Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection, Clinical Outcomes, and Adverse Events
2.2. Statistical Analysis
2.3. Imaging
3. Results
3.1. Baseline Characteristics
3.2. Treatment Disposition
3.3. Clinical Outcome
3.4. Objective Response on MRI of the Brain
3.5. Safety
3.6. Survival
4. Case Illustrations
4.1. Case Illustration 1
4.2. Case Illustration 2
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | No. of Patients (%) Total (n = 13) |
---|---|
Median age, years (range) | 52 (33–68) |
Sex | |
Male | 7 (54%) |
Female | 6 (46%) |
Primary disease | |
Melanoma | 6 (46%) |
Non-small cell lung carcinoma | 3 (23%) |
Breast cancer | 1 (8%) |
Renal cell carcinoma | 1 (8%) |
Medulloblastoma | 1 (8%) |
Arteriovenous malformation | 1 (8%) |
WHO-PS at inclusion | |
0 | 10 (77%) |
1 | 3 (23%) |
Number of fRNB locations | |
1 | 9 (69%) |
2 | 3 (23%) |
3 | 1 (8%) |
Prior radiation therapy | |
Stereotactic radiosurgery | 6 (46%) |
Stereotactic radiotherapy | 3 (23%) |
Both | 4 (31%) |
Corticosteroid treatment prior to initiation of bevacizumab | |
Yes | 5 (39%) |
No | 8 (62%) |
Diagnosis of fRNB based on MRI supported by | |
Histopathological examination of biopsy | 6 (46%) |
18F-FDG PET-CT | 6 (46%) |
MRI-only | 3 (23%) |
Symptoms at baseline | |
Headache | 1 (8%) |
Epileptic seizures | 6 (46%) |
Focal neurological deficit | 9 (69%) |
Patient | Primary Disease | Location of fRNB | Radiation Therapy | Prior ICI | Prior Chemotherapy | Time since SRS/SRT | WHO-PS Evolution | Time on Treatment | Re-challenge Needed | Steroids Prior | Symptomatic Improvement |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | NSCLC | Right frontal | SRS (1 × 20 Gy) | 23 | 1 -> 1 | 5 | N | Y1 | Y | ||
2 | MEL | Left parietal | SRS (1 × 20 Gy) | IPI + NIVO + PEMBRO | 43 | 0 -> 1 | 40 | Y | N | Y/N | |
3 | NSCLC | Bilateral parietal | SRS (20 Gy) | PEMBRO | 37 | 0 -> 1 | 5 | N | N | Y | |
4 | RCC | Right frontoparietal | SRS (20 Gy) + SRT (5 × 7.5 Gy) | NIVO | 58 | 0 -> 0 | 8 | N | N | Y | |
5 | MB | Left supratentorial | SRT (doses see case report 1) | Carboplatin + etoposide | 79 | 0 -> 0 | 11 | Y | N | Y | |
6 | AVM | Right parietal | SRS (1 × 20 Gy) | 79 | 0 -> 0 | 5 | N | N | Y | ||
7 | BC | Left temporal | SRS (1 × 20 Gy) + SRT (5 × 7 Gy) | Paclitaxel | 90 | 0 -> 0 | 3 | Y | N | Y | |
8 | MEL | Left frontoparietal | SRT+SRS (see case report 2) | IPI + NIVO | 18 | 1 -> 1 | 11 | Y | Y1 | Y | |
9 | MEL | Right frontal | SRS (1 × 20 Gy) | IPI + NIVO + PEMBRO | 60 | 0 -> 1 | 1 | N | Y1 | Y | |
10 | MEL | Bilateral frontoparietal | SRS (1 × 20 Gy) | IPI + NIVO | Temozolomide | 38 | 0 -> 0 | 4 | Y | N | Y |
11 | MEL | Left cerebellar | SRT (3 × 9 Gy) | 24 | 0 -> 0 | 10 | N | N | Y | ||
12 | MEL | Right cerebellum | SRT (4 × 8 Gy) | PEMBRO | 39 | 0 -> 0 | 20 | N | N | Y | |
13 | NSCLC | Right temporal | SRS (1 × 20 Gy) + SRT (5 × 7 Gy) | PEMBRO | Cisplatin + docetaxel | 32 | 1 -> 0 | 2 | N | Y | N |
All AE | n = 6 | |||
---|---|---|---|---|
Grade I | Grade II | Grade III | Grade IV | |
Arterial Hypertension (n [%]) | 2 (15%) | 0 | 0 | 0 |
Headache (n [%]) | 1 (8%) | 1 (8%) | 0 | 0 |
Alopecia (n [%]) | 2 (15%) | 0 | 0 | 0 |
Mucositis oral (n [%]) | 2 (15%) | 0 | 0 | 0 |
Diarrhea (n [%]) | 1 (8%) | 0 | 0 | 0 |
Epistaxis (n [%]) | 1 (8%) | 0 | 0 | 0 |
Proteinuria (n [%]) | 0 | 1 (8%) | 0 | 0 |
Wound dehiscence (n [%]) | 0 | 1 (8%) | 0 | 0 |
Citation | Study Design | No. of Patients | BEV Dose Regimen | Primary Pathologies (n) | Radiation (n) | Radiographic Response Rate (%) | Symptomatic Improvement (%) | Adverse Events Described (n) |
---|---|---|---|---|---|---|---|---|
Gonzalez et al., 2007. USA. [32] | Retrospective | 8 | 5 mg/kg q2w or 7.5 mg/kg q3w | AOA (1), AOD (1), AA (1), HP (1), GBM (4) | RT/SRS | 100% | None | |
