Delivery of Radiation at the Lowest Dose Rate by a Modern Linear Accelerator is Most Effective in Inhibiting Prostate Cancer Growth

Purpose: External beam radiotherapy is one of the treatment options for organ-confined prostate cancer. A total dose of 70 to 81 Gray (Gy) is given daily (1.8-2.5 Gy/d), with a dose rate of 3 to 6 Gy/min over 28 to 45 treatments during 8 to 9 weeks. We applied the latest technological development in linear accelerators for enabling a wide range of dose rates (from 0.2-21 Gy/min) to test the effect of different delivery dose rates on prostate tumor growth in an animal xenograft model. Materials and Methods: A prostate cancer xenograft model was established in CD1/nude mice by means of PC-3 and CL-1 cells. The animals were radiated by a TrueBeam linear accelerator that delivered 4 dose rates ranging from 0.6 to 14 Gy/min, and reaching a total dose of 20 Gy. The mice were weighed and monitored for tumor development twice weekly. A 2-way analysis of variance was used to compare statistical differences between the groups. Results: Tumor growth was inhibited by radiation at all 4 dose rates in the 20 study mice compared to no radiation (n = 5, controls). The most significant reduction in tumor volumes was observed when the same dose of radiation was delivered at a rate of 0.6 Gy/min ( P < .01). The animals’ weights were not affected by any dose rate. Conclusions: Delivery of radiation with a TrueBeam linear accelerator at the lowest possible rate was most effective in prostate cancer growth inhibition and might be considered a preferential treatment mode for localized prostate cancer.

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LOW-DOSE-RATE OR HIGH-DOSE-RATE BRACHYTHERAPY IN COMBINATION WITH EXTERNAL BEAM RADIOTHERAPY FOR INTERMEDIATE AND HIGH-RISK PROSTATE CANCER

Problems in oncology ◽

10.37469/0507-3758-2018-64-1-79-83 ◽

2018 ◽

Vol 64 (1) ◽

pp. 79-83

Author(s):

Vladimir Solodkiy ◽

Andrey Pavlov ◽

Aleksey Tsybulskiy ◽

Anton Ivashin

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Dose Rate ◽

Low Dose ◽

External Beam Radiotherapy ◽

Combined Treatment ◽

High Dose ◽

External Beam ◽

Low Dose Rate ◽

Risk Of Progression

Introduction. One of the main problems of modem on-courology is treatment for prostate cancer of intermediate and high risk of progression. Modern radiotherapy in this category of patients has an advantage over surgical methods of treatment. One way to improve the effectiveness of radiotherapy is to escalate the dose in the prostate gland. For this purpose a combination of brachytherapy and remote radiotherapy is used. This combination allows increasing the dose of radiation, thereby providing better local control, reducing complications from neighboring organs. Purpose of the study. To conduct a comparative analysis of efficacy and safety of radical treatment of patients with prostate cancer at medium and high risk of progression using a combination of high and low dose rate brachytherapy with external beam radiotherapy. Materials and methods. 107 patients with prostate cancer of the group of medium and high risk of progression combined treatment (brachytherapy with external beam radiotherapy) was conducted. 53 patients underwent combined treatment (HDR-brachytherapy and external beam radiotherapy). 54 patients underwent combined treatment (LDR-brachytherapy and external beam radiotherapy). The observation period was 5 years. Conclusion. In a comparative analysis in groups of combined radiotherapy with the use of high-dose and low-dose-rate brachytherapy, the same effectiveness of immediate and long-term results of treatment was demonstrated. A significant reduction in early and late toxic reactions in patients with high-power brachytherapy has been demonstrated.

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Influence of isotope selection on morbidity of external beam radiotherapy with low-dose-rate boost for prostate cancer

Brachytherapy ◽

10.1016/j.brachy.2009.03.175 ◽

2009 ◽

Vol 8 (2) ◽

pp. 175-176

Author(s):

Junzo P. Chino ◽

Mitchell S. Anscher ◽

Carol A. Hahn ◽

W. Robert Lee ◽

Bridget F. Koontz

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

Low Dose ◽

External Beam Radiotherapy ◽

External Beam ◽

Low Dose Rate

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High-Dose-Rate Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Clinical Predictive Factor for Biochemical Relapse-Free Survival

Brachytherapy ◽

10.1016/j.brachy.2011.02.186 ◽

2011 ◽

Vol 10 ◽

pp. S93

Author(s):

Shinji Kariya ◽

Ichiro Yamasaki ◽

Kenji Tamura ◽

Taro Shuin ◽

Akihito Nishioka ◽

...

