Monotherapy For Prostate Cancer Research Articles

Predictive Factors for Urinary Retention after Hdr Brachytherapy as Monotherapy for Prostate Cancer

Predictive Factors for Urinary Retention after Hdr Brachytherapy as Monotherapy for Prostate Cancer

Health-related quality of life changes due to high-dose rate brachytherapy, low-dose rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.

72 Background: To compare urinary, bowel, and sexual health-related quality of life (HRQOL) changes due to high-dose rate (HDR) brachytherapy, low-dose rate (LDR) brachytherapy, or intensity modulated radiation therapy (IMRT) monotherapy for prostate cancer. Methods: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2,700-2,800 cGy in two fractions (n=85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n=249), or IMRT monotherapy to 7,400-8,100 cGy in 37-45 fractions (n=79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an International Prostate Symptoms Score questionnaire, an Expanded Prostate cancer Index Composite-26 bowel questionnaire, and a Sexual Health Inventory for Men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pre-treatment and at 1, 3, 6, 9, 12, and 18 months post-treatment. Results: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months post-irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months following treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients following treatment. Conclusions: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.

Prediction model for early biochemical recurrence after radical prostatectomy based on the Cancer of the Prostate Risk Assessment score and the presence of secondary circulating prostate cells.

To establish a prediction model for early biochemical recurrence based on the Cancer of the Prostate Risk Assessment (CAPRA) score and the presence of secondary circulating prostate cells (CPCs). We conducted a prospective single-centre study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinicopathological findings were used to calculate the CAPRA score. At 90 days after surgery, blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs were identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen (PSA) but not CD45. The CPC test results were defined as positive or negative. Patients were followed up for up to 5 years and biochemical recurrence was defined as a PSA level >0.2 ng/mL. The validity of the CAPRA score was calibrated using partial validation, and Cox proportional hazard regression to build three models: a CAPRA score model, a CPC model and a CAPRA/CPC combined model. A total of 321 men, with a mean age of 65.5 years, participated in the study. After 5 years of follow-up the biochemical recurrence-free survival rate was 98.55%. For the model that included CAPRA score there was a hazard ratio (HR) of 7.66, for the CPC model there was an HR of 34.52 and for the combined model there were HRs of 2.60 for CAPRA score and 22.5 for CPC. Using the combined model, 23% of men changed from the low-risk to the high-risk category, or vice versa. The incorporation of CPC detection significantly improved the model's discriminative ability in establishing the probability of biochemical recurrence; patients in the high-risk group according to CAPRA score who are negative for CPCs have a much better prognosis. The addition of CPC detection gives clinically significant information to aid the decision on who may be eligible for adjuvant therapy.

Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer

Background and purposeThe use of HDR brachytherapy (HDR-BT) as monotherapy for prostate cancer (PC) is increasing worldwide with good tumour control rates and acceptable toxicity. We report our results on toxicity and quality of life (QoL) after HDR-BT monotherapy for PC patients. Materials and methods166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38Gy in four fractions. Genitourinary (GU) and gastrointestinal (GI) toxicities were prospectively assessed using EORTC-RTOG questionnaires and physicians charts. QoL was evaluated using EORTC QLQ-PR25 questionnaires. ResultsThree months after treatment, acute GU and GI toxicities were reported in 10.8% and 7.2%. Acute toxicity resolved within two months in the majority of patients (61%). Late grade ⩾2 GU and GI toxicity were reported in 19.7% and 3.3% of patients 12months after HDR-BT. Mean QLQ-PR25 scores showed clinically relevant changes from baseline for urinary symptoms and sexual functioning. With a mean follow-up of 35months, biochemical failure was observed in 2.4%. Overall survival at 60months was 93.6% and cancer-specific survival was 100%. ConclusionsHDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity. Urinary symptoms and sexual function QoL decreased after treatment.

Repurposing Drugs in Oncology (ReDO)-nitroglycerin as an anti-cancer agent.

Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardiac oxygenation via multiple mechanisms including improved blood flow (vasodilation), decreased platelet aggregation, increased erythrocyte O2 release and decreased mitochondrial utilization of oxygen. Its vasoactive properties mean that it has the potential to exploit more fully the enhanced permeability and retention effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce HIF-1α levels in hypoxic tumour tissues and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG are summarised and discussed. While there is evidence of a positive action as a monotherapy in prostate cancer, there are mixed results in NSCLC where initially positive results have yet to be fully replicated. Based on the evidence presented, a case is made that further exploration of the clinical benefits that may accrue to cancer patients is warranted. Additionally, it is proposed that NTG may synergise with a number of other drugs, including other repurposed drugs, and these are discussed in the supplementary material appended to this paper.

Prostate cancer: High-dose-rate brachytherapy as monotherapy in prostate cancer.

Prostate cancer: High-dose-rate brachytherapy as monotherapy in prostate cancer.

