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Thread: (H) Radiation Treatment

  1. #81
    Hypofractionation in prostate cancer radiotherapy
    [2018, Review, Full Text]


    Abstract: Animal and clinical experiments in France in the 1920’s suggested that radiotherapy delivered in a number of daily dose fractions, spread out over a period of several weeks, resulted in better tumor control for a given level of normal tissue toxicity than the application of the radiation in a single large dose. In the 1980’s it was shown that there is a systematic difference in the fractionation dependence of late responding normal tissues and early responding tissues both normal and malignant, probably due to a difference in the proportion of dividing cells. In 1999, it was pointed out that, while this was true of most tumors, it was generally not the case for prostate cancer because it is particularly slow growing. Using data from both external beam radiotherapy and brachytherapy it was shown that prostate cancer responds to fractionation in a manner more similar to a late responding tissue than an early responding tissue. This led to the conclusion that much smaller numbers of fractions than usually used (with an appropriately reduced total dose) should be equally effective in treating prostate cancer, but with the associated advantages in cost, logistics and patient convenience. Many large scale randomized clinical trials have been completed in the past 18 years to test this concept, the conclusion being that that moderate hypofractionation, typically involving 15 to 25 fractions with doses per fraction of 2.5 to 3.5 Gy, is not inferior to conventional fractionation patterns involving 40 to 45 fractions with doses per fraction around 2 Gy. More recently extreme hypofractionation is being investigated, typically involving 4 to 7 fractions with much higher doses per fraction. It is too early to draw conclusions about extreme hypofractionation, but early toxicity results raise concerns.
    Last edited by DjinTonic; 01-03-2019 at 09:20 PM.

  2. #82
    Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline Summary
    [2018, Full Text]

    Guideline Summary


    External beam radiation therapy (EBRT) is a standard definitive treatment option for men with localized prostate cancer and confers long-term prostate cancer control outcomes equivalent to radical prostatectomy.1 Improvements in imaging and computing over the past two decades have led to a number of technical advances in planning and delivery of prostate EBRT. Notably, these include the use of cross-sectional imaging for treatment planning2 and innovations in treatment delivery, including intensity modulation3 and daily image guidance.4 These technical advances have permitted more precise and conformal delivery of escalated doses of radiation to the prostate, thereby improving the therapeutic ratio.

    Classically, the probability of cell survival after a dose of ionizing radiation is governed by the linear-quadratic model. In this model, curves of cell survival as a function of dose have an initial linear component followed by a steeper quadratic component. The relative weighting of each component, and thus the sensitivity to fractionation of the irradiated tissue, is characterized by a parameter called the alpha-beta ratio. The alpha-beta ratio of adenocarcinoma of the prostate is considered low compared with most other neoplasms, with several estimates derived from large populations in the range of 1 to 2 Gy.5-7 Unlike other solid tumors with higher alpha-beta ratios, the alpha-beta ratio of the adjacent dose-limiting normal structure, namely, the rectum, has been estimated to be greater than that of prostate cancer itself.8,9 An implication of this relationship is that hypofractionation—daily delivery of EBRT with fraction sizes greater than 2 Gy—may further improve the therapeutic ratio of EBRT in localized prostate cancer. Specifically, according to the model, for courses of conventionally fractionated and hypofractionated EBRT that are isoeffective, the hypofractionated regimen would be expected to produce somewhat less toxicity. For courses of conventionally fractionated and hypofractionated EBRT that are isotoxic, the hypofractionated regimen would be expected to be somewhat more effective.

    Given the radiobiologic considerations, hypofractionated EBRT has been intensively studied by numerous institutions and cooperative groups in prospective clinical trials in localized prostate cancer. Over the past 2 years, several large randomized controlled trials comparing conventional fractionation (1.8 to 2 Gy per fraction) with moderate hypofractionation (2.4 to 3.4 Gy per fraction) have been published. At the same time, population-based studies have observed an increasing use in routine practice of ultrahypofractionated EBRT (≥ 5 Gy per fraction).10 In this context, the American Society for Radiation Oncology, in collaboration with the American Society of Clinical Oncology and the American Urological Association, initiated development of an evidence-based clinical practice guideline on the use of hypofractionated EBRT in localized prostate cancer.
    See the Bottom Line

