High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: results of a phase II trial

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.

Download Full-text

Effects of low dose radiation on immune cells subsets and cytokines in mice

Toxicology Research ◽

10.1093/toxres/tfaa017 ◽

2020 ◽

Vol 9 (3) ◽

pp. 249-262

Author(s):

Xiaochang Liu ◽

Zheng Liu ◽

Duo Wang ◽

Yang Han ◽

Sai Hu ◽

...

Keyword(s):

Immune System ◽

Immune Cells ◽

Low Dose ◽

White Blood Cells ◽

Whole Body ◽

Low Dose Radiation ◽

Dose Irradiation ◽

Significant Difference ◽

Dose Radiation

Abstract Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.

Download Full-text

The Effects of Low Dose Radiation and High-dose-rate Radiation with Amifostine in a Large-scale Mouse Study

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2009.07.1273 ◽

2009 ◽

Vol 75 (3) ◽

pp. S557

Author(s):

M. Alcantara ◽

D. Paunesku ◽

T. Paunesku ◽

A. Wahl ◽

Y. Kataoka ◽

...

Keyword(s):

Dose Rate ◽

Large Scale ◽

Low Dose ◽

High Dose Rate ◽

High Dose ◽

Low Dose Radiation ◽

Mouse Study ◽

Dose Radiation

Download Full-text

Long-term Follow-up of ECOG E4292: A Phase II Trial of High Dose Radiation with Concurrent 5-Fluorouracil and Cisplatin in Patients with Anal Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2009.07.085 ◽

2009 ◽

Vol 75 (3) ◽

pp. S27

Author(s):

A. Chakravarthy ◽

P.J. Catalano ◽

J.A. Martenson ◽

J.K. Mondschein ◽

H. Wagner ◽

...

Keyword(s):

Phase Ii ◽

Anal Cancer ◽

Phase Ii Trial ◽

High Dose ◽

Long Term Follow Up ◽

Dose Radiation

Download Full-text

Should We Discount Low Dose Radiation Risk?

9th ASME International Conference on Radioactive Waste Management and Environmental Remediation: Volumes 1, 2, and 3 ◽

10.1115/icem2003-4829 ◽

2003 ◽

Author(s):

Richard Peckover ◽

Nick Priest

Keyword(s):

Precautionary Principle ◽

Low Dose ◽

Radiation Risk ◽

Low Dose Radiation ◽

Natural Radiation ◽

Dose Irradiation ◽

Current Concern ◽

The Relationship ◽

Dose Radiation

This paper addresses four inter-related topics of current concern: (i) the relationship between man-made and natural radiation; (ii) the uncertainties in predicted consequences following low dose irradiation; (iii) the scope for using a Properly Prioritized Precautionary Principle (P4); and (iv) why unobservable effects should not be a cause of concern.

Download Full-text

ACTR-07. LONG-TERM OUTCOMES FROM INTERGROUP NCCTG 86-72-51 (ALLIANCE): FINAL REPORT OF A PHASE III PROSPECTIVE RANDOMIZED TRIAL OF HIGH DOSE VERSUS LOW DOSE RADIATION IN ADULT SUPRATENTORIAL LOW-GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.051 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi13-vi14

Author(s):

William Breen ◽

S Keith Anderson ◽

Xiomara Carrero ◽

Paul Brown ◽

Karla Ballman ◽

...

Keyword(s):

Low Dose ◽

Low Grade Glioma ◽

Phase Iii ◽

High Dose ◽

Low Grade ◽

Tumor Diameter ◽

Low Dose Radiation ◽

Dose Radiation

Abstract PURPOSE To provide a final update on oncologic and cognitive outcomes of high dose versus low dose radiation for low-grade glioma. METHODS Between 1986 and 1994, 203 patients with supratentorial low grade glioma were randomized to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Histologic subtype was oligodendroglioma (71%) or astrocytoma (29%). Primary outcome was overall survival (OS). Cognitive status was followed using Folstein Mini-Mental State Examination (MMSE). RESULTS For the entire cohort of 203 patients, median OS was 8.4 years (95% CI: 7.2 – 10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3 – 6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve OS (15-yr OS: 22.4% vs. 24.9%, log rank p=0.978) or PFS (15-yr PFS: 15.2% vs. 9.5%, p=0.7142). OS was significantly better for patients with pre-operative tumor diameter < 5 cm (15-yr OS: 39.4% vs. 15.2%, p< 0.001), baseline MMSE > 27 (15-yr OS: 27.3% vs. 9.8%, p=0.001), and for patients who underwent gross total resection (GTR) (15-yr OS: 39.3% GTR vs. 16.4% subtotal resection vs. 24.5% biopsy only, p=0.0119). PFS was improved for patients with oligodendroglioma versus astrocytoma (15-yr PFS: 13.8% vs. 8.6%, p=0.0221). PFS was also improved for patients with pre-operative tumor diameter < 5 cm, patients who had GTR, and patients with baseline MMSE > 27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. CONCLUSIONS Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Minimal late decline in cognitive function after radiation was seen by MMSE. SUPPORT: U10CA180821,U10CA180882. https://acknowledgments.alliancefound.org

Download Full-text

Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer: A randomized phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.266 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 266-266 ◽

Cited By ~ 1

Author(s):

H. Khaled ◽

F. Abu-Taleb ◽

R. Haggag ◽

A. Zekri

Keyword(s):

Bladder Cancer ◽

Disease Progression ◽

Phase Ii ◽

Low Dose ◽

Response Rate ◽

Phase Ii Trial ◽

High Dose ◽

Prolonged Infusion ◽

Significant Difference ◽

Gemcitabine And Cisplatin

266 Background: Bladder carcinoma is the foremost oncologic problem in Egypt. Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer based on a previously published phase II trial. Methods: To compare efficacy and safety of both prolonged infusion and standard gemcitabine-cisplatin combination, this phase II randomized study of 60 untreated patients with stage III/IV bladder cancer was conducted. Patients were randomized to receive either gemcitabine (250 mg/m2) 6-hour infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm1) or gemcitabine (1,250 mg/m2) 30-min infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm 2). Results: The 47 males and 13 females had a median age of 60 years (range 40-73 years). A total of 44 patients had transitional cell, 12 had squamous cell, and 4 had undifferentiated cell carcinoma. Among the 53 evaluable patients (26 patients in arm1 and 27 patients in arm 2), complete response rate was achieved in 19.3% (5/26 patients of arm 1) and 7.4% (2/27 patients of arm 2). Eight patients in arm 1 (30.7%) and 7 patients (25.9%) in arm 2 had partial response on therapy. Thus the overall response rate of patients in arm1 and arm 2 was 50% (13/26 patients) and 33.3% (9/27patients), respectively (p = 0.21). No significant difference in median time to disease progression (6.7 months versus 7.9 months, p = 0.42), median survival (9.7 months versus 8.8 months, p = 0.3), and 1-year survival (27% versus 6%, p = 0.3) was detected between arms 1 and 2, respectively. No treatment- related deaths occurred. Main hematologic and nonhematologic toxicities were similar in both arms with no statistically significant differences. Conclusions: In the treatment of advanced bilharzial bladder cancer, gemcitabine in low dose and prolonged infusion in combination with cisplatin is not inferior to high-dose short infusion gemcitabine and cisplatin in terms of overall survival, time to disease progression, and response rates with favorable toxicity profile and less financial costs. No significant financial relationships to disclose.

Download Full-text