Radiation Treatment For Prostate Cancer Research Articles

Exploring the Impact of Prostate Cancer Radiation Treatment on Functions, Bother, and Well-Being.

Though many studies have explored the effects of radiation therapy on urinary, sexual, and bowel function and/or bother, few have focused on symptom experiences from diagnosis through the first year following completion of radiation therapy. The purpose of this study was to compare the effect of 3 types of radiation treatment on functions, bother, and well-being in men with prostate cancer at 1, 6, and 12 months after completion of treatment. A repeated measures survey (N = 73) found that none of the function, bother, emotional, social, or functional well-being scores were significantly different among the 3 groups. However, within-subjects-only repeated measures ANCOVA suggested that emotional well-being and social well-being are different over time. The findings show that clinical treatment of prostate cancer has an impact on functions, bother, and well-being of patients. Thus, it is important that nurses and other healthcare providers listen to what patients are saying before, during, and after treatment.

Positron Emission Tomography (PET) Imaging of Prostate Cancer with a Gastrin Releasing Peptide Receptor Antagonist - from Mice to Men

Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy.Methods: Biodistribution, dosimetry and tumor uptake of the GRPr antagonist 64Cu-CB-TE2A-AR06 [(64Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG4-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH2] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7).Results: No adverse events were observed after injection of 64Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time.Conclusion: 64Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating 64Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

Risk Of Acute and Chronic Leukemias Following Radiation Treatment For Locoregional Prostate Cancer In The United States Over 35-Years

▪ BackgroundProstate cancer is the most common cancer diagnosis in men, and one of the leading indications for radiation therapy. The risk of resultant secondary leukemias has not been consistently established. We investigated the risk of all leukemias in a population-based cohort of patients (pts) with locoregional prostate cancer definitively treated with radiotherapy. MethodsWe queried the Surveillance, Epidemiology, and End Results (SEER) 17 registries to identify a cohort of men >20 years old (n = 183,268) with locoregional prostate adenocarcinoma newly diagnosed between January 1973 and December 2008. Pts who underwent initial treatment with radical prostatectomy (RP) were compared to pts receiving RP with external beam radiotherapy (RP w/EBRT) to investigate the risk of radiation-induced leukemias. These cohorts tend to be well matched regarding age, medical comorbidities and disease characteristics. All new leukemias occurring as a second primary cancer at least one year after the first diagnosis of prostate cancer were identified in SEER using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) morphology codes. Secondary leukemias included acute myeloid leukemia (AML); chronic myelogenous leukemia (CML); acute and chronic lymphocytic leukemia (ALL & CLL) and other categories as reported in SEER. Pts were observed from date of prostate cancer diagnosis until leukemia occurrence, death, or last date of follow-up. Univariate and multivariate analyses were performed using the Fine and Gray competing risk regression analysis with leukemia as a time-dependent endpoint and death from any cause or the diagnosis of any other second cancer as competing events. RP w/ EBRT group was compared with the RP cohort as the reference group, controlling for age. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. ResultsMedian age was 67 years (yrs, range 22 – 105) at prostate cancer diagnosis: 67 yrs in RP and 68 yrs in RP w/ EBRT pts (p<0.0001); 158,913 (86.7%) were treated with RP and 24,355 (13.3%) with RP w/EBRT. Median follow-up was 7.6 yrs [(range, 1 – 35.5): 7.5 yrs in the RP group and 8.3 yrs in the RP w/ EBRT group, (p<0.0001)].In total, 949 (0.5%) leukemia cases were identified: 336 (0.2%) acute leukemias [266 (0.2%) in the RP group and 70 (0.3%) in the RP w/ EBRT]; 538 (0.3%) chronic leukemias [462 (0.3%) in the RP group and 76 (0.3%) in the RP w/ EBRT] and 75 (0.04%) of unspecified histology. Histologic subtypes (per ICD-O-3 codes) were: AML (n=249), acute monocytic leukemia (n=18), ALL (n=24), other acute leukemias (n=45), other myeloid/monocytic/lymphocytic leukemias (n=48), aleukemic/subleukemic/NOS (n=27), CML (n=131) and CLL (n=407).Median age at acute leukemia diagnosis was 77 yrs [(range, 50 – 101): 78 yrs in the RP group and 76 yrs in RP w/EBRT pts, (p=0.0271)] and for chronic leukemias was 76 yrs [(range, 47 – 101): 76 yrs in the RP group and 77 yrs in the RP w/EBRT pts, (p=0.50)].The median time to develop acute leukemias was 6.0 yrs [(range, 1 – 28.2): 6.1 yrs in the RP group and 5.7 yrs in the RP w/EBRT pts, (p=0.20)] and chronic leukemias was 6.9 yrs [(range, 1 – 29.8): 6.7 yrs in the RP group and 8.6 yrs in the RP w/EBRT pts, (p=0.0020)]. The cumulative incidence rate (CIR) at 20 years for acute leukemias was 0.24% for the RP pts vs. 0.32% for the RP w/EBRT pts (p=0.0196). The CIR at 20 years for chronic leukemias was 0.47% for the RP pts vs. 0.36% for the RP w/EBRT pts (p=0.10).In univariate analyses, age >70 yrs (HR=1.40; CI, 1.13 – 1.74; p=0.0023), and those who received RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0033) were significantly more likely to develop acute leukemias. In multivariate analysis, both advanced age (HR=1.40; CI, 1.13 – 1.74; p = 0.0023) and RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0032), remained significantly associated with increased risk of acute leukemias. Radiation treatment was not significantly associated with the risk of developing chronic leukemias among pts treated with RP w/EBRT vs. RP [HR=0.91; CI, 0.72 – 1.16; p=0.45). ConclusionsAmong the best matched prostate cancer treatment cohorts, those who underwent EBRT following RP had a 49% increased risk of subsequent acute leukemias, although the absolute number of cases was low. Risk assessment in this cohort spans a time frame where radiation technologies have rapidly advanced and hence treatment period effects need to be considered in interpretation of results Disclosures:No relevant conflicts of interest to declare.