Dose-volume analysis and the temporal nature of toxicity with stereotactic body radiation therapy for prostate cancer

PurposeThe purpose of this study was to evaluate the dose-volume relationships of genitourinary toxicity after stereotactic body radiation therapy (SBRT) monotherapy for prostate cancer. Methods and materialsFifty-six patients diagnosed with low- to intermediate-risk prostate cancer treated with SBRT alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. Overall, acute, and late genitourinary toxicity were documented according to the Common Terminology Criteria for Adverse Events (version 4) and International Prostate Symptom Scores (IPSS). ResultsThe median age at treatment was 68 years, and the median prostate volume was 45.5 mL, with a median baseline IPSS of 9.95. The median prescription isodose line was 68%. The median clinical follow-up was 35.49 months. Acute grade 1, 2, and 3 genitourinary toxicities occurred in 41.1%, 35.7%, and 0% of patients. All acute genitourinary toxicities resolved except 1 patient with grade 2 toxicity that progressed to grade 3 late toxicity. No dose-volume relationships were associated with acute genitourinary grade 2+ toxicity. Late grade 1, 2, and 3 genitourinary toxicity occurred in 19.6%, 19.6%, and 3.6% of cases, respectively. Of the cases with late toxicities, 16.7% were persistent. Late grade 2+ genitourinary toxicity was associated with prostate volume ≥50 mL, lower homogeneity index, and urethral maximum point dose ≥47 Gy. The overall risk of any grade 2+ genitourinary toxicity was associated with baseline IPSS >7, prostate volume ≥50 mL, urethral volume receiving 44 Gy, and bladder volume receiving 19 Gy. ConclusionsSBRT for prostate cancer appears well tolerated, with mostly transient low-grade toxicity. Urethral sparing should be used with a maximum point dose <47 Gy, volume receiving 120 Gy <50% of the prostate, and bladder volume receiving 19 Gy <15 mL in 4 fraction treatments. Patients with prostate volumes ≥50 mL should be counseled regarding the increased risk of moderate-grade genitourinary toxicity.

High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen.

We report a single-institution retrospective analysis of the outcomes, disease control, and toxicity of high-dose-rate (HDR) brachytherapy used as the only treatment modality (monotherapy) for localized prostate cancer. Between 2006 and 2012, 77 patients with diagnosed prostate cancer were treated with HDR brachytherapy as a monotherapy. The prescribed dose was 45Gy in three separate implants 21days apart, with single fraction per implant. Of the 77 patients, 67 (87%) received hormonal therapy. Prostate-specific antigen failure was defined according to Phoenix consensus, as nadir+ 2ng/mL. Toxicity was scored according to Common Terminology Criteria for Adverse Events, version 4.03. The median followup time was 57 months (4.75 years). The 5-year actuarial overall survival was 98.7%, biochemical control 96.7%, local control 96.9%, and metastasis-free survival 98.4%. Younger age at the beginning of brachytherapy predicted the onset of bounce phenomenon. There were no Grade 3 or higher acute toxicities detected, and Grade 2 genitourinary acute toxicity developed in 19 patients (24.6%). There were no Grade 2 gastrointestinal complications. No Grade 4 or 5 late toxicity was detected. There were also no Grade 3 gastrointestinal toxicities detected. One patient (1.3%) underwent transurethral resection of the prostate because of Grade 3 urethral stenosis and urinary retention. A total of 26 patients (33.8%) developed Grade 2 late toxicity. HDR brachytherapy as monotherapy for localized prostate cancer was feasible, effective, and had acceptable toxicity profile.

Chemotherapy and chemoprevention by thiazolidinediones.

Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

Dose-Volume Analysis of Urinary Toxicity Following SBRT Monotherapy for Prostate Cancer

Dose-Volume Analysis of Urinary Toxicity Following SBRT Monotherapy for Prostate Cancer

High-dose-rate brachytherapy as monotherapy for prostate cancer.

To review and analyze the published data on high-dose-rate brachytherapy as monotherapy in the treatment of prostate cancer. A literature search and a systematic review of the high-dose-rate (HDR) brachytherapy (monotherapy) prostate literature were performed on PubMed using "high-dose-rate, brachytherapy, prostate, monotherapy" as search terms. More than 80 articles and abstracts published between 1990 and 2013 were identified. Data tables were generated and summary descriptions created. Commentary and opinion was formulated through discussion and consensus based on the critical review of the literature and the author's combined personal experience and knowledge. Thirteen articles reported clinical outcome and toxicity with followup ranging from 1.5 to 8.0years. Results were available for all risk groups. A variety of dose and fractionation schedules were described. Prostate-specific antigen progression-free survival ranged from 79% to 100% and local control from 97% to 100%. The toxicity rates were low. Genitourinary toxicity, mainly frequency/urgency, was 0-16% (Grade 3). Gastrointestinal toxicity was 0-2% (Grade 3). Erectile function preservation was 67-89%. The radiobiological, clinical, and technical features of HDR brachytherapy were reviewed and discussed. Consistently high local tumor control and low complications rates are reported with HDR monotherapy. It provides reproducible high-quality dosimetry, it has an advantage from a radiobiology perspective, and it has a good radiation safety profile. HDR brachytherapy is a safe and effective local treatment modality for prostate cancer.

