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Thread: (H) Radiation Treatment

  1. #141
    Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy



    To compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer.

    425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds.

    After a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions.

    After CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.

  2. #142
    A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy
    [2019, Full Text]



    There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR-EBRT) and high dose rate brachytherapy (HDR-EBRT) to treat intermediate and high risk prostate cancer.

    Men with intermediate and high risk prostate cancer treated using LDR-EBRT (treated between 1996 and 2007) and HDR-EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS).

    116 men were treated with LDR-EBRT and 171 were treated with HDR-EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR-EBRT cohort and 77.6% for the HDR-EBRT cohort. On multivariable analysis, patients treated with HDR-EBRT were more than twice as likely to experience biochemical progression compared with LDR-EBRT (HR 2.33, 95% CI 1.12-4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26-23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR-EBRT and HDR-EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance.

    LDR-EBRT may provide more effective PSA control at 5 years compared with HDR-EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further.

  3. #143
    Hypofractionation in Prostate Cancer Using Proton Beam
    [2019, Editorial, Full Text]


    Prostate cancer is the most prevalent cancer among men, with an estimated 175,000 new diagnoses in the United States in 2019. A variety of treatment options are available, including active surveillance, radiation therapy, or radical prostatectomy. The choice of treatment modality is based on a number of considerations: risk group, age, comorbidities, and performance status. Shared decision making and informed consent plays a pivotal role in the type of treatment a patient pursues. Patients must understand not only the cancer-related outcomes for their particular situation, but also the anticipated side effects of treatment.

  4. #144
    Radiation Therapy for Prostate Cancer


    (Dr. D'Amico is a co-author)


    Randomized controlled trials provide evidence-driven clinical decision making in the management of newly diagnosed nonmetastatic and oligometastatic prostate cancer. Advances in technology (eg, multiparametric MRI, MR/transrectal ultrasound fusion biopsy, image-guided radiation therapy, stereotactic body radiation therapy) have transformed diagnosis and treatment of prostate cancer while improving cancer control and quality-of-life outcomes. Exciting breakthroughs are revealing possible new indications for radiotherapy, particularly with respect to oligometastatic prostate cancer. Ongoing studies using next-generation androgen receptor–targeted agents hold promise to continue to improve important clinical outcomes, including metastasis-free prostate cancer–specific and overall survival in addition to health-related quality of life.

    • Men with very low-risk or low-risk prostate cancer (PC) should be considered for active surveillance; however, notable exceptions are discussed.
    • Favorable intermediate-risk PC may be best treated with monotherapies, whereas unfavorable intermediate risk PC may be best treated with high-dose radiation therapy (RT) 1 short-course androgen deprivation therapy (ADT) (4–6 months).
    • High-risk PC should be treated with a multimodality approach. Radiotherapeutic treatment of the prostate in men with limited oligometastatic PC should be discussed.
    • Indications for adjuvant postoperative radiation are pT3a, pT3b, and R1. Whether adjuvant is superior to salvage therapy is unknown. Salvage treatment includes RT 1 ADT.
    • Given disparate results, predictive markers are needed to define the role of docetaxel in managing high-risk PC. Abiraterone may be indicated in N1M0 PC.
    [Emphasis mine]

  5. #145
    Stereotactic beam radiotherapy for prostate cancer: is less, more?
    [2019, Editorial, Full Text]