Optimizing CT Acquisition for Prostate Cancer Radiation Treatment Planning and Delivery

Optimizing CT Acquisition for Prostate Cancer Radiation Treatment Planning and Delivery

Feasibility of PET-CT 18F-fluorocholine to increase doses in intraprostatic lesions in radiation treatments for prostate cancer

Feasibility of PET-CT 18F-fluorocholine to increase doses in intraprostatic lesions in radiation treatments for prostate cancer

SU‐C‐WAB‐01: Computerized Production of Statistical Clinical Target Volume Models in Prostate Cancer Radiation Treatment Planning

Purpose: Inter‐and intra‐observer variability of clinical target volume (CTV) contours for prostate cancer is a critical issue in radiation treatment planning. Automated contouring based on statistical CTV models could be one of possible approaches for reducing the variability. Therefore, the purpose of our study is to develop a computerized method for producing the statistical CTV models to be used as CTV templates for automated contouring in prostate cancer radiation treatment planning. Methods: Eighteen, seventeen and sixteen radiation oncologists belonging to different facilities delineated CTV contours for low‐, intermediate‐and high‐risk prostate cancers, respectively. The low‐risk, intermediate‐risk, and high‐risk CTVs include only a prostate, a prostate plus a 1‐cm seminal vesicle base, and a prostate plus 2‐cm seminal vesicle, respectively. The statistical CTV models for the three risk types were derived based on a principal component analysis (PCA), which statistically took into account the inter‐observer variability. CTV regions were triangulated by using a marching cubes method. For matching the number of points on the surfaces of all CTV regions, the number of vertices on each CTV region was reduced to 1,000 with a quadric error metrics. All CTV regions were registered with a reference CTV by using an iterative closest point algorithm for calculation of a covariance matrix to be employed for the PCA‐based CTV modeling. Results: CTV models of three risk types were produced, which consisted of a mean CTV and PCA coefficients multiplied by eigenvectors, i.e., eigen‐CTV image. Average Euclidean distances between corresponding points of a mean CTV and the other CTVs for three risk types were 2.05 mm, 3.64 mm, 2.55 mm, respectively. Conclusion: The proposed method could provide probabilistic CTV models to be used as CTV templates in delineating CTV contours.

