Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Acquisition
2.2. PRDR Re-Irradiation Technique
2.3. PRDR Treatment Planning and Delivery
2.4. Systematic Review of the Literature
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- De Robles, P.; Fiest, K.M.; Frolkis, A.D.; Pringsheim, T.; Atta, C.; St Germaine-Smith, C.; Day, L.; Lam, D.; Jette, N. The worldwide incidence and prevalence of primary brain tumors: A systematic review and meta-analysis. Neuro-Oncology 2015, 17, 776–783. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, X.; Liao, X.; Zhang, B.; He, H.; Shui, Y.; Xu, W.; Jiang, C.; Shen, L.; Wei, Q. Recurrence patterns in patients with high-grade glioma following te-mozolomide-based chemoradiotherapy. Mol. Clin. Oncol. 2016, 5, 289–294. [Google Scholar] [CrossRef] [Green Version]
- Shanker, M.; Chua, B.; Bettington, C.; Foote, M.C.; Pinkham, M.B. Re-irradiation for recurrent high-grade gliomas: A systematic review and analysis of treatment technique with respect to survival and risk of radionecrosis. Neuro-Oncol. Pract. 2019, 6, 144–155. [Google Scholar] [CrossRef]
- Amichetti, M.; Amelio, D. A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG). Cancers 2011, 3, 4061–4089. [Google Scholar] [CrossRef]
- Tsien, C.; Pugh, S.; Dicker, A.; Raizer, J.; Matuszak, M.; Lallana, E.; Huang, J.; Algan, O.; Taylor, N.; Portelance, L.; et al. ACTR-32. nrg oncology rtog 1205: Randomized phase II trial of concurrent bevacizumab and re-irradiation vs. bevacizumab alone as treatment for recurrent glioblastoma. Neuro-Oncology 2019, 21, vi20. [Google Scholar] [CrossRef]
- Adkison, J.B.; Tomé, W.; Seo, S.; Richards, G.M.; Robins, H.I.; Rassmussen, K.; Welsh, J.S.; Mahler, P.A.; Howard, S.P. Reirradiation of Large-Volume Recurrent Glioma with Pulsed Reduced-Dose-Rate Radiotherapy. Int. J. Radiat. Oncol. 2011, 79, 835–841. [Google Scholar] [CrossRef]
- Bovi, J.A.; Prah, M.A.; Retzlaff, A.A.; Schmainda, K.M.; Connelly, J.M.; Rand, S.D.; Marszalkowski, C.S.; Mueller, W.M.; Siker, M.L.; Schultz, C.J. Pulsed Reduced Dose Rate Radiotherapy in Conjunction with Bevacizumab or Bevacizumab Alone in Recurrent High-grade Glioma: Survival Outcomes. Int. J. Radiat. Oncol. 2020, 108, 979–986. [Google Scholar] [CrossRef] [PubMed]
- Magnuson, W.; Robins, H.I.; Mohindra, P.; Howard, S. Large volume reirradiation as salvage therapy for glioblastoma after progression on bevacizumab. J. Neuro-Oncol. 2014, 117, 133–139. [Google Scholar] [CrossRef] [PubMed]
- Mohindra, P.; Robins, H.I.; Tome, W.A.; Hayes, L.; Howard, S.P. Wide-field pulsed reduced dose rate radiotherapy (PRDR) for re-current ependymoma in pediatric and young adult patients. Anticancer Res. 2013, 33, 2611–2618. [Google Scholar] [PubMed]