Biochemical and clinical outcomes after high-dose salvage radiotherapy as monotherapy for prostate cancer.

To retrospectively evaluate the role of high-dose salvage radiotherapy (SRT) alone with regard to biochemical and clinical outcomes in patients with biochemical failure (BF) after radical prostatectomy (RP). Between January 2003 and August 2011, 168 hormone-naïve localized prostate cancer patients received SRT alone for post-RP BF in a single institution and were retrospectively analyzed. Multivariate analysis was performed to determine the independent prognostic impact of clinical factors on biochemical and clinical outcomes [biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS) and overall survival (OS)]. Median follow-up was 54 months. Actuarial bRFS, cRFS, CSS and OS at 5 years were, respectively, 64, 86.2, 94.5 and 96.3 %. On multivariate analysis, nadir PSA (nPSA) after SRT was significantly associated with bRFS (HR 15, p = 0.001) and cRFS (HR 9, p = 0.001), while CSS was associated with RT dose (≥70 Gy; HR 1.9 p = 0.023), pre-RT PSA (<1.5 vs. ≥1.5 ng/mL; HR 1.3, p = 0.008) and age (>75 years; HR 1.2, p = 0.05). OS was significantly correlated with pre-SRT PSA (linear correlation; HR 1.1, p = 0.023) and age (<75 vs. ≥ 75 years; HR 1.1, p = 0.026). Effective biochemical and clinical control rates may be safely achieved administering SRT with high doses (≥72 Gy) and using conformal techniques, especially in older patients presenting with lower pre-SRT PSA values. A lower nPSA after SRT predicts for better 5 years bRFS and cRFS rates.

Toxicity Associated with High-Dose-Rate Monotherapy for Prostate Cancer

Toxicity Associated with High-Dose-Rate Monotherapy for Prostate Cancer

Definitive Multifraction High-Dose-Rate Monotherapy for Prostate Cancer Is Associated with Minimal Short-Term Toxicity and Improvement in Long-Term Urinary Function

Definitive Multifraction High-Dose-Rate Monotherapy for Prostate Cancer Is Associated with Minimal Short-Term Toxicity and Improvement in Long-Term Urinary Function

Six-Year Biochemical Outcome in Patients Treated with Cs-131 Brachytherapy as Monotherapy for Prostate Cancer

Cs-131 is a radioisotope with a half-life of 9.7 days that is being increasingly used for prostate brachytherapy (PB). Due to its shorter half-life than other radioisotopes, including I-125 and Pd-103, Cs-131 may be associated with a shorter duration of irritative urinary symptoms. The outcome data with this isotope is still maturing. We present the updated, intermediate-term outcome of patients treated with Cs-131 PB monotherapy.

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective.

High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. Although clinical results are not yet mature enough, it is a highly promising approach in terms of potential benefits for both radiation physics and radiobiology. In this article, we describe our technique for monotherapeutic HDR prostate brachytherapy, as well as the rationale and theoretical background, with educational intent.

Monotherapeutic high-dose-rate brachytherapy for prostate cancer: A dose reduction trial

PurposeTo report preliminary results of our second regimen with 45.5Gy/7 fractions aiming to reduce toxicity, compared with our first regimen with 54Gy/9 fractions, using high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer. Materials and methodsFrom 2005 through 2010, 63 patients with localized prostate cancer were treated with HDR brachytherapy alone in 45.5Gy/7 fractions for 4days. Thirty-four patients were considered as intermediate-risk and 29 as high-risk. Thirty-seven patients also received neoadjuvant and/or adjuvant hormonal therapy. Biologically effective dose assuming α/β=1.5Gy (BED1.5) was reduced from 270Gy to 243Gy, and BED3.0 from 162Gy to 144Gy, compared to previous 54Gy/9 fractions for 5days. ResultsMedian follow-up time was 42months (range 13–72). Grade 2 acute toxicities occurred in six (9.5%), late toxicities in five (7.9%) patients, and Grade 3 or higher in none. Grade 2 late gastrointestinal toxicity rate was 1.6%, compared with 7.1% for the 54Gy regimen. Three-year PSA failure-free rates for intermediate- and high-risk patients were 96% and 90%, which were comparable to 93% and 85% for the 54Gy regimen. ConclusionsCompared to the 54 Gy/9 fractions regimen, dose-reduced regimen of 45.5Gy/7 fractions using HDR brachytherapy as monotherapy preliminarily showed an equivalent or lower incidence rate for acute and late toxicities without compromising the excellent PSA failure-free rate. Further studies with more patients and longer follow-up are warranted.

HDR brachytherapy as monotherapy for prostate cancer: Preliminary toxicity data

HDR brachytherapy as monotherapy for prostate cancer: Preliminary toxicity data

Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

The emerging role of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer

High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1–4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high ‘biologically effective dose (BED)’ of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.