Wait times in prostate cancer diagnosis and radiation treatment

Introduction: Wait times for cancer diagnosis and treatment area significant concern for Canadians. Men with prostate cancerexperience longer waiting times for diagnosis and treatment thanthose observed for other cancers. Longer waits are associated withboth patient and family psychosocial distress and may be associatedwith worse prognosis.Methods: Men referred for treatment of prostate cancer at a singleCanadian cancer centre were interviewed. The intervals from suspicionto definitive therapy were calculated, factors associated withdelays along this pathway were identified, and common causes ofdelay identified by patients were described.Results: A total of 41 consecutive patients participated. The medianinterval from suspicion to the first fraction of radiotherapy forall patients was 247 days (interquartile range [IQR] 168-367 d).The median diagnostic interval was 53 days (IQR 28-166 d). Themedian treatment interval was 127 days (IQR 100-180 d). Patientsunder 70 years old and patients with &lt;T2c disease had shorterintervals from suspicion to treatment. From diagnosis to start ofradiotherapy, patients with low-risk disease had longer intervals.Seventy percent of patients perceived a delay in their care, ofwhich 45%, 31% and 24% of patients felt the delays were due tothe health care system, patient or physician factors, respectively.Interpretation: In this study, 12% and 0% of patients met CanadianStrategy for Cancer Control and Canadian Association of RadiationOncologists wait time recommendations, respectively. A large componentof wait time is patient driven. Alternate strategies shouldbe developed and measured to shorten the intervals between thesuspicion and treatment of prostate cancer.Introduction : Les temps d’attente pour recevoir un diagnosticde cancer et un traitement constituent une source importante depréoccupation pour les Canadiens. Les hommes atteints de cancerde la prostate attendent encore plus longtemps que les patientsatteints d’autres types de cancer pour obtenir un diagnostic etentreprendre un traitement. Ces attentes plus longues se traduisentpour le patient et sa famille par un stress psychosocial et peuventêtre liés à un pronostic plus sombre.Méthodologie : Des hommes aiguillés vers le même centre decancérologie au Canada pour la prise en charge d’un cancer dela prostate ont été interviewés. L’intervalle entre le soupçon decancer et le début réel du traitement a été calculé; on a cernéles facteurs liés aux retards le long du processus, et les causes deretards signalées par les patients ont été décrites.Résultats : Au total, 41 patients consécutifs ont participé. La duréemédiane de l’intervalle entre le soupçon de cancer et la premièreséance de radiothérapie pour tous les patients était de 247 jours(écart interquartile [EIQ], 168 à 367 jours). La durée médianede l’intervalle avant le diagnostic était de 53 jours (EIQ, 28 à166 jours). La durée médiane de l’intervalle avant le début dutraitement était de 127 jours (EIQ, 100 à 180 jours). Les patients deplus de 70 ans et les patients porteurs d’une tumeur T2c ou moinsavancée signalaient des intervalles plus courts entre les premierssoupçons de cancer et le traitement. Entre le diagnostic et le débutde la radiothérapie, les patients présentant une maladie à faiblerisque avaient des intervalles plus longs. Soixante-dix pour centdes patients ont perçu un retard dans leur prise en charge, parmilesquels 45 % croyaient ce retard lié au système de santé, 31 %, àdes facteurs liés au patient, et 24 %, à des facteurs liés au médecin.Interprétation : Dans cette étude, 12 % et 0 % des patients,respectivement, ont présenté des temps d’attentes conformes auxrecommandations de la Stratégie canadienne de lutte contre lecancer et de l’Association canadienne de radio-oncologie. Letemps d’attente est déterminé en grande partie par des facteurs liésau patient. D’autres stratégies devraient être élaborées et évaluéesafin de réduire les intervalles entre les premiers soupçons de cancerde la prostate et le début du traitement.

