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Thread: (H) Radiation Treatment

  1. #121
    Clinical outcomes of external beam radiotherapy in patients with localized prostate cancer: Does dose escalation matter?



    To report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14-year period, and to determine the impact of dose escalation of prostate cancer outcomes.

    Patients with T1-T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5-year overall survival (OS). The secondary endpoints were 5-year freedom from biochemical failure (FFBF) and treatment toxicities.

    A total of 200 eligible patients were identified. Median follow-up duration was 48 months. 13%, 36% and 51% of patients had low-, intermediate- and high-risk disease. Median dose was 79.2 Gy. The 5-year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low-, intermediate- and high-risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95-10.08; P < 0.01).

    Men with localized prostate cancer treated with EBRT in our population had excellent 5-year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose-escalated EBRT.

  2. #122
    New approaches for effective and safe pelvic radiotherapy in high-risk prostate cancer



    Radical radiotherapy for prostate cancer offers excellent long-term outcomes for patients with high-risk disease. The increased risk of pelvic nodal involvement in this cohort has led to the development of whole-pelvis radiotherapy (WPRT) with a prostate boost. However, the use of WPRT remains controversial. Data are mixed, but advanced radiotherapy techniques enable delivery of increased radiation to pelvic nodes with acceptable levels of toxicity. Contemporary imaging modalities with increased sensitivity for detecting subclinical lymph node disease will facilitate selection of patients most likely to benefit from WPRT. Using such modalities for image guidance of advanced radiotherapy techniques could also permit high-dose delivery to nodes outside the conventional Radiation Therapy Oncology Group volumes, where magnetic resonance lymphography and single-photon-emission CT imaging have mapped a high frequency of microscopic disease. With increased toxicity a concern, an alternative to WPRT would be selective irradiation of target nodal groups most likely to harbour occult disease. New image-based ‘big data’ mining techniques enable the large-scale comparison of incidental dose distributions of thousands of patients treated in the past. By using novel computing methods and artificial intelligence, high-risk regions can be identified and used to optimize WPRT through refined knowledge of the likely location of subclinical disease.
    Key points

    • Prophylactic pelvic nodal irradiation in patients with high-risk prostate cancer might improve clinical outcomes.
    • Negative results in clinical trials to date might be attributable to subtherapeutic radiation doses, inappropriate patient selection and suboptimal field size delineation.
    • Conformal radiotherapy techniques reduce incidental pelvic lymph node dose, increasing the potential utility of whole pelvis radiotherapy (WPRT) in the modern intensity-modulated radiotherapy era.
    • Contemporary imaging modalities with high sensitivity for the detection of occult lymph node metastases will improve patient selection for WPRT and guide appropriate target volume definition.
    • Advanced radiotherapy techniques will permit dose escalation to minimally positive nodal regions, both inside and outside of the standard Radiation Therapy Oncology Group target volumes.
    • Large-scale image-based data mining raises the possibility of selective irradiation of statistically identified high-risk nodal groups to improve the therapeutic ratio in WPRT.

  3. #123
    Comparison of outcomes and toxicity between extreme and moderate radiotherapy hypofractionation in localized prostate cancer: a propensity score analysis



    To compare clinical outcomes and toxicities of two radiotherapy (RT) schemes for localized prostate cancer (PCa): the extremely hypofractionated (EH), 5 fractions of 6.5-7Gy to a total dose of 32.5-35 Gy, and the moderately hypofractionated (MH), 26 fractions of 2.7Gy to a total dose of 70.2 Gy. A propensity score method was used to compare the EH-RT and MH-RT groups.

    Patients and methods
    Our analysis included a total of 421 patients, divided in two groups: 227 treated with MH-RT, and 194 treated with EH-RT (43 and 30 months of median follow-up). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate Proportional Hazard Cox models were used to compare the two groups mainly for gastro-intestinal (GI) and genito-urinary (GU) toxicity, and secondarily for clinical progression free survival (cPFS), biochemical PFS (bPFS) and for overall survival (OS).

    Considering the whole population, acute GU and GI > Grade 1 was significantly more frequent in the whole MH-RT group (p<0.001 and 0.002 respectively). A borderline significantly greater late GU was confirmed by the multivariate analysis (P=0.07). Concerning tumor outcome, no statistically significant differences were observed. Following propensity score matching 226 patients were included in the analysis. The two obtained propensity score matched groups did not differ for any of the clinical and pathological variables considered for the analysis, resulting in well balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.

