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Thread: (H) Radiation Treatment

  1. #101
    Long-term biochemical progression-free survival following brachytherapy for prostate cancer: Further insight into the role of short-term androgen deprivation and intermediate risk group subclassification
    [2019, Full Text]



    Brachytherapy is a well-established treatment of localized prostate cancer. Few studies have documented long-term results, specifically biochemical progression-free survival (bPFS) in men with brachytherapy alone, with or without short-term androgen deprivation therapy (ADT), or in combination with external beam radiotherapy (EBRT). Our aim was to analyze long-term bPFS of brachytherapy treated patients.

    Materials and methods
    Retrospective analysis of 1457 patients with low and intermediate risk prostate cancer treated with brachytherapy alone (1255) or combined with EBRT (202). Six-months ADT was administrated for all EBRT combined patients and for prostate volume downsizing when >55 cc (328 ). Failure was by the Phoenix definition. Kaplan-Meier analysis and multivariate Cox regression estimated and compared 10-yr and 15-yr rates of bPFS.

    Median follow-up was 6.1 yr. Ten and 15-yr bPFS rates of the entire cohort were 93.2% and 89.2%, respectively. On multivariate analysis, PSA density (PSAD), ADT and clinical stage were significantly associated with failure. The most powerful independent factor was PSAD with a HR of 3.5 (95% CI, 1.7–7.4) for PSAD above 0.15. No significant difference was found between low and intermediate risks patients regardless of treatment regimen. However, comparison of two intermediate risk groups, Gleason score (GS) 7, PSA<20 ng/ml versus GS≤6 and PSA = 10–20 ng/ml, revealed 10- and 15-yr bPFS rates of 94.2% and 94.2% compared to 88.2% and 79.9%, (P = 0.022), respectively. ADT improved bPFS rates in low risk patients. The ten and 15-yr bPFS rates were 97.6% and 94.6% compared to 92.3% and 88.2%, (P = 0.020), respectively.

    Our retrospective large scale study suggests that brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Combination of brachytherapy with EBRT yields favorable outcomes in GS 7 intermediate risk patients and short-term ADT has a positive effect on outcomes in low risk patients.

    Further prospective studies are warranted to discriminate the role of adding either EBRT and/or ADT to brachytherapy protocols.

  2. #102
    Impact of Cribriform Pattern and Intraductal Carcinoma on Gleason 7 Prostate Cancer Treated with External Beam Radiotherapy



    To assess the impact of cribriform pattern and/or intraductal carcinoma (IDC) on Gleason 7 prostate cancer (PCa) treated with external beam radiotherapy (EBRT).

    We evaluated men with Gleason 7 (Grade Group 2 and 3) PCa treated with dose-escalated EBRT +/- androgen deprivation, and reviewed biopsies for the presence of cribriform pattern and/or IDC. Endpoints included biochemical recurrence free survival (BRFS), distant metastasis free survival (DMFS), and disease specific survival (DSS).

    Of 237 patients, median follow up was 117 months (range 3-236), and NCCN risk group was 24% favorable-intermediate risk, 53% unfavorable-intermediate risk, and 23% high risk. Rates of cribriform pattern without IDC, cribriform pattern with IDC, IDC without cribriform pattern, and neither morphology, were 36%, 13%, 0%, and 51%, respectively. On multivariable analysis (MVA), presence of cribriform pattern with IDC (HR 4.22; 95% CI 2.08-8.53; p<0.0001), PSA 10-20 ng/ml (1.97; 1.03-3.79; p=0.04), and PSA >20 ng/ml (2.26; 1.21-4.23; p=0.01) were associated with worse BRFS. On MVA, only cribriform pattern with IDC was associated with inferior DMFS (4.18; 1.43-12.28; p=0.01) and DSS (14.26; 2.75-74.04; p=0.0016). Factors associated with having cribriform pattern +/- IDC included Grade Group 3, high risk group, and ≥50% positive biopsy cores. When stratified by neither morphology present, cribriform pattern without IDC, and cribriform pattern with IDC, differences in BRFS (p=0.00042), DMFS (p=0.017), and DSS (p<0.0001) were statistically significant.

    Cribriform pattern with IDC was associated with adverse outcomes among men with Gleason 7 PCa treated with ERBT, whereas cribriform pattern without IDC was not. Future studies may benefit from dichotomizing these two histologic entities.