Role of choline PET/CT in guiding target volume delineation for irradiation of prostate cancer

Choline PET/CT has shown limitations for the detection of primary prostate cancer and nodal metastatic disease, mainly due to limited sensitivity and specificity. Conversely in the restaging of prostate cancer recurrence, choline PET/CT is a promising imaging modality for the detection of local regional and nodal recurrence with an impact on therapy management. This review highlights current literature on choline PET/CT for radiation treatment planning in primary and recurrent prostate cancer. Due to limited sensitivity and specificity in differentiating between benign and malignant prostatic tissues in primary prostate cancer, there is little enthusiasm for target volume delineation based on choline PET/CT. Irradiation planning for the treatment of single lymph node metastases on the basis of choline PET/CT is controversial due to its limited lesion-based sensitivity in primary nodal staging. In high-risk prostate cancer, choline PET/CT might diagnose lymph node metastases, which potentially can be included in the conventional irradiation field. Prior to radiation treatment of recurrent prostate cancer, choline PET/CT may prove useful for patient stratification by excluding distant disease which would require systemic therapy. In patients with local recurrence, choline PET/CT can be used to delineate local sites of recurrence within the prostatic resection bed allowing a boost to PET-positive sites. In patients with lymph node metastases outside the prostatic fossa and regional metastatic lymph nodes, choline PET/CT might influence radiation treatment planning by enabling extension of the target volume to lymphatic drainage sites with or without a boost to PET-positive lymph nodes. Further clinical randomized trials are required to assess treatment outcomes following choline-based biological radiation treatment planning in comparison with conventional radiation treatment planning.

Mining Surveillance Data: Does Radiation Treatment of Prostate Cancer Cause Rectal Cancer?

Prostate cancer (PC) is the most common invasive cancer among males, with most cases organ-confined at diagnosis. External beam radiation (RAD) and prostatectomy (SURG) represent the most common treatments for organ-confined PC, with RAD exposing the rectum to high-dose ionizing radiation. Using the California population for 1988-2009, we identified men treated with RAD and SURG for organ-confined PC and assessed the hazards ratio for rectal cancer five or more years following PC treatment. The adjusted Cox proportional hazards ratio was 39% higher for rectal cancer in the RAD cohort. Further analyses seek to distinguish roles of RAD dose and delivery.

Canadian Prostate Brachytherapy in 2012

Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.

A mechanistic description of radiation-induced damage to normal tissue and its healing kinetics

We introduce a novel mechanistic model of the yield of tissue damage at the end of radiation treatment and of the subsequent healing kinetics. We find explicit expressions for the total number of functional proliferating cells as well as doomed (functional but non-proliferating) cells as a function of time post treatment. This leads to the possibility of estimating—for any given cohort of patients undergoing radiation therapy—the probability distribution of those kinetic parameters (e.g. proliferation rates) that determine times to injury onset and ensuing resolution. The model is suitable for tissues with simple duplication organization, meaning that functionally competent cells are also responsible for tissue renewal or regeneration following injury. An extension of the model to arbitrary temporal patterns of dose rate is presented. To illustrate the practical utility of the model, as well as its limitations, we apply it to data on the time course of urethral toxicity following fractionated radiation treatment and brachytherapy for prostate cancer.

Calculation of Dose in Healthy Organs, during Radiotherapy 4-Field Box 3D Conformal for Prostate Cancer, Simulation of the Linac 2300, Radiotherapy Room and MAX Phantom

In men, prostate cancer is one of the most frequent types, and radiotherapy is adopted as a form of treatment. Although there are efforts to minimize the dose in the healthy organ and tissues adjacent to the tumor during radiotherapy, these organs are affected by the secondary scattered and leakage radiation originating from the therapeutic beam and these doses deposited in the healthy organs, can induce the appearance of new focal points of cancer. The aim of this study is to calculate the equivalent and effective doses, due to photons and neutrons, in healthy organs of a patient submitted to radiotherapy treatment for prostate cancer. Computed simulation of radiotherapy treatment for prostate cancer was used to perform the dose calculations, adopting the treatment protocol used at INCA (Brazilian National Cancer Institute). The MCNPX code was employed in the simulation radiation transport while the male voxel MAX phantom was used to represent the patient's human anatomy. The results obtained in this study indicate that the organs close to the irradiated region are predominantly affected by the dose due to photons, with an impact on organs from different systems of the body, such as the bladder, colon, and testicles, besides bone structures such as the femur, pelvis and spinal column. The results obtained from the doses deposited due to neutrons suggest that tibia and fibula, mandible, cranium, brain and thyroid, had the highest dose deposited due to neutrons in relation to photons. The result obtained from the effective dose was 31.47 mSv due to photons, while the dose due to neutrons was 0.42 mSv. Note that the effective dose due to photons is significantly higher than the effective dose due to neutrons. The values calculated in this study were compared with the experimental values obtained in the literature, presenting reasonable concordance. Additionally, as described in the literature, it was verified that the dose due to photons decreases considerably with the increase in the distance of the target organ, while the dose due to neutrons is distributed homogeneously in the organs. It is concluded that the contribution of neutrons to the appearance of secondary cancers is more relevant in the organs furthest from the target volume, and that organs close to the tumor, are affected predominantly by the dose due to photons.