    EH-RT yield to a decreased risk of acute or late toxicities as compared to MH-RT and oncological outcomes were comparable. Based on our data, EH-RT might be considered as a treatment modality of choice for selected PCa patients.

  4. #124
    Thirty-day hospital revisits after prostate brachytherapy: who is at risk?
    [2019, Full Text]



    Transperineal prostate brachytherapy is a common outpatient procedure for the treatment of prostate cancer. Whereas long-term morbidity and toxicities are widely published, rates of short-term complications leading to hospital revisits have not been well described.

    Materials and methods
    Patients who underwent brachytherapy for prostate cancer in an ambulatory setting were identified in the Healthcare Cost and Utilization Project State Ambulatory Surgery Database for California between 2007 and 2011. Emergency department (ED) visits and inpatient admissions within 30 days of treatment were determined from the California Healthcare Cost and Utilization Project State Emergency Department Database and State Inpatient Database, respectively.

    Between 2007 and 2011, 9,042 patients underwent brachytherapy for prostate cancer. Within 30 days postoperatively, 543 (6.0%) patients experienced 674 hospital encounters. ED visits comprised most encounters (68.7%) at a median of 7 days (interquartile range 2–16) after surgery. Inpatient hospitalizations occurred on 155 of 674 visits (23.0%) at a median of 12 days (interquartile range 5–20). Common presenting diagnoses included urinary retention, malfunctioning catheter, hematuria, and urinary tract infection. Logistic regression demonstrated advanced age {65–75 years: odds ratio [OR], 1.3 [95% confidence interval (CI) 1.06–1.60, P = 0.01]; >75 years: OR 1.5 [95% CI 1.18–1.97, P = 0.001]}, inpatient admission within 90 days before surgery [OR 2.68 (95% CI 1.8–4.0, P < 0.001)], and ED visit within 180 days before surgery [OR 1.63 (95% CI 1.4–1.89, P < 0.001)] as factors that increased the risk of hospital-based evaluation after outpatient brachytherapy. Charlson comorbidity score did not influence risk.

    ED visits and inpatient admissions are not uncommon after prostate brachytherapy. Risk of revisit is higher in elderly patients and those who have had recent inpatient or ED encounters.

  5. #125
    High Dose Rate Brachytherapy versus Low Dose Rate Brachytherapy for the Treatment of Prostate Cancer: A Review of Clinical Effectiveness and Cost-Effectiveness
    [2019, Review, Full Text]


    Context and Policy Issues

    Prostate cancer is the most common cancer in Canadian adults with prostates and the fourth most common cancer across all Canadians.1 In 2017, there were an estimated 21,300 new cases of prostate cancer diagnosed in Canada and there were an estimated 4,100 deaths, representing 10% of all cancer deaths in Canadians with a prostate that year.1

    Radiation therapy is a standard option for the management and treatment of localized prostate cancer.2 When radiation is delivered using machines outside of the body it is referred to as external beam radiation therapy (EBRT)3 and when it is delivered internally by placing the source of radiation directly into the prostate gland near the tumour it is called brachytherapy.3 There are two types of brachytherapy: low-dose-rate (LDR) and high-dose-rate (HDR). LDR brachytherapy involves permanently or temporarily placing radioactive seeds in the prostate to deliver radiation over an extended period of time, while HDR involves inserting flexible needles into the prostate to deliver a high dose of radiation over a period of a few minutes.3 The total dose of radiation may be delivered as one treatment or divided over two or more treatments, called fractions.4

    Choice of treatment is based on factors including patient values and preferences, clinician judgement based on initial evaluation (e.g., identification of tumor stage, baseline serum prostate specific antigen levels [PSA], and Gleason score), and resource availability.3,5

    There is not currently direct clinical evidence supporting the superiority of HDR or LDR brachytherapy with respect to tumor control or reduced toxicity.

    Therefore, the purpose of this report is to summarize the evidence regarding the comparative clinical and cost-effectiveness of HDR versus LDR brachytherapy for the treatment of prostate cancer.

    Research Questions

    1. What is the comparative clinical effectiveness of high-dose-rate versus low-dose-rate brachytherapy for the treatment of prostate cancer?
    2. What is the cost-effectiveness of high-dose-rate versus low-dose-rate brachytherapy for the treatment of prostate cancer?