  3. #103
    Salvage radical prostatectomy for recurrent prostate cancer: morbidity and functional outcomes from a large multicenter series of open versus robotic approaches [2019]




    Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP have demonstrated improved results. In this study, we assessed sRP functional outcomes and complications, comparing robotic and open approaches.

    We retrospectively collected data of sRP for recurrent prostate cancer (PCa) after local non-surgical treatment at 18 tertiary referral centers, from 2000 to 2016. The Clavien-Dindo classification was employed to classify complications. Complications and functional outcomes were evaluated in a uni- and multivariable analysis.

    We included 395 sRP (n=186 open; n=209 robotic). The robotic-sRP yielded lower BL (p<0.0001) and shorter HS (p<0.0001). No significant differences emerged in major (10.1%, p=0.16) and overall complications (34.9%, p=0.67), including an overall low risk of rectal injuries and fistulas (1.58% and 2.02% respectively); however, anastomotic stricture was more frequent for open-sRP (16.57% vs 7.66%; p<0.01). Overall 24.6% had severe (≥3pads/day) incontinence (12 or 6mo). On multivariable analysis robotic-sRP was an independent predictor for continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature and absence of standardized surgical technique.

    In a contemporary series, sRP showed a low risk of major complications and better functional outcomes than previously reported. Robotic-sRP may reduce anastomotic strictures, blood loss, and hospital stay, and improve continence outcomes.

  4. #104
    Current status of intensity‐modulated radiation therapy for prostate cancer: History, clinical results and future directions
    [2019, Full Text]



    External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity‐modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity‐modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity‐modulated radiation therapy is image‐guided radiation therapy. The clinical benefit for prostate image‐guided radiation therapy has been assessed by comparing the outcomes of patients with either the image‐guided radiation therapy or non‐image‐guided radiation therapy technique. These studies have shown that image‐guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta‐analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity‐modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity‐modulated radiation therapy, new techniques for intensity‐modulated radiation therapy, hypofractionation and future directions for prostate cancer.

  5. #105
    Are we ready for a paradigm shift from high-dose conventional to moderate hypofractionated radiotherapy in intermediate-high risk prostate cancer? A systematic review of randomized controlled trials with trial sequential analysis



    to evaluate efficacy and late toxicity of moderate hypofractionated (HFRT) over high-dose (>76 Gy) conventional radiotherapy (CRT) in a non-inferiority perspective.

    Randomized controlled trials (RCTs) were included. HFRT regimens were deemed non-inferior to high-dose CRT if the computed CI for the overall RR did not exceed the non-inferiority margin of 7%.

    When the prespecified margin, corresponding to a critical RR of 0.930 for CCS, OS and BFS, was used all efficacy outcomes satisfied the criteria for the non-inferiority analysis indicating the non-inferiority of HFRT regimens over high-dose CRT in the medium term period. Differently, the evidence concerning the late toxicity was inconclusive.

    Noninferiority analysis indicates that moderate HFRT regimes are non-inferior over high-dose CRT in the medium-term. Inconclusive is the evidence for the late toxicity. Longer follow-up will provide a more clear answer concerning the non-inferiority of HFRT regimens in the long-term period.
    [Emphasis mine]

  6. #106
    Testosterone Levels and Sexual Quality of Life Following Stereotactic Body Radiotherapy for Prostate Cancer: A Multi-Institutional Analysis of Prospective Trials



    The impact of higher scatter doses per fraction on testicular function and quality of life following prostate SBRT is poorly studied.

    636 patients treated with SBRT for low- to intermediate-risk PCa from 2009-2014 were included. Changes in testosterone and in sexual and hormonal domain scores on the Expanded Prostate Composite Index-26 (EPIC) questionnaire over a 24-month period were evaluated via a one-sided t-test. EPIC score changes were evaluated in comparison with a distribution-based minimal clinically important difference (MCID) threshold, wherein changes of >1/2 or >1/3 the standard deviation in each domain were considered as medium-sized or small-sized effects, respectively.