    The proportion of moderate gastrointestinal toxicity was higher than those reported by some phase 2 trials using similar stereotactic body radiotherapy scenarios, with proportions ranging from 2% to 8%.2, 3, 4 To reduce the dose to the rectal wall, the use of gadgets such as endorectal balloons or spacers implanted between the rectum and the prostate have been recommended.5, 6 Because both procedures are invasive or, at least, uncomfortable, an alternative could be to reduce the dose constraints applied to the rectal wall while keeping the dose prescription to the target unchanged. This method might lead to an optimisation of the final treatment plan by substantially reducing the intermediate and low doses to the rectal wall.7 Nowadays, dose distribution optimisation can be substantially and easily improved with software for multicriteria optimisation planning, based on Pareto surface.8
    Because the prostatic urethra inside the target volume always gets the full prescribed dose, the proportion of patients with moderate genitourinary acute toxic effects was similar to that which has been reported elsewhere (2635%).2, 3 Nevertheless, in the only trial with a similar treatment schedule, but a dose reduction to the urethra (from 725 Gy to 65 Gy per fraction), only 14 (17%) of 82 patients had moderate acute genitourinary toxic effects, which favourably compares with the 29% reported by Brand and colleagues.4 On the other hand, Zelefsky and colleagues reported genitourinary toxic effects in 24 (18%) of 136 patients, without reducing the dose to the urethra in their dose escalation trial from 325 Gy to 40 Gy in five fractions, thus casting doubts about the rationale for partially shielding the urethra, considering, additionally, an increased risk of local relapse.9
    Five fractions delivered every other day (approximately 10 days overall treatment time) has been the most frequently used schedule in most phase 2 trials of stereotactic body radiotherapy, regardless of the fact that the most convenient procedure for patients and department logistics would be to deliver stereotactic body radiotherapy 5 days in a row. Although no difference in severe genitourinary acute toxicity was observed among the 86 patients treated up to 1 week compared with the 329 treated in more than 1 week, Brand and colleagues1 found that genitourinary grade 2 acute toxicity was less among those patients treated in the shortest overall treatment time. Was this observation related to selection biases (patients with large prostatic volumes or less favourable baseline genitourinary symptoms being treated over a longer overall treatment time)? Nonetheless, this observation is an invitation to shorten the overall treatment time for stereotactic body radiotherapy in five fractions as much as possible.
    Patients in the stereotactic body radiotherapy group were treated with either CyberKnife or volumetric modulated arc radiotherapy. The irradiation time of each fraction was significantly different, much longer (45 min) with CyberKnife and much shorter with volumetric modulated arc radiotherapy (35 min). This difference might have had an effect on the incidence of acute toxicity, as was observed in this trial. Furthermore, research has suggested that a long beam-on time with CyberKnife might favour intrafraction repair mechanisms, thus reducing the biologically effective dose for late-responding tissues with high fractionation sensitivity.10 This effect might have consequences regarding tumour control and late effects in later follow-up.
    Finally, can the number of fractions with stereotactic body radiotherapy further be reduced from five to a single high-dose fraction? There are currently two ongoing monotherapy studies exploring the role of single-fraction stereotactic body radiotherapy for patients with localised prostate cancer: the PROSINT-IGRT phase 2 trial (NCT02570919) investigating 45 Gy in five consecutive fractions versus a single dose of 24 Gy; and the ONE-SHOT trial (NCT03294889), a phase 12, multicentre study of the safety and efficacy of a single fraction of 19 Gy with a urethra-sparing approach. Indeed, a change of paradigm towards radiosurgery for prostate cancer seems to be on its way.

  6. #146
    Quantitative MRI changes during weekly ultra-hypofractionated prostate cancer radiotherapy with integrated boost [2019]


    Purpose: Quantitative MRI reflects tissue characteristics. As possible changes during radiotherapy may lead to treatment adaptation based on response, we here assessed if such changes during treatment can be detected.

    Methods and Materials: In the hypoFLAME trial patients received ultra-hypofractionated prostate radiotherapy with an integrated boost to the tumor in 5 weekly fractions. We analyzed T2 and ADC maps of 47 patients that were acquired in MRI exams prior to and during radiotherapy, and performed rigid registrations based on the prostate contour on anatomical T2-weighted images. We analyzed median T2 and ADC values in 3 regions of interest (ROIs): the central gland (CG), peripheral zone (PZ) and tumor. We analyzed T2 and ADC changes during treatment and compared patients with and without hormonal therapy. We tested changes during treatment for statistical significance with Wilcoxon signed rank tests. Using confidence intervals as recommended from test-retest measurements, we identified persistent T2 and ADC changes during treatment.

    Results: In the CG, median T2 and ADC values significantly decreased 12% and 8% respectively in patients that received hormonal therapy, while in the PZ these values decreased 17% and 18%. In the tumor no statistically significant change was observed. In patients that did not receive hormonal therapy, median ADC values in the tumor increased with 20%, while in the CG and PZ no changes were observed. Persistent T2 changes in the tumor were found in 2 out of 24 patients, while none of the 47 patients had persistent ADC changes.