- Murphy, E.S.; Rogacki, K.; Godley, A.; Qi, P.; Reddy, C.A.; Ahluwalia, M.S.; Peereboom, D.M.; Stevens, G.H.; Yu, J.S.; Kotecha, R.; et al. Intensity modulated radiation therapy with pulsed reduced dose rate as a reirradiation strategy for recurrent central nervous system tumors: An institutional series and literature review. Pract. Radiat. Oncol. 2017, 7, e391–e399. [Google Scholar] [CrossRef] [PubMed]
- Tome, W.A.; Howard, S.P. On the possible increase in local tumour control probability for gliomas exhibiting low dose hy-per-radiosensitivity using a pulsed schedule. Br. J. Radiol. 2007, 80, 32–37. [Google Scholar] [CrossRef]
- Short, S.C.; Kelly, J.; Mayes, C.R.; Woodcock, M.; Joiner, M.C. Low-dose hypersensitivity after fractionated low-dose irradiation in vitro. Int. J. Radiat. Biol. 2001, 77, 655–664. [Google Scholar]
- Joiner, M.C.; Marples, B.; Lambin, P.; Short, S.C.; Turesson, I. Low-dose hypersensitivity: Current status and possible mechanisms. Int. J. Radiat. Oncol. 2001, 49, 379–389. [Google Scholar] [CrossRef]
- Rong, Y.; Paliwal, B.; Howard, S.P.; Welsh, J. Treatment Planning for Pulsed Reduced Dose-Rate Radiotherapy in Helical Tomotherapy. Int. J. Radiat. Oncol. 2011, 79, 934–942. [Google Scholar] [CrossRef]
- Lin, M.H.; Price, R.A., Jr.; Li, J.; Kang, S.; Li, J.; Ma, C.M. Investigation of pulsed IMRT and VMAT for re-irradiation treatments: Do-simetric and delivery feasibilities. Phys. Med. Biol. 2013, 58, 8179–8196. [Google Scholar] [CrossRef]
- Cannon, G.M.; Tome, W.A.; Robins, H.I.; Howard, S.P. Pulsed reduced dose-rate radiotherapy: Case report: A novel re-treatment strategy in the management of recurrent glioblastoma multiforme. J. Neurooncol. 2007, 83, 307–311. [Google Scholar] [CrossRef] [PubMed]
- Fowler, J.F. The linear-quadratic formula and progress in fractionated radiotherapy. Br. J. Radiol. 1989, 62, 679–694. [Google Scholar] [CrossRef] [PubMed]
- Wobb, J.; Krueger, S.A.; Kane, J.L.; Galoforo, S.; Grills, I.S.; Wilson, G.D.; Marples, B. The Effects of Pulsed Radiation Therapy on Tumor Ox-ygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2015, 92, 820–828. [Google Scholar] [CrossRef] [PubMed]
- Meyer, K.; Krueger, S.A.; Kane, J.L.; Wilson, T.G.; Hanna, A.; Dabjan, M.; Hege, K.M.; Wilson, G.D.; Grills, I.; Marples, B. Pulsed Radiation Therapy with Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model. Int. J. Radiat. Oncol. 2016, 96, 161–169. [Google Scholar] [CrossRef] [PubMed]
- Richards, G.M.; Tomé, W.A.; Robins, H.I.; Stewart, J.A.; Welsh, J.S.; Mahler, P.A.; Howard, S.P. Pulsed reduced dose-rate radiotherapy: A novel locoregional retreatment strategy for breast cancer recurrence in the previously irradiated chest wall, axilla, or supraclavicular region. Breast Cancer Res. Treat. 2009, 114, 307–313. [Google Scholar] [CrossRef]
- Ma, C.-M.; Lin, M.H.; Dai, X.F.; Koren, S.; Klayton, T.; Wang, L.; Li, J.S.; Chen, L.; Price, R.A. Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques. Phys. Med. Biol. 2012, 57, 4613–4626. [Google Scholar] [CrossRef]