    Median and mean percent changes in testosterone at the 3-6 month, 7-12 month, 13-18 month, and 19-24 month time-periods were -13.41% and -4.49% (p = 0.02);-12.23% and -2.77% (p = 0.13); -11.20% and -0.29% (p =0.47); -5.00% and +1.20% (p = 0.65). When analyzed after dividing the cohort into 3 groups based on baseline testosterone values using tertiles, testosterone tended to increase in patients in the 1st group and decrease in patients in the 3rd group. Overall, the decline in EPIC hormonal domain scores never exceeded the threshold for a small-sized effect, though the decline in EPIC sexual domain scores did pass this threshold at the 19-24 month time-period (mean 10.90 point decline). This decline was not present when groups were examined individually.

    In this large cohort of prospectively followed patients there was a transient decline in testosterone shortly after SBRT that normalized by 24 months post-treatment. There was no significant change in EPIC hormonal domain scores. A significant decline in EPIC sexual domain scores, consistent with a small-sized clinically detectable difference, manifested between 19-24 months of follow-up. These results are consistent with testosterone decline patterns and sexual function changes seen after other forms of photon-based radiotherapy.

  7. #107
    Quality of life after external beam radiotherapy for localized prostate cancer: Comparison with other modalities
    [2019, Review, Full Text]



    In external beam radiotherapy for localized prostate cancer, acute toxicities are typically transient and mild. These symptoms will disappear within 4–8 weeks after external beam radiotherapy. Some patients might suffer from proctitis with bloody stools as late rectal toxicity. Therefore, it has been shown that external beam radiotherapy has a more pronounced negative impact on bowel function compared with other treatment modalities. However, the recent development of modern beam delivery techniques, including intensity‐modulated radiotherapy, allows us not only to deliver higher doses to the prostate, but also to decrease the doses to the critical organs, resulting in the maintenance of patients’ quality of life within satisfactory levels. Patients’ quality of life after external beam radiotherapy is also strongly related to the total dose, fractionation regimens, dose parameters of the critical organs and treatment plan quality, with a trade‐off between the radicality of external beam radiotherapy and potentially increased toxicity. Radiation oncologists should choose treatment parameters carefully to achieve a reasonable balance between a good oncological outcome and the patient's quality of life.
    Last edited by DjinTonic; 05-30-2019 at 08:24 PM.

  8. #108
    Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials



    We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored.

    The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis.

    In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS.

    The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

  9. #109
    Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study



    To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era.

    Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate  seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT.

    The median follow-up time was 5.9 years (range 0.4-18.2 years); 5‑year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10.

    Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

  10. #110
    Treatment-Related Toxicity Using Prostate-Only Versus Prostate and Pelvic Lymph Node Intensity-Modulated Radiation Therapy: A National Population-Based Study



    There is a debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation for the treatment of men with high-risk prostate cancer. This study compared the toxicity of intensity-modulated radiation therapy (IMRT) to the prostate and the pelvic lymph nodes (PPLN-IMRT) with prostate-only IMRT (PO-IMRT).

    Patients with high-risk localized or locally advanced prostate cancer treated with IMRT in the English National Health Service between 2010 and 2013 were identified by using data from the Cancer Registry, the National Radiotherapy Dataset, and Hospital Episode Statistics, an administrative database of all hospital admissions. Follow-up was available up to December 31, 2015. Validated indicators were used to identify patients with severe toxicity according to the presence of both a procedure code and diagnostic code in patient Hospital Episode Statistics records. A competing risks regression analysis, with adjustment for patient and tumor characteristics, estimated subdistribution hazard ratios (sHRs) by comparing GI and genitourinary (GU) complications for PPLN-IMRT versus PO-IMRT.

    Three-year cumulative incidence in the PPLN-IMRT (n = 780) and PO-IMRT (n = 3,065) groups was 14% for both groups for GI toxicity, and 9% and 8% for GU toxicity, respectively. Patients receiving PPLN-IMRT and PO-IMRT had similar levels of severe GI (adjusted sHR, 1.00; 95% CI, 0.80 to 1.24; P = .97) and GU (adjusted sHR, 1.10; 95% CI, 0.83 to 1.46; P = .50) toxicity rates.

    Including PLNs in radiation fields for high-risk or locally advanced prostate cancer is not associated with increased GI or GU toxicity at 3 years. Additional follow-up is required to answer questions about its impact on late GU toxicity. Results from ongoing trials will provide insight into the anticancer effectiveness of PLN irradiation.


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