A randomised, double‐blind, placebo‐controlled trial of nightly sildenafil citrate to preserve erectile function after radiation treatment for prostate cancer

Erectile dysfunction (ED) is a common adverse event associated with treatment for prostate cancer. This study aimed to identify whether early, regular use of sildenafil after radiation treatment for prostate cancer is effective at reducing the rate of ED at 2 years. A randomised controlled trial with 27 men planned for radiation treatment for localised prostate cancer recruited from a single radiotherapy centre in Australia. Men were randomised to receive daily sildenafil, or a placebo tablet, for 6 months. The primary end-point was erectile function, as measured by the International Index of Erectile Function (IIEF) score, at 2-year follow-up. The abridged IIEF-5 survey was also used during the treatment period, and could be derived from the full IIEF at other time-points. Two-sided Student's t-tests and Mann-Whitney U-tests were used for the analysis of continuous outcomes, with Fisher's exact test for dichotomous outcomes. No difference was seen at 2 years in the primary end-point, and IIEF scores did not differ significantly between groups during the study. Men in the sildenafil group exhibited significantly better IIEF-5 scores at 4 weeks (P = 0.02) and 6 months (P = 0.02). There was no difference in erectile function scores between the two groups throughout the treatment period. No significant difference in adverse events was identified between the two groups. There was no evidence from this trial that sildenafil provides long-term erectile function for patients while on medication. Regular use of sildenafil may improve short-term sexual function for patients while on medication. Larger trials are required to examine the effectiveness of implementing sildenafil for prostate cancer patients undergoing radiation treatment.

Evaluation and Management of Rectourethral Fistula Following Radiation Treatment for Prostate Cancer

Rectourethral Fistula (RUF) is an unusual entity with severe consequences to patients. Radiation induced RUF is an infrequent complication following prostate cancer treatment. Evaluation and management of radiation induced RUF is not uniform. A variety of alternatives are offered to manage RUF, including but not limited to the transanal, transrectal approach (York-Mason), pure perineal and combined abdomino-perineal approaches. It is of utmost importance that the genitourinary reconstructive surgeon be familiar with the etiology, anatomy and options to treat RUF. Treatment strategies must be tailored with consideration toward the etiology of the fistula and to the patient status.

A Retrospective Planning Analysis Comparing Volumetric-Modulated Arc Therapy (VMAT) to Intensity-Modulated Radiation Therapy (IMRT) for Radiotherapy Treatment of Prostate Cancer

PurposeThis study aims to compare intensity-modulated radiation therapy (IMRT) to volumetric-modulated arc therapy (VMAT) for the treatment of prostate cancer. Particular focus was placed on the impact IMRT and VMAT have on departmental planning and treatment resources. Materials and MethodsTwenty prostate cancer cases were retrospectively planned to compare 5-field IMRT to VMAT using a single arc (VMAT-1A) and 2 arcs (VMAT-2A). The impact on departmental resources was assessed by comparing the time needed to generate the dose distributions and to deliver the treatment plan. A comparison of plan quality was also performed by comparing homogeneity, conformity, the number of monitor units (MUs), and dose to the organs at risk. ResultsIMRT and VMAT-2A were able to produce adequate plans for all cases. Using VMAT-1A, planning guidelines were achieved in 8 of the 20 cases. IMRT provided an improved dose distribution and the best homogeneity to the planning target volume. Also, the IMRT plans were generated significantly faster than both VMAT techniques. VMAT planning provided significantly improved conformity and used significantly fewer monitor units than IMRT. VMAT-1A treatments were significantly faster than both IMRT and VMAT-2A. VMAT plans delivered lower dose to the bladder and heads of femur, and an increased dose to the rectum in the low dose region. ConclusionIMRT may have an advantage over VMAT for the treatment of prostate cancers. This is primarily due to the uncertainty of achieving planning guidelines using VMAT and the extended time needed to generate the VMAT plans.