  3. #83
    Radiation Protection Responsibility in Brachytherapy



    Radiation protection in brachytherapy entails protecting members of the public, radiation professionals, and the patient from unnecessary radiation, as well as making sure that the radiation used in the patient's treatment is placed correctly with the correct dose distribution. Protecting members of the public from radiation emanating from brachytherapy sources implanted in a patient was an issue several decades ago, but with modern brachytherapy, the problem has mostly disappeared. The most frequent treatments are either low-dose-rate permanent implants for prostate cancer, or high-dose-rate procedures for gynecological, breast, or skin cancers. Almost all current permanent implants use low-energy photon sources that are shielded by the patient. Similarly, some temporary implants, such as eye plaques that also use low-energy photon sources, incorporate a metallic shield into the applicator. All high-dose-rate brachytherapy takes place in a treatment vault, in a manner similar to external-beam radiotherapy, thus eliminating exposure to members of the public, in the absence of some terrible error or mistake. Modern brachytherapy techniques either eliminate or greatly reduce radiation exposures to the brachytherapy staff also. As noted above, high-dose-rate treatments take place in a heavily shielded vault, and staff remain outside the vault when the source is out of its shielded housing. For low-energy permanent implants, facilities often order the sources loaded into the implant needles by the vendor, reducing the time the procedure staff is exposed to the source. Often, the loaded needles can be shielded while awaiting implantation. Alternatively, individual sources may be placed using a special applicator that shields the staff. Radiation protection of the patient in many respects differs little from how it was decades ago except for greatly increased precision. Assaying the strength of a source of any kind is still essential. As important as verifying the source strength is ensuring that the source will be in the correct location for the desired time. Imaging serves as the main mechanism to guide the implantation and verify source or applicator position. Modern imaging has unveiled anatomy exquisitely and often permits definition of target disease and neighboring normal structures sufficiently to allow very conformal dose distributions. Despite these great advances and capabilities, errors and mistakes (together called failures) still occur. Failures in health care overall are the third leading cause of death in the United States. Most treatment failures result not from equipment problems but from procedures gone wrong. Attention to comprehensive commissioning of both equipment and procedures and risk-based development of quality management procedures helps protect the patient. Patient safety organizations, established by the Agency for Healthcare Research and Quality, work with client facilities to help identify weaknesses in both treatment procedures and quality management and to develop improvements to enhance protection.
    Last edited by DjinTonic; 12-27-2018 at 02:22 PM.

  4. #84
    Impact of staging 68Ga-PSMA-11 PET scans on radiation treatment plans in patients with prostate cancer [



    To evaluate the impact of staging 68Ga-PSMA-11 PET imaging on radiotherapy (RT) dose and volumes in patients with prostate cancer.

    Forty-five patients (89% high or very high-risk by NCCN criteria) who underwent 68Ga-PSMA-11 PET imaging prior to definitive treatment for prostate cancer between December 2015 and December 2016 were included. Locations of 68Ga-PSMA-11-avid lesions were compared to RTOG consensus pelvic nodal volumes (clinical target volume, CTV); coverage of lesions outside the consensus CTV was considered a major change, while dose-escalation to lesions within the consensus CTV was considered a minor change.

    All patients had 68Ga-PSMA-11 PET uptake in the prostate. 25 patients (56%) had N1/M1a disease on 68Ga-PSMA-11 PET scan, of whom 21 (47%) were previously N0. Six patients (13%) had bone metastases on 68Ga-PSMA-11 PET scan, of whom four had prior negative bone scans. 8 patients (18%) had lymph node metastases outside the consensus CTV. 12 patients (27%) received a RT boost to nodes within the consensus CTV. 6 patients (13%) had limited bone metastases treated with focal RT. Overall PSMA PET imaging resulted in major and/or minor changes to RT plans in 24 patients (53%).

    68Ga-PSMA-11 PET imaging resulted in RT changes in 53% of patients. Prospective investigation is needed to evaluate the clinical benefit of RT changes based on staging 68Ga-PSMA-11 PET imaging.

  5. #85
    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.

    Materials and methods
    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.
    Last edited by DjinTonic; 01-07-2019 at 03:36 PM.

  6. #86
    Long-term results of a phase II study of hypofractionated proton therapy for prostate cancer: moderate versus extreme hypofractionation
    [2019, Full Text]



    We performed a prospective phase II study to compare acute toxicity among five different hypofractionated schedules using proton therapy. This study was an exploratory analysis to investigate the secondary end-point of biochemical failure-free survival (BCFFS) of patients with long-term follow-up.

    Eighty-two patients with T1-3bN0M0 prostate cancer who had not received androgen-deprivation therapy were randomized to one of five arms: Arm 1, 60 cobalt gray equivalent (CGE)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; and Arm 5, 35 CGE/5 fractions/4 weeks. In the current exploratory analysis, these ardms were categorized into the moderate hypofractionated (MHF) group (52 patients in Arms 1–3) and the extreme hypofractionated (EHF) group (30 patients in Arms 4–5).

