Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

doi:10.3390/cancers14122946

. 2022 Jun 15;14(12):2946.

doi: 10.3390/cancers14122946.

Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

Tugce Kutuk¹, Ranjini Tolakanahalli^{1

2}, Nicole C McAllister¹, Matthew D Hall^{1

2}, Martin C Tom^{1

2}, Muni Rubens³, Haley Appel¹, Alonso N Gutierrez^{1

2}, Yazmin Odia⁴, Alexander Mohler⁴, Manmeet S Ahluwalia⁵, Minesh P Mehta^{1

2}, Rupesh Kotecha^{1

2

6}

Affiliations

¹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
² Department of Radiation Oncology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
³ Department of Clinical Informatics, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁴ Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁵ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁶ Department of Translational Oncology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.

PMID: 35740612
PMCID: PMC9221236
DOI: 10.3390/cancers14122946

Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

Tugce Kutuk et al. Cancers (Basel). 2022.

. 2022 Jun 15;14(12):2946.

doi: 10.3390/cancers14122946.

Authors

Affiliations

¹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
² Department of Radiation Oncology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
³ Department of Clinical Informatics, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁴ Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁵ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁶ Department of Translational Oncology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.

PMID: 35740612
PMCID: PMC9221236
DOI: 10.3390/cancers14122946

Abstract

Purpose: The objective was to describe PRDR outcomes and report EQD2 OAR toxicity thresholds.

Methods: Eighteen patients with recurrent primary CNS tumors treated with PRDR at a single institution between April 2017 and September 2021 were evaluated. The radiotherapy details, cumulative OAR doses, progression-free survival (PFS), overall survival (OS), and toxicities were collected.

Results: The median PRDR dose was 45 Gy (range: 36-59.4 Gy); the median cumulative EQD2 prescription dose was 102.7 Gy (range: 93.8-120.4 Gy). The median cumulative EQD2 D_0.03cc for the brain was 111.4 Gy (range: 82.4-175.2 Gy). Symptomatic radiation necrosis occurred in three patients, for which the median EQD2 brain D_0.03cc was 115.9 Gy (110.4-156.7 Gy). The median PFS and OS after PRDR were 6.3 months (95%CI: 0.9-11.6 months) and 8.6 months (95%CI: 4.9-12.3 months), respectively. The systematic review identified five peer-reviewed studies with a median cumulative EQD2 prescription dose of 110.3 Gy. At a median follow-up of 8.7 months, the median PFS and OS were 5.7 months (95%CI: 2.1-15.4 months) and 6.7 months (95%CI: 3.2-14.2 months), respectively.

Conclusion: PRDR re-irradiation is a relatively safe and feasible treatment for recurrent primary CNS tumors. Despite high cumulative dose to OARs, the risk of high-grade, treatment-related toxicity within the first year of follow-up remains acceptable.

Keywords: CNS malignancies; PRDR; glioma; pulsed reduced dose rate radiotherapy; re-irradiation; recurrence.

PubMed Disclaimer

Conflict of interest statement

M.D.H.: Proton Collaborative Group Executive Committee Institutional Representative and Voting Member, Miami Cancer Institute (unpaid). Grant Funding: Live Like Bella Pediatric Cancer Research Initiative, Florida Department of Health Grants 8LA04 and 22L01, M.C.T.: Honoraria from ViewRay. Institutional research funding from Blue Earth Diagnostics Ltd. Personal fees from Elsevier. H.A.: Honoraria from Novocure Inc. A.N.G.: Honoraria from ViewRay, Inc., Elekta AB, IBA Y.O.: Trial support (BMS, Novocure), DSMC (GammaTile, Actuate, Oncoceutics/Chimerix), Advisory Board (Novocure, Abbvie), and Consulting (Abbvie). M.S.A.: Receipt of grants/research supports: Astrazeneca, Abbvie, BMS, Bayer, Incyte, Pharmacyclics, Novocure, Merck. Stock shareholder: Doctible, Mimivax. Receipt of honoraria or consultation fees: Elsevier, Wiley, Abvvie, VBI Vaccines, Bayer, karyopharm, Tocagen, Forma therapeutics M.P.M.: Consulting Fees from Karyopharm, Sapience, Zap, Mevion, Xoft; BOD Oncoceutics; Stock in Chimerix. R.K.: Honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., and Brainlab and institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay Inc., and Brainlab.

Figures

**Figure 1**
Institutional workflow demonstrating the calculation of EQD2 dose summation using prior dose and PRDR dose distributions.

**Figure 2**
Schematic diagram illustrating the delivery of a PRDR treatment fraction using fixed-field IMRT technique. The diagram depicts the temporal sequence of individual field delivery during the treatment fraction.

See this image and copyright information in PMC

Cited by

Initial feasibility cohort of temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade intracranial malignancies.
La Rosa A, Fellows Z, Wroe AJ, Coutinho L, Pons E, McAllister NC, Tolakanahalli R, Kutuk T, Hall MD, Press RH, McDermott MW, Odia Y, Ahluwalia MS, Mehta MP, Gutierrez AN, Kotecha R. La Rosa A, et al. Sci Rep. 2024 Nov 4;14(1):26685. doi: 10.1038/s41598-024-78370-x. Sci Rep. 2024. PMID: 39496803 Free PMC article.
Pulsed low-dose rate radiotherapy for recurrent bone sarcomas: case reports and brief review.
Wong RX, Master Z, Pang E, Yang V, Looi WS. Wong RX, et al. Radiat Oncol J. 2024 Mar;42(1):88-94. doi: 10.3857/roj.2023.00815. Epub 2024 Feb 13. Radiat Oncol J. 2024. PMID: 38549388 Free PMC article.
Temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade gliomas.
La Rosa A, Gutierrez AN, Odia Y, McDermott MW, Ahluwalia MS, Mehta MP, Kotecha R. La Rosa A, et al. Neurooncol Adv. 2023 Jun 15;5(1):vdad074. doi: 10.1093/noajnl/vdad074. eCollection 2023 Jan-Dec. Neurooncol Adv. 2023. PMID: 37358937 Free PMC article. No abstract available.