    Key Findings

    Evidence of limited to moderate quality from five non-randomized cohort studies suggested that there were no significant differences between LDR prostate brachytherapy and HDR prostate brachytherapy delivered as a monotherapy for relapse or serious adverse events. In contrast, LDR prostate brachytherapy was associated with significantly better relapse and serious adverse event profile than HDR brachytherapy when combined with External Beam Radiation Therapy (EBRT). Evidence of limited quality from one study showed that for HRQoL, LDR brachytherapy was either more favourable, less favourable, or did not differ from HDR brachytherapy monotherapy depending on the specific type of HRQoL being examined. The combined HDR and EBRT treatment option was not examined with respect to self-reported HRQoL. No evidence regarding the cost-effectiveness of high-dose-rate (HDR) brachytherapy was identified.

  6. #126
    Patient-reported health-related quality of life up to three years after the treatment with permanent brachytherapy: Outcome of the large-scale, prospective longitudinal study in Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS)



    To evaluate long-term health-related quality of life (HRQOL) impact of I-125 permanent seed implantation (PI) in Japanese patients with localized prostate cancer.

    This is a longitudinal, prospective study of 2353 patients who enrolled in the nationwide Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS) from July 2005 to June 2007. HRQOL was measured before and after treatment (3, 12, 24, and 36 months) using the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8 ) and the Expanded Prostate Cancer Index Composite Japanese version questionnaire.

    Of the total of 1511 patients who returned anonymized HRQOL questionnaires to Translational Research Center for Medical Innovation, 1079 underwent PI alone (PI group) and 432 underwent combined PI and external beam radiation therapy (EBRT) treatment (EBRT combination therapy group). The mental component summary score of SF-8 was improved at 12, 24, and 36 months compared with the pretreatment level. Although the urinary summary score at 3 months in the PI group was significantly lower than that in the EBRT combination therapy group, which recovered thereafter and was comparable to the score of the EBRT combination therapy group. The bowel summary score in the PI group was significantly higher than that in the EBRT combination therapy group at 12, 24, and 36 months.

    This longitudinal, large-scale prospective study indicated that the general HRQOL for PI was almost maintained 3 years after treatment. These results provide important information for patients with localized prostate cancer, who may select to receive I-125 brachytherapy.

  7. #127
    National practice patterns for lymph node irradiation in 197,000 men receiving external beam radiotherapy for localized prostate cancer



    Controversy surrounds the benefit of pelvic lymph node irradiation (PLN-RT) in localized prostate cancer (CaP). Our objective was to determine the practice patterns and predictors of PLN-RT in a national cohort.

    The National Cancer Data Base (2005-2015) was leveraged to obtain men diagnosed with nonmetastatic CaP treated with external beam radiotherapy (n = 197,378 ). Multivariable logistic regressions were used to assess temporal trends and factors associated with PLN-RT.

    PLN-RT occurred in 37% of patients overall, which increased to 41% by 2015. When stratified by risk group, there was no significant difference in PLN-RT over time in low, favorable intermediate, unfavorable intermediate, or high-risk CaP. PLN-RT increased for men with very high-risk disease (51%-60%; odds ratio per year 1.34, 95% confidence inrerval 1.06-1.70, P = 0.013). Increased odds of PLN-RT was associated with higher risk disease, addition of hormone therapy, treatment at community hospitals, and shorter patient travel distance to treatment facilities. Surprisingly, 26% and 34% of low and favorable intermediate risk CaP received PLN-RT, respectively. Predictors of PLN-RT among these patients included treatment at a community practice and use of brachytherapy or hormone therapy.

    PLN-RT occurred in about one-third of men receiving external beam radiotherapy and increased over time, mostly in men with very high-risk CaP for unclear reasons. Of concern, over one-quarter of low-risk men receive PLN-RT. Further work is needed to understand the heterogeneity in PLN-RT use. We await the completion of RTO G 09-24 to better understand the role of PLN-RT for men with localized CaP.

  8. #128
    Radiotherapy In The Definitive Management Of Oligometastatic Prostate Cancer: The Johns Hopkins Experience
    [2019, Full Text]



    The use of radiotherapy (RT) in consolidating oligometastatic prostate cancer (OPCa) is a rapidly evolving treatment paradigm. Here we review our institutional experience using metastasis directed therapy (MDT) in the definitive management of men with OPCa.

    OPCa treated with definitive RT were included. The Kaplan-Meier method and multivariable Cox regression analysis were performed to assess biochemical progression free survival (bPFS) and time to next intervention (TTNI). Cumulative incidence (CI) functions were used to calculate rates of local failure. Toxicity was assessed using CTCAE v4 criteria.

