Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Potential dosimetric benefit of an adaptive plan selection strategy for short-course radiotherapy in rectal cancer patients

An adaptive plan selection strategy can account for daily target volume variations for radiotherapy in rectal cancer patients. The aim was to quantify the daily dosimetric consequences of plan selection compared to a non-adaptive approach. Ten patients with rectal cancer, treated with 25Gy in five fractions to the mesorectum and pelvic lymph nodes, were selected. The adaptive strategy was simulated by creating three plans per patient, with varying upper ventral PTV margins, and selecting the smallest PTV covering the entire mesorectum on every daily CBCT scan. Subsequently, mesorectum, bladder, and bowel cavity were delineated on these scans. Daily dose-volume histograms were calculated for both the adaptive and non-adaptive plan, with a ventral PTV margin of 20mm. Coverage of the mesorectum, defined as V95%>99%, was calculated, as well as bladder and bowel cavity V95% and V15Gy. In one patient, mesorectum coverage improved. A reduction in bladder V95% and bowel cavity V15Gy was found, of 6.9% and 18.4cm(3) (p <0.01), respectively. Plan selection for radiotherapy in rectal cancer can improve coverage of the target volume. Overall dosimetric sparing of bladder and bowel cavity was limited but could be beneficial for individual patient

A systematic review of regional hyperthermia therapy in bladder cancer

ContextBladder cancer therapy remains suboptimal as morbidity and mortality remain high amongst those with non-muscle-invasive and muscle-invasive disease. Regional hyperthermia therapy (RHT) is a promising adjunctive therapy being tested in multiple clinical contexts.ObjectiveThe aim of this study was to systematically review the literature on the efficacy and toxicity of RHT.Evidence acquisitionThis systematic review was registered with the PROSPERO database (Registration number: CRD42015025780) and was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently and a third reviewer arbitrated disagreements. The last search was performed on 28 August 2015. A descriptive analysis was performed and quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Cochrane Risk of Bias Assessment Tool for trials.Evidence synthesisWe identified 859 publications in the initial search, of which 24 met inclusion criteria for full-text review. Of these, we were able to obtain data on the outcomes of interest for 15 publications.ConclusionsThe review underscores the limited nature of the evidence; definitive conclusions are elusive. However, the promising results of RHT in the setting of intravesical chemotherapy, chemotherapy and radiotherapy show a trend towards legitimate efficacy

Shared decision making: Prostate cancer patients' appraisal of treatment alternatives and oncologists' eliciting and responding behavior, an explorative study

Objective: To assess clinicians' use of shared decision making (SDM) skills, enabling patient treatment evaluations (appraisals); and varieties of patient appraisals and clinicians' preceding and following utterances. Methods: Two coders rated videotaped initial visits of 25 early-stage prostate cancer patients to their radiation oncologist. SDM skills were assessed using the Decision Analysis System for Oncology (DAS-O); appraisals and clinicians' utterances were labeled using qualitative methodology. Results: Clinicians offered a treatment choice to 10 patients. They informed 15/25 about pros and 20/25 about cons of options. Patients expressed 67 appraisals (median/visit = 2; range, 0-12). Half of appraisals were favorable and one-fourth was unfavorable toward treatment options. One-fifth referred to explicit tradeoffs. One-third of appraisals followed clinician requests; 58% followed clinician information. Clinicians approved almost half of appraisals. They contested, ignored or highlighted a minority. Conclusion: Clinicians infrequently offered patients a choice or explored appraisals. Most appraisals supported rather than challenged treatment options. Clinicians most often legitimized appraisals, thereby helping patients to feel good about the decision. Exploring appraisals may help patients in forming more stable preferences, thus benefiting patients in the long run. Practice implication: Clinicians should request patient appraisals and ascertain whether these seem well-informed before making treatment recommendations. (C) 2011 Elsevier Ireland Ltd. All rights reserve

Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots

Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to improve the heating quality. The aim of this study was to evaluate the clinical benefit of online treatment planning during treatment of pelvic tumors heated with the AMC-8 locoregional hyperthermia system. For online adaptive hyperthermia treatment planning, a graphical user interface was developed. Electric fields were calculated in a preprocessing step using our in-house-developed finite-difference-based treatment planning system. This allows instant calculation of the temperature distribution for user-selected phase-amplitude settings during treatment and projection onto the patient's computed tomographic scan for online visualization. Online treatment planning was used for 14 treatment sessions in 8 patients to reduce the patients' reports of hot spots while maintaining the same level of tumor heating. The predicted decrease in hot spot temperature should be at least 0.5°C, and the tumor temperature should decrease less than 0.2°C. These predictions were compared with clinical data: patient feedback about the hot spot and temperature measurements in the tumor region. In total, 17 hot spot reports occurred during the 14 sessions, and the alternative settings predicted the hot spot temperature to decrease by at least 0.5°C, which was confirmed by the disappearance of all 17 hot spot reports. At the same time, the average tumor temperature was predicted to change on average -0.01°C (range, -0.19°C to 0.34°C). The measured tumor temperature change was on average only -0.02°C (range, -0.26°C to 0.31°C). In only 2 cases the temperature decrease was slightly larger than 0.2°C, but at most it was 0.26°C. Online application of hyperthermia treatment planning is reliable and very useful to reduce hot spots without affecting tumor temperature

Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation

Background: The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. Methods: We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m(2) and carboplatin AUC2. Results: Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. Conclusion: In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limite

TREATMENT RESULTS OF PDR BRACHYTHERAPY COMBINED WITH EXTERNAL BEAM RADIOTHERAPY IN 106 PATIENTS WITH INTERMEDIATE- TO HIGH-RISK PROSTATE CANCER

Purpose: To evaluate treatment outcome of pulsed dose-rate brachytherapy (PDR) combined with external-beam radiotherapy (EBRT) for the treatment of prostate cancer. Methods and Materials: Between 2002 and 2007, 106 patients were treated by EBRT combined with PDR and followed prospectively. Two, 38, and 66 patients were classified as low-, intermediate-, and high-risk disease respectively according to the National Comprehensive Cancer Network criteria. EBRT dose was 46 Gy in 2.0-Gy fractions. PDR dose was increased stepwise from 24.96 to 28.80 Gy. Biochemical disease free survival and overall survival were determined by the Kaplan-Meier method. Cumulative incidence of late gastrointestinal (GI) and genitourinary (GU) toxicity were scored, according to the Common Terminology Criteria for Adverse Events. Results: The 3- and 5-year biochemical nonevidence of disease (bNED) were 92.8% (95% confidence interval [CI], 87.1-98.5) and 89.5% (95% CI, 85.2-93.8), respectively. Overall survival at 3 and 5 years was 99% (95% CI, 96-100) and 96% (95% CI, 90-100), respectively. The 3- and 5-year Grade 2 GI toxicity was 5.3% (95% CI, 0-10.6) and 12.0% (95% CI, 1.4-22.6), respectively. No Grade 3 or higher GI toxicity was observed. The 3- and 5-year Grade 2 or higher GU toxicity was 18.7% (95% CI, 10.3-27.1) and 26.9% (95% CI, 15.1-38.7), respectively. Conclusion: Results on tumor control and late toxicity of EBRT combined with PDR are good and comparable to results obtained with EBRT combined with high-dose-rate brachytherapy for the treatment of prostate cancer. (C) 2011 Elsevier In

Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study

Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer. Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0. The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%. Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperature

Clinical validation of a novel thermophysical bladder model designed to improve the accuracy of hyperthermia treatment planning in the pelvic region

Purpose: Hyperthermia treatment planning for deep locoregional hyperthermia treatment may assist in phase and amplitude steering to optimize the temperature distribution. This study aims to incorporate a physically correct description of bladder properties in treatment planning, notably the presence of convection and absence of perfusion within the bladder lumen, and to assess accuracy and clinical implications for non muscle invasive bladder cancer patients treated with locoregional hyperthermia. Methods: We implemented a convective thermophysical fluid model based on the Boussinesq approximation to the Navier–Stokes equations using the (finite element) OpenFOAM toolkit. A clinician delineated the bladder on CT scans obtained from 14 bladder cancer patients. We performed (1) conventional treatment planning with a perfused muscle-like solid bladder, (2) with bladder content properties without and (3) with flow dynamics. Finally, we compared temperature distributions predicted by the three models with temperature measurements obtained during treatment. Results: Much higher and more uniform bladder temperatures are predicted with physically accurate fluid modeling compared to previously employed muscle-like models. The differences reflect the homogenizing effect of convection, and the absence of perfusion. Median steady state temperatures simulated with the novel convective model (3) deviated on average −0.6 °C (−12%) from values measured during treatment, compared to −3.7 °C (−71%) and +1.5 °C (+29%) deviation for the muscle-like (1) and static (2) models, respectively. The Grashof number was 3.2 ± 1.5 × 105 (mean ± SD). Conclusions: Incorporating fluid modeling in hyperthermia treatment planning yields significantly improved predictions of the temperature distribution in the bladder lumen during hyperthermia treatment