Real-time sonoelastography performed in addition to B-mode ultrasound and mammography: improved differentiation of breast lesions?

Hyperthermia is an important component of many cancer treatment protocols. In our study the regulation of the multidrug resistance (MDR) transporter P-glycoprotein by hyperthermia was studied in multicellular prostate tumor spheroids. Hyperthermia treatment of small (50-100 microm) tumor spheroids significantly increased P-glycoprotein and mdr-1 mRNA expression with a maximum effect at 42 degrees C, whereas only moderate elevation of P-glycoprotein was found in large (350-450 microm) tumor spheroids. Hyperthermia caused an elevation of intracellular reactive oxygen species (ROS). Inhibition of ROS generation with NADPH-oxidase inhibitors diphenylen iodonium (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF) abolished P-glycoprotein expression but did not affect its transcript levels following heat treatment. This indicates that P-glycoprotein levels are controlled by regulating its translation rate or stability. Hyperthermia incubation resulted in a differential activation of p38 mitogen-activated protein kinase (MAPK), extracellular regulated kinase 1,2 (ERK1,2), and c-jun N-terminal kinase (JNK) immediately, 4 hr and 24 hr after treatment. Furthermore, upregulation of hypoxia-inducible factor 1alpha (HIF-1alpha) was observed. Elevation of HIF-1alpha and P-glycoprotein expression following hyperthermia treatment were abolished upon coadministration of the p38 inhibitor SB203580. In contrast the JNK inhibitor SP600125 and the ERK1,2 inhibitor UO126 resulted in increase of HIF-1alpha and P-glycoprotein in the control as well as the hyperthermia-treated samples, indicating negative regulation of intrinsic HIF-1alpha and P-glycoprotein expression by ERK1,2 and JNK signaling cascades. In summary our data demonstrate that hyperthermia-induced upregulation of P-glycoprotein and HIF-1alpha is mediated by activation of p38, whereas ERK1,2 and JNK are involved in repression of P-glycoprotein and HIF-1alpha under control conditions.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.20596

Regulation of the multidrug resistance transporter P-glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Purpose: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. Methods: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n = 43) or the same treatment with additional deep regional hyperthermia (n = 60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). Results: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p = 0.09). Five-year rates for OS (88% versus 76%, p = 0.08), DFS (77% versus 73%, p = n.s.) and DMFS (75% versus 77%, p = n.s.) were not statistically different between the two groups. Conclusion: Radiochemotherapy combined with hyperthermia resu...

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer.

Purpose: The present study compares quality of life (QoL) after neoadjuvant radiochemotherapy with or without hyperthermia in patients with advanced rectal cancerMethods: Between April 1994 and May 1999, 137 patients were treated by neoadjuvant radiochemotherapy with (69 patients (504%)) or without (68 patients (496%)) hyperthermia Forty-six patients (336%) filled-out a ‘Gastrointestinal Quality of Life Index’ (GIQLI) questionnaire at four time points (before and after neoadjuvant therapy, early after surgery and after long-term follow-up) and were included in the present studyResults: There were no statistically significant differences in the global GIQLI index between patients treated with neoadjuvant radiochemotherapy with and without hyperthermia at any time point The longitudinal analysis of GIQLI values in both treatment groups showed specific profiles that were identical in both treatment groups Occurrence of severe toxicity during the neoadjuvant therapy in both arms lead to a significant 

Influence of neoadjuvant radiochemotherapy combined with hyperthermia on the quality of life in rectum cancer patients.

Objective: Topotecan and gemcitabine have shown mono-activity against different solid tumors including recurrent ovarian cancer after failure of platinum- and paclitaxel-containing

Dose finding study for combination treatment with topotecan and gemcitabine of patients with recurrent ovarian cancer after failure of first-line chemotherapy with paclitaxel and platinum

Background: The local recurrence rate of colorectal cancer has been significantly reduced due to the use of combined radiochemotherapy. Despite this improvement regarding locally ad

/pdf/feasibility-and-morbidity-of-combined-hyperthermia-and-2vmbfryepm.pdf

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer--preliminary results.

Background: Even today patients who suffer from mantle cell lymphoma have a poor prognosis, especially when the CNS is involved. To confirm the diagnosis of meningeosis lymphomatosa

/pdf/suboccipital-lateral-injection-of-intrathecal-chemotherapy-5czit1ipwc.pdf

Suboccipital Lateral Injection of Intrathecal Chemotherapy in a Patient with Mantle Cell Lymphoma

Abstract Purpose The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. Methods Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). Results For all three GTVs, the median DSC was 0.75 (range 0.17–0.95), the median HD 15 (range 3.22–67.11) mm, the median PBD 0.33 (range 0.06–4.86), and the median VS was 0.88 (range 0.31–1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. Conclusion Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA. 

/pdf/interobserver-agreement-on-definition-of-the-target-volume-2phknbmu.pdf

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

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Papers

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer--preliminary results.

Suboccipital Lateral Injection of Intrathecal Chemotherapy in a Patient with Mantle Cell Lymphoma

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.