    At a median follow-up of 7.5 years (range, 1.3–9.6 years), 7-year BCFFS was 76.2% for the MHF group and 46.2% for the EHF group (p = 0.005). The 7-year BCFFS of the MHF and EHF groups were 90.5 and 57.1% in the low-risk group (p = 0.154); 83.5 and 42.9% in the intermediate risk group (p = 0.018 ); and 41.7 and 40.0% in the high risk group (p = 0.786), respectively. Biochemical failure tended to be a late event with a median time to occurrence of 5 years. Acute GU toxicities were more common in the MHF than the EHF group (85 vs. 57%, p = 0.009), but late GI and GU toxicities did not differ between groups.

    Our results suggest that the efficacy of EHF is potentially inferior to that of MHF and that further studies are warranted, therefore, to confirm these findings.

    Trial registration
    This study is registered at ClinicalTrials.gov, no. NCT01709253; registered October 18, 2012; retrospectively registered).

  7. #87
    A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer



    External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS.

    Using the National Cancer Database, we identified 122,896 patients who were diagnosed with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer between 2004 and 2014 and treated with DE-EBRT (75.6–86.4 Gy), LDR boost, or HDR boost. We compared the OS among the three groups using multivariable Cox proportional hazards regression. Inverse probability treatment weighting was used to adjust for covariate imbalance.

    On multivariable Cox proportional hazards regression, HDR boost was associated with a similar OS to LDR boost (adjusted hazard ratio [AHR] 1.03 [0.96, 1.11]; p = 0.38 ) but significantly better OS than DE-EBRT (AHR 1.36 [1.29, 1.44]; p < 0.001). Inverse probability treatment weighting analysis yielded similar results. There was no significant difference between LDR and HDR boosts for National Comprehensive Cancer Network intermediate-risk (AHR 1.05 [0.96, 1.15]; p = 0.32) and high-risk (AHR 1.00 [0.89, 1.12]; p = 0.98 ) subgroups (p-interaction = 0.55).

    Our results suggest that HDR brachytherapy boost yields similar OS benefits compared with LDR brachytherapy boost for unfavorable-risk prostate cancer. HDR boost may be a suitable alternative to LDR boost.

  8. #88
    That's valuable to know, especially as there are fewer LDR specialists than than there were 15 years ago.

    I have read that there are trials underway to use SBRT as the boost therapy. That will also be important, as many of the newer RT devices can perform both EBRT and SBRT, making that boost treatment more widely available.
    DOB: May 1944
    In Active Surveillance program at Johns Hopkins
    Five biopsies from 2009 to 2014. The third and fourth biopsies were positive with one core and three cores <5% and G 3+3. Fifth biopsy was negative.
    OncotypeDX: 86 percent chance of PCa remaining indolent
    August 2015: tests are stable; no MRI or biopsy this year for my AS program
    August 2016: MRI unchanged from 2/2014
    April 2018: PSA 4.4, Free PSA 26. No change from six years ago.

  9. #89
    Quote Originally Posted by ASAdvocate View Post
    That's valuable to know, especially as there are fewer LDR specialists than than there were 15 years ago.

    I have read that there are trials underway to use SBRT as the boost therapy. That will also be important, as many of the newer RT devices can perform both EBRT and SBRT, making that boost treatment more widely available.
    It seems we are in a zone of uncertainty as to the best treatment for PCa men in a given situation. However, I think that is always the case -- technology moves fast, but intermediate- and long-term results obviously take time. In addition, the rise of good and promising advances increases the number of combinations, further complicating the picture. See also the article I posted in the main Forum about the split among ROs as to the best post-op RT strategy for high-risk men.
    Last edited by DjinTonic; 01-15-2019 at 03:00 PM.

  10. #90
    Time to PSA Nadir and the Risk of Death from Prostate Cancer following Radiation and Androgen Deprivation Therapy



    To assess whether the time to PSA nadir (TTN) has differential prognostic value in men who reach an undetectable versus detectable PSA nadir.

    Two-hundred and four men from a prospective randomized controlled trial (RCT) involving radiation therapy with or without 6 months of androgen deprivation therapy (ADT) in unfavorable risk CaP at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality (PCSM) calculated using Fine and Gray competing risk regression.

    After a median follow-up of 18.17 years, 160 men died; 30 (18.75%) of CaP. Amongst men with a PSA nadir ≥ 0.2 ng/ml, a TTN < median (12 months) was significantly associated with an increased PCSM-risk versus the median or more (AHR 5.07, 95%CI 2.10-12.23, p<0.001); whereas this association was not observed among men with a PSA nadir of <0.2 ng/ml, (AHR 9.9, 95%CI 0.23-433.8, p=0.23).

    Men with both a short TTN and detectable PSA nadir could be considered for entry on RCTs at a novel entry point prior to PSA failure at the time of PSA nadir to complete planned conventional ADT versus that plus agent(s) shown to improve outcomes in men with or at high risk of having castrate-resistant CaP.


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