    This study analyzed 156 OPCa patients and 354 metastatic lesions with median follow-up (fup) of 24.6 months. Of 150 patients with toxicity data, 53 (35%) experienced acute grade 1 toxicity, 8 (5%) had grade 2, and none had grade 3 toxicity. Only 13 (9%) had late toxicities. At 24 months the CI of local failure was 7.4%. Median bPFS for the entire cohort was 12.9 months and 52% at one year. On multivariable analysis, factors associated with prolonged bPFS were peri-RT androgen deprivation (ADT), lower GTV, and hormone sensitive (HS) OPCa. Median TTNI, including repeat RT, was 21.6 months. Median bPFS for men with HSPC was 17.2 months compared to 7.2 months in men with castrate-resistant OPCa (CROPCa) (p <0.0001) and cumulative incidence of local failure at 24 months was lower with HSOPCa (4.8% vs 12.1%; p=0.034). We analyzed 28 men with HSOPCa treated with a course of peri-RT ADT (median 4.3 months) with recovery of testosterone. At median 33.5 month fup, 20 have not developed bPFS, median bPFS has not yet been reached, and 24 month bPFS was 77%.

    MDT can be effective across a wide ranges of OPCa subtypes, however with differential efficacy. Continued studies investigating the use of RT over the wide range of OPCa patients is warranted.

  9. #129
    Analysis of Spatial Dose-Volume Relationships and Decline in Sexual Function Following Permanent Brachytherapy for Prostate Cancer



    To explore relationships between dose to periprostatic anatomic structures and erectile dysfunction (ED) outcomes in an institutional cohort treated with prostate brachytherapy.

    The Sexual Health Inventory for Men (SHIM) instrument was administered for stage cT1-T2 prostate cancer patients treated with Pd-103 brachytherapy over a 10-year interval. Dose volume histograms (DVH) for regional organs at risk (OARs) and periprostatic regions were calculated with and without expansions to account for contouring uncertainty. Regression tree analysis clustered patients into ED risk groups.

    We identified 115 men treated with definitive prostate brachytherapy who had 2 years of complete follow up. On univariate analysis, the sub-apical region (SAR) caudal to prostate was the only defined region with DVH parameters significant for potency outcomes. Regression tree analysis separated patients into low ED risk (mean 2-year SHIM 20.03), medium ED risk (15.02), and high ED risk (5.54) groups. Among patients with good baseline function (SHIM ≥ 17), a dose ≥72.75 Gy to 20% of the SAR with 1cm expansion was most predictive for 2-year potency outcome. On multivariate analysis, regression tree risk group remained significant for predicting potency outcomes even after adjustment for baseline SHIM and age.

    Dose to the sub-apical region immediately caudal to prostate was predictive for potency outcomes in patients with good baseline function. Minimization of dose to this region may improve potency outcomes following prostate brachytherapy.
    [Emphasis mine]

  10. #130
    Stereotactic Ablative Radiotherapy for Prostate Cancer-The Treatment Results of 500 Patients and Analysis of Failures
    [2019, Full Text]



    Stereotactic ablative radiotherapy is a very promising approach for the treatment of patients with prostate cancer. The aim of this study was to evaluate the clinical tolerance, effectiveness, patterns of failure, and attempt to define predictive factors based on our experience.

    The cohort consists of 264 low-risk and 236 intermediate-risk consecutive patients treated at one institution. Prostate-specific antigen (PSA), adverse effects, and androgen deprivation therapy (ADT) usage were noted.

    Median follow-up was 31.3 months. Over 90% of the patients reported no gastrointestinal toxicity. There were 4 occurrences of G3+ sequelae. 75% patients had no genitourinary toxicity at first month, and up to 90% during the rest of follow-up, with only 1 case of G3 adverse event. The toxicity was more pronounced in patients with higher PSA concentrations. Prior to stereotactic ablative radiotherapy, the mean PSA was 7.59 and 277 patients used ADT. The PSA decreased for up to 20 months before reaching a plateau. The decline was slower, and PSA levels were higher in patients without ADT. A total of 15 treatment failures occured in a median time of 19.9 months. Higher PSA concentrations were connected with higher failure rates, even in the first month and prior to reaching Phoenix criterion.

    CyberKnife-based stereotactic ablative radiotherapy of low-risk and intermediate-risk prostate cancer patients is an effective and well-tolerated modality of treatment. PSA is the most important predictive factor. The evolution of PSA concentration in a particular subgroup of patients suggests that ADT in intermediate-risk cases could improve long-term results.


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