    Conclusions: Weekly quantitative MRI could identify statistically significant ADC changes in the tumor in patients without hormonal therapy. On a patient level few persistent T2 changes in the tumor were observed. Long-term follow-up is required to relate the persistentT2 and ADC changes to outcome and evaluate the applicability of quantitative MRI for response based treatment adaptation.
    This was a feasibility study to see if MRI changes can be detected during RT. It appears they can be. It remains to be seen how these changes correlate with treatment efficacy and whether in the future such changes can be used to modify the RT treatment during the time it is administered.

  7. #147
    Seven or less Fractions is Not the Standard of Care for Intermediate-Risk Prostate Cancer
    [2019, Review, Full Text]



    Evidence is accumulating for seven and less fractions in localised prostate cancer, including one large randomised trial. However, there is much more evidence yet to come and changing practice in advance of this may be premature. We review the reasons to persist with moderate hypofractionation for prostate cancer radiotherapy, until the results of further phase III studies are known.
    See also:

    Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials [2019, Full Text]



    Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

    Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses.

    The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93–1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42–3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76–1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12–2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61–0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89–1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86–1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups.

    Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.
    Last edited by DjinTonic; 11-12-2019 at 03:09 PM.

  8. #148
    HDR Prostate Brachytherapy
    [2019, Review, Full Text]


    Brachytherapy has become an essential pillar in all-stages of localized prostate cancer, where dose escalation has been demonstrated to improve outcome. HDR brachytherapy has evolved over the decades to be administered in 1-2 fractions. As either monotherapy or in combination with external beam, it offers many advantages over other treatment alternatives. Precise control over dose delivery allows focal dose escalation while sculpting dose around critical organs to maintain excellent tolerance. The high dose per fraction exploits the low α/β ratio of prostate cancer and triggers transcriptional changes in the tumor genome enhancing radiation sensitivity. We review the development, patient selection and results, and describe in detail the techniques for HDR brachytherapy.

  9. #149
    High Dose Rate Brachytherapy in High-Risk Localised Disease – Why Do Anything Else?



    The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains an important component of management, for those receiving radiotherapy, optimal local treatment should include a brachytherapy boost. This may be given by low dose rate (LDR) or high dose rate (HDR) techniques, but HDR has several advantages over LDR by virtue of more consistent dose optimisation, ability to treat outside the prostate and lower toxicity. A significant body of evidence now supports the use of HDR brachytherapy in addition to supplementary pelvic external beam radiotherapy for men with high-risk disease. Consistent evidence has emerged from randomised clinical trials, meta-analyses, and from institutional and multicentre cohort studies. It has been shown to improve local disease control and possibly reduce metastases and improve cancer-specific survival compared with external beam radiotherapy alone. It should be considered as standard treatment.

  10. #150
    Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis



    Recent studies have demonstrated both safety and efficacy of stereotactic body radiation therapy (SBRT) as monotherapy in the treatment of low and intermediate risk prostate cancer. Our study aims to provide an update analyzing the use of SBRT compared with conventional and hypofractionated regimens in the United States from 2004 to 2015.

    This retrospective review was conducted using the National Cancer Database. We identified 114,931 patients with sufficient diagnostic and treatment information treated with definitive radiation therapy in the United States from 2004 to 2015. The relative utilization of conventional fractionation (defined as 180–200 cGy per fraction and >5 fractions), moderate hypofractionation (defined as >200 cGy per fraction and >5 fractions), and SBRT (defined as >200 cGy per fraction and 5 fractions or less) were compared over the same time period. Logistic regression models were used to estimate trends. Demographic factors were collected and analyzed using chi-squared tests and independent t-tests.

    The proportion of prostate cancer patients receiving SBRT increased substantially from 0.9% in 2004 to 19.5% in 2015. Moderate hypofractionation exhibited some growth, increasing from 2.7% of patients to 4.7% in 2015. Conventional fractionation use declined significantly from 96.3% in 2004 to 75.8% in 2015. Notably, there was a sharp decline in the absolute number of patients receiving conventional fractionation in 2011, from 14,699 patients treated in 2009 to 1492 in 2011. Patients treated with SBRT were more likely to be treated in academic centers, younger, and have higher income than other fractionation groups. The most frequently used fractionation schedule was 3625 cGy in five fractions.

    The use of SBRT for low and intermediate risk prostate cancer has increased significantly from 2004 to 2015, coinciding with recently published data supporting the efficacy and favorable toxicity profile of this technique.


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