References

1. Nabors L.B., Portnow J., Ahluwalia M., Baehring J., Brem H., Brem S., Butowski N., Campian J.L., Clark S.W., Fabiano A.J., et al. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2020;18:1537–1570. doi: 10.6004/jnccn.2020.0052. - DOI - PubMed
1. Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J., Janzer R.C., Ludwin S.K., Allgeier A., Fisher B., Belanger K., et al. Effects of radiotherapy with con-comitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466. doi: 10.1016/S1470-2045(09)70025-7. - DOI - PubMed
1. Cairncross G., Wang M., Shaw E., Jenkins R., Brachman D., Buckner J., Fink K., Souhami L., Laperriere N., Curran W., et al. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402. J. Clin. Oncol. 2013;31:337–343. doi: 10.1200/JCO.2012.43.2674. - DOI - PMC - PubMed
1. Buckner J.C., Shaw E.G., Pugh S.L., Chakravarti A., Gilbert M.R., Barger G.R., Coons S., Ricci P., Bullard D., Brown P.D., et al. Radiation plus Procarbazine, CCNU, and Vin-cristine in Low-Grade Glioma. N. Engl. J. Med. 2016;374:1344–1355. doi: 10.1056/NEJMoa1500925. - DOI - PMC - PubMed
1. Wallner K.E., Galicich J.H., Krol G., Arbit E., Malkin M.G. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int. J. Radiat. Oncol. 1989;16:1405–1409. doi: 10.1016/0360-3016(89)90941-3. - DOI - PubMed

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
Medical
- ClinicalTrials.gov
Miscellaneous
- NCI CPTAC Assay Portal

[1] Nabors L.B., Portnow J., Ahluwalia M., Baehring J., Brem H., Brem S., Butowski N., Campian J.L., Clark S.W., Fabiano A.J., et al. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2020;18:1537–1570. doi: 10.6004/jnccn.2020.0052. - DOI - PubMed

[2] Nabors L.B., Portnow J., Ahluwalia M., Baehring J., Brem H., Brem S., Butowski N., Campian J.L., Clark S.W., Fabiano A.J., et al. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2020;18:1537–1570. doi: 10.6004/jnccn.2020.0052. - DOI - PubMed

[3] Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J., Janzer R.C., Ludwin S.K., Allgeier A., Fisher B., Belanger K., et al. Effects of radiotherapy with con-comitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466. doi: 10.1016/S1470-2045(09)70025-7. - DOI - PubMed

[4] Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J., Janzer R.C., Ludwin S.K., Allgeier A., Fisher B., Belanger K., et al. Effects of radiotherapy with con-comitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466. doi: 10.1016/S1470-2045(09)70025-7. - DOI - PubMed

[5] Cairncross G., Wang M., Shaw E., Jenkins R., Brachman D., Buckner J., Fink K., Souhami L., Laperriere N., Curran W., et al. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402. J. Clin. Oncol. 2013;31:337–343. doi: 10.1200/JCO.2012.43.2674. - DOI - PMC - PubMed

[6] Cairncross G., Wang M., Shaw E., Jenkins R., Brachman D., Buckner J., Fink K., Souhami L., Laperriere N., Curran W., et al. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402. J. Clin. Oncol. 2013;31:337–343. doi: 10.1200/JCO.2012.43.2674. - DOI - PMC - PubMed

[7] Buckner J.C., Shaw E.G., Pugh S.L., Chakravarti A., Gilbert M.R., Barger G.R., Coons S., Ricci P., Bullard D., Brown P.D., et al. Radiation plus Procarbazine, CCNU, and Vin-cristine in Low-Grade Glioma. N. Engl. J. Med. 2016;374:1344–1355. doi: 10.1056/NEJMoa1500925. - DOI - PMC - PubMed

[8] Buckner J.C., Shaw E.G., Pugh S.L., Chakravarti A., Gilbert M.R., Barger G.R., Coons S., Ricci P., Bullard D., Brown P.D., et al. Radiation plus Procarbazine, CCNU, and Vin-cristine in Low-Grade Glioma. N. Engl. J. Med. 2016;374:1344–1355. doi: 10.1056/NEJMoa1500925. - DOI - PMC - PubMed

[9] Wallner K.E., Galicich J.H., Krol G., Arbit E., Malkin M.G. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int. J. Radiat. Oncol. 1989;16:1405–1409. doi: 10.1016/0360-3016(89)90941-3. - DOI - PubMed

[10] Wallner K.E., Galicich J.H., Krol G., Arbit E., Malkin M.G. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int. J. Radiat. Oncol. 1989;16:1405–1409. doi: 10.1016/0360-3016(89)90941-3. - DOI - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

Affiliations

Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous