Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Combined hyperthermia and radiotherapy for prostate cancer: a systematic review.

Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation oncologist. Dose escalation or combination of RT with systemic therapies is used to improve tumor control in patients with unfavorable prostate cancer, at the risk of increasing rates and severity of treatment-related toxicities. Elevation of temperature to a supra-physiological level has been shown to both increase tumor oxygenation and reduce DNA repair capabilities. Thus, hyperthermia (HT) combined with RT represents a compelling treatment strategy to improve the therapeutic ratio in prostate cancer patients. The aim of the present systematic review is to report on preclinical and clinical evidence supporting the combination of HT and RT for prostate cancer, discussing future applications and developments of this combined treatment.

Mild hyperthermia by MR-guided focused ultrasound in an ex vivo model of osteolytic bone tumour: optimization of the spatio-temporal control of the delivered temperature.

BACKGROUND: Magnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model for the induction of uniform temperature elevation in osteolytic bone tumours, using the natural acoustic window provided by the cortical breakthrough. MATERIALS AND METHODS: Experiments were conducted on ex vivo lamb shank by mimicking osteolytic bone tumours. The cortical breakthrough was exploited to induce hyperthermia inside the medullar cavity by delivering acoustic energy from a phased array HIFU transducer. MR thermometry data was acquired intra-operatory using the proton resonance frequency shift (PRFS) method. Active temperature control was achieved via a closed-loop predictive controller set at 6 °C above the baseline. Several beam geometries with respect to the cortical breakthrough were investigated. Numerical simulations were used to further explain the observed phenomena. Thermal safety of bone heating was assessed by cross-correlating MR thermometry data with the measurements from a fluoroptic temperature sensor inserted in the cortical bone. RESULTS: Numerical simulations and MR thermometry confirmed the feasibility of spatio-temporal uniform hyperthermia (± 0.5 °C) inside the medullar cavity using a fixed focal point sonication. This result was obtained by the combination of several factors: an optimal positioning of the focal spot in the plane of the cortical breakthrough, the direct absorption of the HIFU beam at the focal spot, the "acoustic oven effect" yielded by the beam interaction with the bone, and a predictive temperature controller. The fluoroptical sensor data revealed no heating risks for the bone and adjacent tissues and were in good agreement with the PRFS thermometry from measurable voxels adjacent to the periosteum. CONCLUSION: To our knowledge, this is the first study demonstrating the feasibility of MR-guided focused ultrasound hyperthermia inside the medullar cavity of bones affected by osteolytic tumours. Our results are considered a promising step for combining adjuvant mild hyperthermia to external beam radiation therapy for sustained pain relief in patients with symptomatic bone metastases.

Early closure of fistula using neo-adjuvant intra-arterial chemotherapy in locally advanced anal cancer.

BACKGROUND: Locally advanced anal cancer patients, especially with T4 disease and fistula, have a dismal prognosis. Neo-adjuvant intra-arterial chemotherapy before standard chemoradiation has been shown to be promising in this setting. AIMS: We are reporting results from a larger patient population. METHODS: From 2005 to 2015, 25 consecutive patients with locally advanced anal cancer, 18 of them fistulised, received intra-arterial chemotherapy. RESULTS: Twenty-two of 25 patients (88%) had T4N0-3 disease and 3 (12%) T3N3. An objective tumour response was observed in 24 of 25 patients (96%): 24 partial responses and 1 with stable disease. Fistulas' complete closure was observed in 15 of 18 patients (83.3%). Following intra-arterial chemotherapy, 23 patients underwent chemoradiation. Twenty-one of 25 patients (84%) had a complete remission 6 months after treatment completion. Amongst 22 patients followed for 3 or more years, 18 of them (81%) are colostomy free at 3 years. Five-year overall survival is 75%. Most frequent grade 3-4 toxicity of IAC was neutropenia (25%). CONCLUSIONS: Neo-adjuvant intra-arterial chemotherapy combined to chemoradiation resulted in a high rate of fistulas closure and long-term control of locally advanced anal cancer. This interesting approach in the treatment of fistulised anal cancer, needs a prospective study before being considered a new standard strategy.

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

BACKGROUND: Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. MATERIAL AND METHODS: From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48-82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. RESULTS: After a median follow-up of 31 months (range, 9-89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15-0.93). CONCLUSION: Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

Effect of statins and anticoagulants on prostate cancer aggressiveness.

PURPOSE: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. MATERIALS AND METHODS: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. RESULTS: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). CONCLUSION: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

Influence of abdominal adiposity, waist circumference, and body mass index on clinical and pathologic findings in patients treated with radiotherapy for localized prostate cancer.

BACKGROUND: Increased body mass index (BMI) has been associated with more aggressive prostate cancer (PC). The relation among abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), waist circumference (WC), and BMI was compared with clinical and pathologic findings in patients treated with radiotherapy for localized PC. METHODS: VAT, SAT, WC (all measured by planning abdominopelvic computed tomography scan) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity measures significantly predicted risk for secondary malignancies. RESULTS: Of 276 analyzed patients, 80 (29%) were obese (BMI ≥ 30 kg/m(2) ). Median BMI at baseline was 27.6 kg/m(2) (interquartile range [IQR], 25.1-30.5 kg/m(2) ). Increased SAT and VAT were associated with a higher National Comprehensive Cancer Network (NCCN) PC risk group (P = .0001 and .008, respectively). Greater SAT was associated with a higher Gleason score (GS) (P = .030). Younger age at diagnosis was significantly correlated with higher SAT and BMI, whereas increased prostate size was found in patients with higher BMI, WC, SAT, and VAT. At a median follow-up of 42.3 months (IQR, 32.3-59.9 months), 15 secondary malignancies were observed. On multivariate analysis, VAT was a significant predictor for secondary cancers (adjusted hazards ratio, 1.014; P = .0001). CONCLUSIONS: Measurements of greater abdominal adiposity were strongly associated with adverse pathologic features in patients with localized PC, including higher GS and NCCN PC risk groups. Moreover, VAT was found to be a strong risk factor for secondary malignancies.