PS1-18: Development and Characterization of a Cohort for Determining Long Term Secondary Side Effects Due to Radiation Treatment for Prostate Cancer Using an Electronic Health Record

Background/Aims The long term secondary side effects from radiation treatment for prostate cancer are well described. Here we characterize a cohort with radiation treatment for prostate cancer and an electronic medical record. A subset of individuals, were selected for EPIC quality of life surveys.

Cost-effectiveness of Intensity-modulated Radiotherapy in Prostate Cancer

AimsTo compare the costs and effectiveness of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3DCRT) for the radical treatment of localised prostate cancer at elevated doses (>70 Gy). Materials and methodsA cost-effectiveness analysis model was developed using clinical effectiveness estimates from a systematic review. The base case analysis assumes equal biochemical survival for IMRT and 3DCRT, but lower frequency of gastrointestinal toxicity for IMRT. The costs of IMRT and 3DCRT were estimated through activity-based costing, incorporating input from radiation oncologists, physicists and treatment planners. ResultsThe delivery of IMRT produced 0.023 more quality-adjusted life-years (QALY) than 3DCRT at an additional cost of $621 (QALY and costs discounted at 5% per year), yielding an incremental cost-effectiveness ratio of $26 768 per QALY gained. The treatment cost of IMRT was $1019 more than 3DCRT, but IMRT resulted in less frequent gastrointestinal toxicity, thus avoiding $402 in the treatment of toxicity. In the scenario that compared a higher dose of IMRT (75.6 Gy) to 3DCRT (68.4 Gy), IMRT improved disease control with equal toxicity incidence, and the IMRT strategy dominated (less costly and more effective). In the base case scenario (no survival difference), the cost-effectiveness of IMRT was most sensitive to the treatment cost difference between IMRT and 3DCRT. ConclusionFor radical radiation treatment (>70 Gy) of prostate cancer, IMRT seems to be cost-effective when compared with an equivalent dose of 3DCRT.

TU-C-BRB-05: BEST IN PHYSICS (THERAPY) - Combined Effects of Pulsed Non-Thermal Focused Ultrasound and Radiotherapy for Prostate Cancer Treatment

Purpose: Recent studies have shown non-thermal effects of pulsed focused ultrasound (pFUS) on tumor growth control. This study is to investigate the combined effects of non-thermal pFUS and radiotherapy (RT) for prostate cancer treatment. Methods: Animal prostate tumor model was developed by implanting LNCaP cells in mice prostates. Tumor-bearing mice were randomly assigned to 3 groups (n=8): (1) pFUS; (2) pFUS+RT; (3) control. MR-guided pFUS treatment was performed using InSightec ExAblate 2000 system with a 1.5T GE MR scanner. Non-thermal sonications were delivered by keeping the body temperature <42°C as measured real-time by MR thermometry. Prostate tumors in groups 1 and 2 were exposed to pFUS (1MHz, 25W focused ultrasound; 1Hz pulse rate with a 10% duty cycle) for 60 sec for each sonication. Each tumor was covered entirely using 4–8 sonication spots. Prostate tumors in group 2 also received 2 Gy radiation dose within 30 minutes after pFUS treatment using Siemens Artiste (6MV photon energy, 300MU/min dose rate). Following the treatment, mice were scanned weekly using MRI for tumor volume measurement. Results: Tumor volumes in the control group showed exponential increase from 121±5 mm3 on treatment day to 172±9, 247±15, 344±28, and 500±42 mm3 at 1, 2, 3, and 4 weeks post treatment, respectively. In contrast, tumor volumes in the pFUS group were 33% (p<0.05), 29% (p<0.05), 14%, and 15% smaller, and the pFUS+RT group were 31%, 31%, 26%, 33% smaller (p<0.05) at week 1, 2, 3, and 4 post treatment, respectively. Both pFUS and pFUS+RT groups showed significant tumor growth delay in the first two weeks. Conclusions: Our study showed that pFUS combined with radiotherapy can significantly delay the tumor growth. Radiation after pFUS treatment provided an additional benefit for tumor control (sponsored by Focused Ultrasound Surgery Foundation, Varian Medical Systems, DOD PC073127, DOD BC102806).