- Tyagi, N.; Yang, K.; Sandhu, R.; Yan, D.; Park, S.S.; Chen, P.Y.; Marples, B. External beam pulsed low dose radiotherapy using volumetric modulated arc therapy: Planning and delivery. Med. Phys. 2013, 40, 011704. [Google Scholar] [CrossRef]
- Ma, C.; Lin, M.; Wei, K.; Li, J.; Wang, P.; Lang, J. Pulsed Low-Dose-Rate Radiation Therapy (PLDR) for Recurrent Cancers: Treatment Planning Strategies for IMRT and VMAT. Int. J. Radiat. Oncol. 2014, 90, S941. [Google Scholar] [CrossRef]
- Lawrence, Y.R.; Li, X.A.; El Naqa, I.; Hahn, C.A.; Marks, L.B.; Merchant, T.E.; Dicker, A. Radiation Dose–Volume Effects in the Brain. Int. J. Radiat. Oncol. 2010, 76, S20–S27. [Google Scholar] [CrossRef] [Green Version]
- Mayer, R.; Sminia, P. Reirradiation Tolerance of the Human Brain. Int. J. Radiat. Oncol. 2008, 70, 1350–1360. [Google Scholar] [CrossRef]
- Sminia, P.; Mayer, R. External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain. Cancers 2012, 4, 379–399. [Google Scholar] [CrossRef] [PubMed]
- Minniti, G.; Niyazi, M.; Alongi, F.; Navarria, P.; Belka, C. Current status and recent advances in reirradiation of glioblastoma. Radiat. Oncol. 2021, 16, 36. [Google Scholar] [CrossRef] [PubMed]
- Witt, J.S.; Musunuru, H.B.; Bayliss, R.A.; Howard, S.P. Large volume re-irradiation for recurrent meningioma with pulsed reduced dose rate radiotherapy. J. Neuro-Oncol. 2019, 141, 103–109. [Google Scholar] [CrossRef] [PubMed]
- Burr, A.R.; Robins, H.I.; Bayliss, R.A.; Baschnagel, A.M.; Welsh, J.S.; Tomé, W.A.; Howard, S.P. Outcomes from Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy. Adv. Radiat. Oncol. 2020, 5, 834–839. [Google Scholar] [CrossRef]
- Burr, A.R.; Robins, H.I.; Bayliss, R.A.; Howard, S.P. Pulsed Reduced Dose Rate for Reirradiation of Recurrent Breast Cancer. Pract. Radiat. Oncol. 2020, 10, e61–e70. [Google Scholar] [CrossRef]
- Li, G.-H.; Zhu, B.; Yang, F.; Ma, C.-K.; Yang, D.-Q. Use of cetuximab in combination with pulsed reduced dose-rate radiotherapy in a patient with recurrence of nasopharyngeal carcinoma in the neck. Exp. Ther. Med. 2012, 3, 869–872. [Google Scholar] [CrossRef] [Green Version]
- Kazmi, F.; Soon, Y.Y.; Leong, Y.H.; Koh, W.Y.; Vellayappan, B. Re-irradiation for recurrent glioblastoma (GBM): A systematic review and meta-analysis. J. Neuro-Oncol. 2019, 142, 79–90. [Google Scholar] [CrossRef]
- Niranjan, A.; Iii, E.A.M.; Kano, H.; Flickinger, J.C.; Lunsford, L.D. Stereotactic Radiosurgery in the Multimodality Management of Residual or Recurrent Glioblastoma Multiforme. Prog. Neurol. Surg. 2018, 31, 48–61. [Google Scholar] [CrossRef]
