Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer

Michalski, Jeff M.; Moughan, Jennifer; Purdy, James A.; Bosch, Walter; Bruner, Deborah Watkins; Bahary, Jean-Paul; Lau, Harold; Duclos, Marie; Parliament, Matthew; Morton, Gerard; Hamstra, Daniel A.; Seider, Michael J.; Lock, Michael; Patel, Malti; Vigneault, Éric; Winter, Kathryn; Sandler, Howard M.

doi:10.1001/jamaoncol.2018.0039

Cited by 259 publications

(190 citation statements)

References 23 publications

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“…This cohort comprised a sizable number of D'Amico highrisk patients (61.9%) and the majority were treated with IMRT (86.4%). Although dose escalation to between 74-80 Gy has been shown to improve FFBF in multiple previous trials (17)(18)(19)(20), particularly in patients with intermediate-to high-risk disease (9,21,22), our results suggest that there was no significant reduction in biochemical recurrence or survival benefit seen at 5 years. The reason for this apparent difference may be two-fold.…”

Section: Discussioncontrasting

confidence: 66%

“…Longterm results from several large randomised trials have demonstrated that ADT reduced biochemical failure and improved OS in patients with intermediate to high-risk disease (23)(24)(25)(26). However, ADT use was typically excluded in the aforementioned dose-escalation trials (17,18,21,22), accounted for only a small proportion of the cohort (19), or was limited to a short duration (neoadjuvant and concurrent) (20). In our study, 87.3% of the patients received ADT and 79.6% were treated for more than 6 months in duration.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience

Meng

Lim

Lee

et al. 2020

In Vivo

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Background/Aim: To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. Patients and Methods: Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. Results: A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate-and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). Conclusion: Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience

Meng

Lim

Lee

et al. 2020

In Vivo

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“…The NCTN/NCORP data set is a convenience sample of clinical trial data submitted to the NCTN from studies published after 2015. For all tumor types (except pancreas), publications from 21 clinical trials reported to NCTN/NCORP were reviewed for race/ethnic status (Table ).…”

Section: Methodsmentioning

confidence: 99%

Inclusiveness and ethical considerations for observational, translational, and clinical cancer health disparity research

Behring

Hale

Ozaydin

et al. 2019

Cancer

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Background Although general trends in cancer outcomes are improving, racial/ethnic disparities in patient outcomes continue to widen, suggesting disparity‐related shortcomings in cancer research designs. Methods Using convenience sampling, a total of 24 data sources, representing several research designs and 5 high‐burden tumor types, were included for analyses. The percentages of races/ethnicities across each design/tumor type were compared with those of the 2017 US Census data. The authors used a framework based on the Belmont principles to evaluate the ethical strengths and/or weaknesses of each design. Results In all designs, white individuals were found to be overrepresented. African American and Asian individuals were underrepresented, and Native Americans had consistently poor or no representation. In general, ethical concerns varied according to the study design. Clinical trials were high with regard to respect for persons and beneficence but low for equitable subject selection related to the inclusion of race/ethnicity. Observational study designs were more inclusive for race/ethnicity compared with clinical and translational studies, but their clinical usefulness was less. Conclusions The authors proposed that ethical concerns should vary according to the study design. Because observational designs have strengths in inclusiveness for race/ethnicity, their clinical usefulness can be improved by extending the Learning Health System in hospital catchment populations, the use of health records linked to biospecimens, and minority oversampling. Likewise, minority enrollment into clinical trials can be improved through Learning Health System linking and by using National Cancer Institute–mandated Community Outreach and Engagement Cores. This will allow precision medicine for otherwise overlooked minority subgroups.

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“…For patients with high-risk prostate cancer, treatment options most often include surgery or a combination of androgen deprivation therapy (ADT) and radiation therapy. External beam radiation therapy (EBRT) is the most common method to deliver radiotherapy for localized prostate cancer.Multiple studies have demonstrated that dose-escalated external beam radiation therapy (DE-EBRT) improves local control, freedom from biochemical failure, freedom from distance metastases, and decreases the need for salvage therapy (3)(4)(5)(6). DE-EBRT, however, has also been associated with increases in late genitourinary (GU) and gastrointestinal (GI) toxicities (3).…”

Section: Introductionmentioning

confidence: 99%

“…External beam radiation therapy (EBRT) is the most common method to deliver radiotherapy for localized prostate cancer.Multiple studies have demonstrated that dose-escalated external beam radiation therapy (DE-EBRT) improves local control, freedom from biochemical failure, freedom from distance metastases, and decreases the need for salvage therapy (3)(4)(5)(6). DE-EBRT, however, has also been associated with increases in late genitourinary (GU) and gastrointestinal (GI) toxicities (3). In the NRG Oncology/RTOG 0126 randomized clinical trial, the 5-years rates of both GI and GU late toxicity were increased with dose escalation (3).…”

Section: Introductionmentioning

confidence: 99%

A Brief Review of Low-Dose Rate (LDR) and High-Dose Rate (HDR) Brachytherapy Boost for High-Risk Prostate

et al. 2019

Self Cite

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For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities.

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Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer

Abstract: clinicaltrials.gov Identifier: NCT00033631.

Cited by 259 publications

References 23 publications

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience

Inclusiveness and ethical considerations for observational, translational, and clinical cancer health disparity research

A Brief Review of Low-Dose Rate (LDR) and High-Dose Rate (HDR) Brachytherapy Boost for High-Risk Prostate

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