Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

PURPOSE: Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. MATERIAL AND METHODS: Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. RESULTS: With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). CONCLUSIONS: Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68-prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

Biological responses of human solid tumor cells to X-ray irradiation within a 1.5-Tesla magnetic field generated by a magnetic resonance imaging-linear accelerator.

Devices that combine magnetic resonance imaging with linear accelerators (MRL) represent a novel tool for MR-guided radiotherapy. However, whether magnetic fields (MFs) generated by these devices affect the radiosensitivity of tumors is unknown. We investigated the influence of a 1.5-T MF on cell viability and radioresponse of human solid tumors. Human head/neck cancer and lung cancer cells were exposed to single or fractionated 6-MV X-ray radiation; effects of the MF on cell viability were determined by cell plating efficiency and on radioresponsiveness by clonogenic cell survival. Doses needed to reduce the fraction of surviving cells to 37% of the initial value (D0s) were calculated for multiple exposures to MF and radiation. Results were analyzed using Student's t-tests. Cell viability was no different after single or multiple exposures to MRL than after exposure to a conventional linear accelerator (Linac, without MR-generated MF) in 12 of 15 experiments (all P > 0.05). Single or multiple exposures to MF had no influence on cell radioresponse (all P > 0.05). Cells treated up to four times with an MRL or a Linac further showed no changes in D0s with MF versus without MF (all P > 0.05). In conclusion, MF within the MRL does not seem to affect in vitro tumor radioresponsiveness as compared with a conventional Linac. Bioelectromagnetics. 37:471-480, 2016. © 2016 Wiley Periodicals, Inc.

A systematic review: effectiveness of rectal emptying preparation in prostate cancer patients.

While the importance of a consistent rectal volume during radiation therapy planning and treatment for patients receiving radiation therapy to the prostate is recognized, there is no clear guidance as to the most effective method. This review examines the evidence for the efficacy of rectal preparations. Eighteen papers were found where the primary aim was to investigate a rectal emptying intervention and included 5 different strategies. These included evacuation techniques, dietary interventions, laxatives, and enemas and were either investigated alone or in combination. There is no robust evidence to recommend one rectal emptying strategy over another. Further investigation in adequately powered clinical trials is advised.

Pretreatment nomogram to predict the risk of acute urinary retention after I-125 prostate brachytherapy.

PURPOSE: Acute urinary retention (AUR) after iodine-125 (I-125) prostate brachytherapy negatively influences long-term quality of life and therefore should be prevented. We aimed to develop a nomogram to preoperatively predict the risk of AUR. METHODS: Using the preoperative data of 714 consecutive patients who underwent I-125 prostate brachytherapy between 2005 and 2008 at our department, we modeled the probability of AUR. Multivariate logistic regression analysis was used to assess the predictive ability of a set of pretreatment predictors and the additional value of a new risk factor (the extent of prostate protrusion into the bladder). The performance of the final model was assessed with calibration and discrimination measures. RESULTS: Of the 714 patients, 57 patients (8.0%) developed AUR after implantation. Multivariate analysis showed that the combination of prostate volume, IPSS score, neoadjuvant hormonal treatment and the extent of prostate protrusion contribute to the prediction of AUR. The discriminative value (receiver operator characteristic area, ROC) of the basic model (including prostate volume, International Prostate Symptom Score, and neoadjuvant hormonal treatment) to predict the development of AUR was 0.70. The addition of prostate protrusion significantly increased the discriminative power of the model (ROC 0.82). Calibration of this final model was good. The nomogram showed that among patients with a low sum score (<18 points), the risk of AUR was only 0%-5%. However, in patients with a high sum score (>35 points), the risk of AUR was more than 20%. CONCLUSION: This nomogram is a useful tool for physicians to predict the risk of AUR after I-125 prostate brachytherapy. The nomogram can aid in individualized treatment decision-making and patient counseling.

Predictors in the outcome of 125I brachytherapy as monotherapy for prostate cancer.

A number of different prostate cancer treatment modalities exist. Nomograms are used to assist clinicians and patients in choosing the most appropriate treatment. However, the predicted outcome for (125)I brachytherapy is much worse than what would be expected considering the actual survival rates. This underestimation may result in suboptimal treatment decisions. Therefore, better predictors for outcome after (125)I brachytherapy are necessary. The following factors, which may either influence outcome or predict outcome after brachytherapy, are discussed: tumor characteristics and risk stratification, patient age at treatment, obesity, adjuvant androgen-deprivation therapy, prostate-specific antigen bounce, implantation technique and dosimetry. For the prediction of outcome after (125)I brachytherapy, as long as the quality of the implant is optimal, only high-risk prostate cancer was found to have a negative impact on outcome.

Health-related quality of life in patients with locally advanced prostate cancer after 76 Gy intensity-modulated radiotherapy vs. 70 Gy conformal radiotherapy in a prospective and longitudinal study.

PURPOSE: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. METHODS AND MATERIALS: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of > or =10 points were considered clinically relevant. RESULTS: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. CONCLUSIONS: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

Towards patient specific thermal modelling of the prostate.

The application of thermal modelling for hyperthermia and thermal ablation is severely hampered by lack of information about perfusion and vasculature. However, recently, with the advent of sophisticated angiography and dynamic contrast enhanced (DCE) imaging techniques, it has become possible to image small vessels and blood perfusion bringing the ultimate goal of patient specific thermal modelling closer within reach. In this study dynamic contrast enhanced multi-slice CT imaging techniques are employed to investigate the feasibility of this concept for regional hyperthermia treatment of the prostate. The results are retrospectively compared with clinical thermometry data of a patient group from an earlier trial. Furthermore, the role of the prostate vasculature in the establishment of the prostate temperature distribution is studied. Quantitative 3D perfusion maps of the prostate were constructed for five patients using a distributed-parameter tracer kinetics model to analyse dynamic CT data. CT angiography was applied to construct a discrete vessel model of the pelvis. Additionally, a discrete vessel model of the prostate vasculature was constructed of a prostate taken from a human corpse. Three thermal modelling schemes with increasing inclusion of the patient specific physiological information were used to simulate the temperature distribution of the prostate during regional hyperthermia. Prostate perfusion was found to be heterogeneous and T3 prostate carcinomas are often characterized by a strongly elevated tumour perfusion (up to 70-80 ml 100 g(-1) min(-1)). This elevated tumour perfusion leads to 1-2 degrees C lower tumour temperatures than thermal simulations based on a homogeneous prostate perfusion. Furthermore, the comparison has shown that the simulations with the measured perfusion maps result in consistently lower prostate temperatures than clinically achieved. The simulations with the discrete vessel model indicate that significant pre-heating takes place in the prostate capsule vasculature which forms a possible explanation for the discrepancy. Pre-heating in the larger pelvic vessels is very moderate, approximately 0.1-0.3 degrees C. In conclusion, perfusion imaging provides important input for thermal modelling and can be used to obtain a lower limit on the prostate and tumour temperature in regional hyperthermia. However, it is not sufficient to calculate in detail the prostate temperature distribution in individual patients. The prostate vasculature plays such a crucial role that a patient specific discrete vessel model of the prostate vasculature is required.

Prostate perfusion in patients with locally advanced prostate carcinoma treated with different hyperthermia techniques.

PURPOSE: We determined prostate perfusion in 18 patients with locally advanced prostate carcinoma treated with a combination of external beam irradiation and regional (10) or interstitial (8) hyperthermia. MATERIALS AND METHODS: Perfusion values were calculated from temperature elevations due to constant applied power and from transient temperature measurements after a change in applied power. Student's t test was used for comparing perfusion values with time and in the 2 groups. RESULTS: At the start of regional hyperthermia treatment mean estimated perfusion plus or minus standard deviation was 10 +/- 8 ml./100 gm. per minute. At the end of treatment mean perfusion was increased to 14 +/- 2 ml./100 gm. per minute (p <0.01). Achieved thermal parameters were a mean temperature of at least 40.3C +/- 0.6C in 90% of the prostate, 40.9C +/- 0.6C in 50% and a mean maximum temperature of 41.6C +/- 0.6C. At the end of interstitial hyperthermia treatment estimated mean perfusion was 47 +/- 5 ml./100 gm. per minute, which was significantly different compared with the end of regional hyperthermia (p < 0(-7) ). Mean temperature was at least 39.4C +/- 0.9C in 90% of the prostate and 41.8C +/- 1.6C in 50%, while mean maximum temperature was 53.1C +/- 6.3C. Systemic temperature increased during regional hyperthermia up to 38.6C, whereas during interstitial hyperthermia body temperature was not elevated. CONCLUSIONS: During interstitial hyperthermia perfusion values are higher than during regional hyperthermia. Hyperthermia causes increased prostate perfusion.

Three-dimensional controlled interstitial hyperthermia combined with radiotherapy for locally advanced prostate carcinoma--a feasibility study.

PURPOSE: To perform a feasibility study of three-dimensional spatially controlled interstitial hyperthermia for locally advanced prostate cancer. METHODS AND MATERIALS: Twelve patients with prostate cancer (T3NxM0) were treated with conventional external beam radiotherapy and one interstitial hyperthermia treatment. Hyperthermia was delivered with the 27-MHz multielectrode current source (MECS) interstitial hyperthermia technique on an outpatient basis. Guided by transrectal ultrasonography, 12 catheters (range 7-16) were placed in the prostate through a template. Two electrodes per probe were inserted. Thermometry (average 100 sensors) was performed from within the probes for online temperature control. Additional thermometry was done in the prostate, rectum, urethra, and bladder. Reconstruction was done by sonography. Prostate perfusion was estimated from the thermal decay at the end of treatment. The full three-dimensional temperature distribution was calculated. RESULTS: No toxicities greater than Grade 2 were recorded. A learning curve for implantation, position verification, reconstruction, and temperature simulation was experienced. Perfusion was 47 mL/100 g/min (range 30-65). The average measured temperature was T(90) (90% of the prostate reached a temperature of at least:) 39.9 degrees C and T(50) 44.1 degrees C. The average calculated temperatures were lower: T(90), 39.4 degrees C and T(50), 41.8 degrees C, because the entire prostate was taken into account. The tumor temperatures were T(90), 40.7 degrees C and T(50), 43.0 degrees C. The bladder and rectal temperatures were below the safety limits. CONCLUSION: Multielectrode-current-source interstitial hyperthermia is technically feasible and well tolerated. It was not possible to achieve the goal temperature of 42-43 degrees C because of high perfusion and implantation limitations.