- Clarke, J.; Neil, E.; Terziev, R.; Gutin, P.; Barani, I.; Kaley, T.; Lassman, A.B.; Chan, T.A.; Yamada, J.; DeAngelis, L.; et al. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy with Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int. J. Radiat. Oncol. 2017, 99, 797–804. [Google Scholar] [CrossRef]
- Saeed, A.M.; Khairnar, R.; Sharma, A.M.; Larson, G.L.; Tsai, H.K.; Wang, C.J.; Halasz, L.M.; Chinnaiyan, P.; Vargas, C.E.; Mishra, M.V. Clinical Outcomes in Patients with Recurrent Glio-blastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry. Adv. Radiat. Oncol. 2020, 5, 978–983. [Google Scholar] [CrossRef]
- Kotecha, R.; Tom, M.C.; Mehta, M.P. Novel Radiation Approaches. Neurosurg. Clin. N. Am. 2021, 32, 211–223. [Google Scholar] [CrossRef] [PubMed]
Median Age at PRDR | 37.5 Years (Range: 13–71 Years) |
---|---|
Gender | |
Female | 8 (44%) |
Male | 10 (56%) |
Tumor histology and grade at PRDR | |
Glioblastoma, IDH WT (WHO grade 4) | 9 (50%) |
Astrocytoma, IDH mutant (WHO grade 4) | 2 (11%) |
Astrocytoma, IDH WT (WHO grade 3) | 1(6%) |
Astrocytoma, IDH mutant (WHO grade 3) | 2 (11%) |
Oligodendroglioma, IDH mutant, 1p19q co-deleted (WHO grade 3) | 2 (11%) |
Pleomorphic xanthoastrocytoma, IDH WT (WHO grade 3) | 1 (6%) |
Astrocytoma, IDH mutant (WHO grade 2) | 1 (6%) |
Median number of surgeries before PRDR | 1.5 (range: 1–4) |
Median number of systemic therapy courses before PRDR | 2.5 (range:2–6) |
Median KPS at PRDR | 85 (range: 70–100) |
Median prescription dose of initial radiotherapy | 59.4 Gy (range: 50–75 Gy) |
Median time between initial radiotherapy and PRDR | 35.6 months (range: 7.0–122.0 months) |
Median prescription dose of PRDR | 45 Gy (range: 36–59.4 Gy) |
Median planning target volume of PRDR | 134.9 cc (range: 17.9–696.6 cc) |
Median cumulative prescription dose to target (EQD2) | 107.6 Gy (93.1–132.5 Gy) |
Variation | Dose Metric | Median Cumulative Dose [EQD2, α/β = 3], Gy (Range) |
---|---|---|
Brain | D0.03cc | 111.4 (82.4–175.2) |
D0.5cc | 109.9 (81.1–162.4) | |
D1cc | 108.8 (80.8–154.7) | |
Dmean | 35.1 (18.0–66.7) | |
Brainstem | D0.03cc | 85.4 (14.8–111.6) |
D0.5cc | 74.8 (12.2–104.4) | |
D1cc | 68.6 (11.2–101.9) | |
Dmean | 25 (3.9–94.4) | |
Optic chiasm | D0.03cc | 38.3 (10.4–96.8) |
Dmean | 32.8 (11.1–74.1) | |
Ipsilateral optic nerve | D0.03cc | 27.5 (3.5–100.6) |
Dmean | 16.2 (2.1–67.5) | |
Contralateral optic nerve | D0.03cc | 24.0 (3.2–66) |
Dmean | 12.2 (2.2–35.8) | |
Ipsilateral cochlea | Dmean | 30.8 (1.8–75.7) |
Contralateral cochlea | Dmean | 4.5 (0.5–66.8) |
Ipsilateral hippocampus | D0.03cc | 92.1 (67.1–118.8) |
Dmean | 60.6 (10.9–108.8) | |
Contralateral hippocampus | D0.03cc | 52.8 (3.2–112.6) |
Dmean | 37.8 (3.9–70.5) |
Variable | Grade 1 | Grade 2 | Grade 3 | Grade 4–5 |
---|---|---|---|---|
Headache | 8 (44%) | 3 (17%) | 0 | 0 |
Alopecia | 9 (50%) | 5 (28%) | 0 | 0 |
Seizure | 3 (17%) | 1 (6%) | 0 | 0 |
Dizziness | 6 (33%) | 0 | 0 | 0 |
Fatigue | 8 (44%) | 7 (39%) | 1 (6%) | 0 |