Tye et al., 2014. USA. [29] | Review | 71 | 7.5 mg/kg q2w | GBM (22), Met (11), pG (15), Men (6), NPC (5), other (5), ponG (3), HP (2), AVM (2) | EBRT (57), SRS (9), BNCT (3), PT (2) | 100% | Small vessel thrombosis (3), sagittal sinus thrombosis (1), aspiration pneumonia (1), pneumonia with sepsis (1), pulmonary embolus (1) | |
Levin et al., 2012. USA. [33] | Randomized controlled trial | 7 | 7.5 mg q3w | NPC (2), MS (1), A (1), ODG (1), SCC (1), PA (1) | RT (7) | 100% | 100% | Small vessel thrombosis (3), aspiration pneumonia (1), pulmonary embolus secondary from a deep vein thrombosis (1), superior sagittal sinus thrombosis (1) |
Wang et al., 2012. China. [38] | Retrospective | 17 | 7.5 mg/kg q2w | GBM (7), Met (6), AA (1), AVM (1), Men (1), ODG (1) | EBRT (12), SRS (4), FSRT (2) | 100% | 94.1% | Hypertension (1), proteinuria (1), temporary fatigue (1) |
Boothe et al., 2013. USA [39]. | Retrospective | 11 | 7.5 mg/kg q2w or 10 mg/kg q3w or 15 mg/kg q6w | Met (11) | SRS (11), WBRT (5) | 100% | 63.6% | None |
Furuse et al., 2013. Japan. [40] | Retrospective | 11 | 5 mg/kg q2w | GBM (4), AM (3), Met (3), AA (1) | XRT (7), SRS (6), BNCT (3), SRT (1), | 100% | None | |
Yonezawa et al., 2014. Japan. [41] | Non-randomized clinical trial | 9 | 5 mg/kg q2w | GBM (6), Met (2), ODG (1) | GTV (6), SRT(2), EL (1), SRT (1), WBRT (1) PT (1) | 100% | Anemia, thrombocytopenia, lymphocytopenia, and/or neutropenia (3) | |
Sadraei et al., 2015. USA. [42] | Retrospective | 24 | 5 mg/kg q2w or 7.5 mg/kg q3w or 10 mg/kg q2w or 15 mg/kg q3w | Met (17), GBM (2), AVM (2), ODG (1), AE (1), TA (1) | WBRT (10), SRS (18), PT (1) | 95.8% | 95.8% | Grade 2 or less: hypertension, fatigue, urinary tract infection, and proteinuria (6). Grade 3: pulmonary embolism (1) |
Zhuang et al. China. 2016. [36] | Non-randomized clinical trial | 21 | 1 mg/kg q3w | Met (21) | SRS (16), WBRT (5) | 95.2% | 81% | Allergy (1), hypertension (1) |
Zhuang et al. China. 2016. [43] | Retrospective | 14 | 5 mg/kg q3-4w | Met (14) | STI (10), WBRT (4) | 92.9% | 83.3% | Allergy (1), hypertension (1) |
Weng et al., 2021. China. [37] | Retrospective | 22 | 3 mg/kg q2w | Met (22) | SRS (22) | 100% | None | |
Li et al., 2017. China. [44] | Retrospective | 50 | 5mg/kg q2w | NPC | RT | 76% | Not collected | |
Xu et al., 2018. China. [45] | Randomized, open label clinical trial | 58 | 5 mg/kg q2w | NPC | RT | 51.8% | 62.1% | Hypertension (12), fatigue (7), infection (4), hemorrhage (4), insomnia (3), headache (3), rash (3), fever (2), blurred vision (1), hyperglycemia (1), stroke (1) |
Alessandretti et al., 2021. Brazil. [46] | Retrospective | 2 | 5 mg/kg q2w | Met (2) | SRS (2) | 100% | 50% | None |
Glitza et al., 2017 USA. [47] | Retrospective | 7 | 5, 7.5, 10 mg/kg | Melanoma | SRS/WBRT | 57.4% | 71.5% | Arthralgia (1), dysgeusia (1) |
This study | Retrospective | 13 | 400 mg loading dose, 100 mg q4w maintenance dose | Met (11), MB (1), AVM (1) | SRS (8), SRT (5) | 100% | 11 | Hypertension (2), headache (2), mucositis oral (2), alopecia (2), diarrhea (1), epistaxis (1), proteinuria (1), wound dehiscence (1) |
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Tijtgat, J.; Calliauw, E.; Dirven, I.; Vounckx, M.; Kamel, R.; Vanbinst, A.M.; Everaert, H.; Seynaeve, L.; Van Den Berge, D.; Duerinck, J.; et al. Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series. Cancers 2023, 15, 2560. https://doi.org/10.3390/cancers15092560
Tijtgat J, Calliauw E, Dirven I, Vounckx M, Kamel R, Vanbinst AM, Everaert H, Seynaeve L, Van Den Berge D, Duerinck J, et al. Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series. Cancers. 2023; 15(9):2560. https://doi.org/10.3390/cancers15092560
Chicago/Turabian StyleTijtgat, Jens, Evan Calliauw, Iris Dirven, Manon Vounckx, Randa Kamel, Anne Marie Vanbinst, Hendrik Everaert, Laura Seynaeve, Dirk Van Den Berge, Johnny Duerinck, and et al. 2023. "Low-Dose Bevacizumab for the Treatment of Focal Radiation Necrosis of the Brain (fRNB): A Single-Center Case Series" Cancers 15, no. 9: 2560. https://doi.org/10.3390/cancers15092560