Urethral strictures following high-dose-rate brachytherapy for prostate cancer: Analysis of risk factors

High-dose-rate brachytherapy is an established technique to deliver a conformal dose of radiation to patients with prostate cancer. The William Buckland Radiotherapy Center has been performing high-dose-rate brachytherapy with external beam radiation treatment for prostate cancer since 1998 and has an extensive prospective database on all patients treated. The purpose of this analysis was to assess the risk of stricture formation and identify the predictive or causative factors. Three hundred fifty-four patients were treated between 1998 and 2008. Patients received one of three differing dose schedules: 20Gy in four treatments (20Gy/4), 18Gy/3, and 19Gy/2 during three sequential time periods. Nelson-Aalen cumulative hazard modeling was used to estimate risk of events over time. Potential risk factors, including dose, were identified and used in the analysis. There were 45 patients who developed at least one stricture, an overall risk of 8.2% at 2 years. The 2-year risk of stricture formation was 3.4%, 2.3%, and 31.6% for 18Gy/3, 20Gy/4, and 19Gy/2, respectively. Most strictures occurred in the bulbomembranous urethra (50%) or external sphincter region (33%). On multivariable analysis, the dose schedule used was the only significant predictor for increased stricture formation. In our patients, those who received 19Gy/2 were at a significantly higher risk of stricture formation. Most of these strictures were mild, requiring only one intervention but a 2-year stricture risk of 31.6% was striking, and we have modified our protocol.

Abstract 1449: Spicing up radiation treatment for prostate cancer

Abstract Introduction and Objective: Radio-sensitizing agents sensitize cells to the lethal effects of ionizing radiation (IR). This permits use of lower doses of radiation to achieve equivalent cancer control thereby minimizing adverse effects to normal tissues. Given their lack of toxicity compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. Capsaicin is the active compound chilli peppers. Traditionally capsaicin is used to treat chronic pain syndromes; however, recently evidence using in vitro prostate cancer (PCa) models describes its anti-carcinogenic potential. In our preliminary studies we have demonstrated the radio-sensitizing capacity of in PCa cells in vitro. Cells treated with capsaicin and/or IR to have increased expression of pro-apoptotic tumour-suppressor proteins p21 and p27 and reduced androgen-receptor. The objective of the present study is to assess the radio-sensitizing capacity in an in vivo model. Methods: Athymic nude mice were inoculated subcutaneously with human PCa (LNCaP) cells. Once xenografts reach 100mm3 forty animals will be randomized into 4 groups (15 /group); control (no treatment), capsaicin alone, ionizing radiation (IR) alone and capsaicin and IR. Treatments were administered over a two-week time period. Capsaicin (5 mg/kg/d) or vehicle was administered 3/week by gavage. RT will be delivered to animals in sterile cages as one fraction (6 Gray). Control animals were mock irradiated. Tumours were measured thrice weekly and volumes were calculated. Tumours were fixed and stained for pathological analyses and immunohistochemical evaluation. Results: There were no differences in food consumption or body weight of mice between groups. Two mice experienced mild to moderate inflammation of the stomach. No other toxicities were observed. Mice treated with capsaicin or IR alone had a significant reduction in tumour growth overtime (p &amp;lt; 0.001). Mice treated with capsaicin and IR capsaicin had a reduction in the tumour volume greater than either capsaicin alone (p&amp;lt;0.001) or radiation alone.(p&amp;lt;0.03) We are currently investigating mechanism. Conclusion: These studies confirm the radio-sensitizing capacity of capsaicin in PCa xenograft model cells. Ongoing studies using are further delineating the mechanism of interaction of these treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1449. doi:1538-7445.AM2012-1449