Nausea | 5 (28%) | 0 | 0 | 0 |
Cognitive disturbance | 2 (11%) | 1 (6%) | 0 | 0 |
Hearing impairment | 0 | 0 | 1 (6%) | 0 |
Blurred vision | 1 (6%) | 0 | 0 | 0 |
Dry eye | 1 (6%) | 0 | 0 | 0 |
Dysarthria | 0 | 1 (6%) | 0 | 0 |
Vertigo | 1 (6%) | 0 | 0 | 0 |
Total | 44 | 18 | 2 | 0 |
Study | Number of Patients | Diagnosis | Median Previous Radiotherapy Dose (Gy) | Median PRDR Re-irradiation Dose (Gy) | Cumulative Dose (Gy) | Median Target Volume (cm3) | Median Time from Previous Radiotherapy to PRDR (months) | Median PFS | Median OS | Side Effects |
---|---|---|---|---|---|---|---|---|---|---|
Adkison 2011 [11] | 103 | Low grade glioma: 25, Grade 3 glioma: 31, Grade 4 glioma: 45, Brainstem glioma: 1, Pineal tumor:1 | 59.4 (range: 50.4–72.5) | 50 (range: 22–58) | 106.8 | 369.2 (range: 89.6–1002.2) | 18.2 (range: 2–227.6) | NA | 5.8 months (range: 1–48.4 months) | 4 (3.9%) radiation necrosis |
Magnuson 2014 [13] | 23 | Grade 4 glioma | 60 (range: 59.4–60) | 54 | 114 | 424 (range: 74–776) | 11.8 (range: 6.8–36.8) | 3.7 months (range: 1.2–14.1 months) | 6.9 months (range: 2.7–12 months) | Zero grade 3+ toxicity |
Mohindra 2014 [14] | 5 | Ependymoma | 48.4 (range: 36–55.8) | 40 (range: 30.6–54) | 105.2 (range: 90–162.4) | Mean portal area of 348 cm2 | 58 months (range: 32–212 months) | 34 months (95% CI: 11–57 months) | 64 months (95% CI: 8–120 months) | Zero grade 3+ toxicity Zero radiation necrosis |
Murphy 2017 [15] | 24 | Grade 2: 4, Grade 3: 10, Grade 4: 8, NA: 2 | 59.7 (range: 38–60) | 54 (range: 38–60) | 113.7 (range: 97.4–120), 1 patient got PRDR twice: 169.2 Gy | Mean: 369.1 +/− 177.9 | 47.8 months (range: 11–389.1 months) | 3.1 months | 8.7 months | Total 20 (18.1%) side effects, Zero radiation necrosis |
Bovi 2020 [12] | 33 patients bevacizumab + PRDR | Grade 3: 14,Grade 4: 19 | NA | 50–54 | NA | NA | NA | 12 months (95% CI: 10–16 months) | 16 months (95% Cl: 15–21 months) | NA |
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Kutuk, T.; Tolakanahalli, R.; McAllister, N.C.; Hall, M.D.; Tom, M.C.; Rubens, M.; Appel, H.; Gutierrez, A.N.; Odia, Y.; Mohler, A.; et al. Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results. Cancers 2022, 14, 2946. https://doi.org/10.3390/cancers14122946
Kutuk T, Tolakanahalli R, McAllister NC, Hall MD, Tom MC, Rubens M, Appel H, Gutierrez AN, Odia Y, Mohler A, et al. Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results. Cancers. 2022; 14(12):2946. https://doi.org/10.3390/cancers14122946
Chicago/Turabian StyleKutuk, Tugce, Ranjini Tolakanahalli, Nicole C. McAllister, Matthew D. Hall, Martin C. Tom, Muni Rubens, Haley Appel, Alonso N. Gutierrez, Yazmin Odia, Alexander Mohler, and et al. 2022. "Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results" Cancers 14, no. 12: 2946. https://doi.org/10.3390/cancers14122946