulative dose of concurrent temozolomide >2655 mg/m2 were female sex (odds ratio [OR], 0.174; P=0.006), age (OR, 0.826 per year; P=0.017), and pretreatment platelet count (OR, 1.013 per 1000 platelets/µL; P=0.001). For easy clinical application of the model an online calculator was developed, which is available at http://www.OldTMZ.com. Conclusions: The probability of successful performance of concurrent CRT with temozolomide can be estimated based on the patient’s age, sex, and pretreatment platelet count using the model developed in this study. Thus, a subgroup of elderly glioblastoma patients suitable for chemoradiation with temozolomide can be identified.

Regional deep hyperthermia: impact of observer variability in CT-based manual tissue segmentation on simulated temperature distribution

The aim of this study was to systematically investigate the influence of inter- and intra-observer segmentation variation of tumor and organs at risk on the simulated temperature coverage of the target. CT scans of six patients with tumors in the pelvic region acquired for radiotherapy treatment planning were used for the hyperthermia treatment planning. To study the effect of inter-observer variation, three observers manually segmented in the CT images of each patient the following structures: fat, muscle, bone and bladder. The gross tumor volumes (GTV) were contoured by three radiation oncology residents and used as hyperthermia target volume. For the intra-observer variation, one of the observers of each group contoured the structures of each patient three times with a time span of one week between the segmentations. Moreover, the impact of segmentation variations in organs at risk (OARs) between the three inter-observers was investigated on simulated temperature distributions using only one GTV. The spatial overlap between individual segmentations was assessed by the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Additionally, the temperatures T90/T10 delivered to 90%/10% of the GTV, respectively were assessed for each combination observer combination. The results of the segmentation similarity evaluation showed that the DSC of inter-observer variation of fat, muscle, bladder, bone and target was 0.68±0.12, 0.88±0.05, 0.73±0.14, 0.91±0.04 and 0.64±0.11, respectively. Similar results were found for the intra-observer variation. The MSD gave results like DSC for both observer variations. A statistically significant difference (p<0.05) was found for T90 and T10 in the predicted target temperature due to the observer variability. The conclusion is that intra- and inter-observer variations have a significant impact on the temperature coverage of the target. Furthermore, the organs at risk, such as bone and bladder, may essentially influence the homogeneity of the simulated target temperature distribution.The aim of this study was to systematically investigate the influence of the inter- and intra-observer segmentation variation of tumors and organs at risk on the simulated temperature coverage of the target. CT scans of six patients with tumors in the pelvic region acquired for radiotherapy treatment planning were used for hyperthermia treatment planning. To study the effect of inter-observer variation, three observers manually segmented in the CT images of each patient the following structures: fat, muscle, bone and the bladder. The gross tumor volumes (GTV) were contoured by three radiation oncology residents and used as the hyperthermia target volumes. For intra-observer variation, one of the observers of each group contoured the structures of each patient three times with a time span of one week between the segmentations. Moreover, the impact of segmentation variations in organs at risk (OARs) between the three inter-observers was investigated on simulated temperature distributions using only one GTV. The spatial overlap between individual segmentations was assessed by the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Additionally, the temperatures T90/T10 delivered to 90%/10% of the GTV, respectively, were assessed for each observer combination. The results of the segmentation similarity evaluation showed that the DSC of the inter-observer variation of fat, muscle, the bladder, bone and the target was 0.68  ±  0.12, 0.88  ±  0.05, 0.73  ±  0.14, 0.91  ±  0.04 and 0.64  ±  0.11, respectively. Similar results were found for the intra-observer variation. The MSD results were similar to the DSCs for both observer variations. A statistically significant difference (p  <  0.05) was found for T90 and T10 in the predicted target temperature due to the observer variability. The conclusion is that intra- and inter-observer variations have a significant impact on the temperature coverage of the target. Furthermore, OARs, such as bone and the bladder, may essentially influence the homogeneity of the simulated target temperature distribution.