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

Predictive Factor ◽

External Beam Radiotherapy ◽

High Dose Rate ◽

High Dose ◽

External Beam ◽

Biochemical Relapse ◽

Relapse Free Survival ◽

Free Survival

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Selenite Treatment Inhibits LAPC-4 Tumor Growth and Prostate-Specific Antigen Secretion in a Xenograft Model of Human Prostate Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2008.07.005 ◽

2008 ◽

Vol 72 (3) ◽

pp. 935-940 ◽

Cited By ~ 15

Author(s):

Rumi S. Bhattacharyya ◽

Bryan Husbeck ◽

David Feldman ◽

Susan J. Knox

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Xenograft Model ◽

Human Prostate ◽

Human Prostate Cancer

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High-dose-rate brachytherapy monotherapy versus low-dose-rate brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

Radiotherapy and Oncology ◽

10.1016/j.radonc.2018.10.020 ◽

2019 ◽

Vol 132 ◽

pp. 162-170 ◽

Cited By ~ 7

Author(s):

Hideya Yamazaki ◽

Koji Masui ◽

Gen Suzuki ◽

Satoaki Nakamura ◽

Kei Yamada ◽

...

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

Low Dose ◽

External Beam Radiotherapy ◽

High Dose Rate ◽

Localized Prostate Cancer ◽

High Dose ◽

External Beam ◽

Low Dose Rate ◽

Low Dose Rate Brachytherapy

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Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.764536 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jörg Tamihardja ◽

Paul Lutyj ◽

Johannes Kraft ◽

Dominik Lisowski ◽

Stefan Weick ◽

...

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

External Beam Radiotherapy ◽

High Dose Rate ◽

Localized Prostate Cancer ◽

High Dose ◽

High Dose Rate Brachytherapy ◽

Brachytherapy Boost ◽

Gi Toxicity

PurposeEvaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer.Methods338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition.ResultsMedian follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%.ConclusionsTwo-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.

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What pelvic radiation disease symptoms are experienced by patients receiving external beam radiotherapy and a high-dose-rate brachytherapy boost for prostate cancer?

Journal of Contemporary Brachytherapy ◽

10.5114/jcb.2017.70731 ◽

2017 ◽

Vol 5 ◽

pp. 393-402 ◽

Cited By ~ 2

Author(s):

Georgia K.B. Halkett ◽

Michala Short ◽

Samar Aoun ◽

David Joseph ◽

Sean Bydder ◽

...

Keyword(s):

Prostate Cancer ◽

Dose Rate ◽

External Beam Radiotherapy ◽

High Dose Rate ◽

High Dose ◽

External Beam ◽

High Dose Rate Brachytherapy ◽

Disease Symptoms ◽

Pelvic Radiation ◽

Brachytherapy Boost

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An Anti-PSMA Immunotoxin Reduces Mcl-1 and Bcl2A1 and Specifically Induces in Combination with the BAD-Like BH3 Mimetic ABT-737 Apoptosis in Prostate Cancer Cells

Cancers ◽

10.3390/cancers12061648 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1648

Author(s):

Anie P. Masilamani ◽

Viviane Dettmer-Monaco ◽

Gianni Monaco ◽

Toni Cathomen ◽

Irina Kuckuck ◽

...

Keyword(s):

Prostate Cancer ◽

Combination Therapy ◽

Tumor Growth ◽

Cancer Cells ◽

Xenograft Model ◽

Target Cells ◽

Prostate Cancer Cells ◽

Mouse Xenograft Model ◽

Synergistic Cytotoxicity ◽

3D Spheroids

Background: Upregulation of anti-apoptotic Bcl-2 proteins in advanced prostate cancer leads to therapeutic resistance by prevention of cell death. New therapeutic approaches aim to target the Bcl-2 proteins for the restoration of apoptosis. Methods: The immunotoxin hD7-1(VL-VH)-PE40 specifically binds to the prostate specific membrane antigen (PSMA) on prostate cancer cells and inhibits protein biosynthesis. It was tested with respect to its effects on the expression of anti-apoptotic Bcl-2 proteins. Combination with the BAD-like mimetic ABT-737 was examined on prostate cancer cells and 3D spheroids and in view of tumor growth and survival in the prostate cancer SCID mouse xenograft model. Results: The immunotoxin led to a specific inhibition of Mcl-1 and Bcl2A1 expression in PSMA expressing target cells. Its combination with ABT-737, which inhibits Bcl-2, Bcl-xl, and Bcl-w, led to an induction of the intrinsic apoptotic pathway and to a synergistic cytotoxicity in prostate cancer cells and 3D spheroids. Furthermore, combination therapy led to a significantly prolonged survival of mice bearing prostate cancer xenografts based on an inhibition of tumor growth. Conclusion: The combination therapy of anti-PSMA immunotoxin plus ABT-737 represents the first tumor-specific therapeutic approach on the level of Bcl-2 proteins for the induction of apoptosis in prostate cancer.

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