scholarly journals Commissioning of a clinical pencil beam scanning proton therapy unit for ultra‐high dose rates (FLASH)

2021 ◽  
Author(s):  
Konrad P. Nesteruk ◽  
Michele Togno ◽  
Martin Grossmann ◽  
Anthony J. Lomax ◽  
Damien C. Weber ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1012
Author(s):  
Shannon Cunningham ◽  
Shelby McCauley ◽  
Kanimozhi Vairamani ◽  
Joseph Speth ◽  
Swati Girdhani ◽  
...  

Ultra-high dose rate radiation has been reported to produce a more favorable toxicity and tumor control profile compared to conventional dose rates that are used for patient treatment. So far, the so-called FLASH effect has been validated for electron, photon and scattered proton beam, but not yet for proton pencil beam scanning (PBS). Because PBS is the state-of-the-art delivery modality for proton therapy and constitutes a wide and growing installation base, we determined the benefit of FLASH PBS on skin and soft tissue toxicity. Using a pencil beam scanning nozzle and the plateau region of a 250 MeV proton beam, a uniform physical dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at various dose rates: Sham, Conventional (Conv, 1 Gy/s), Flash60 (57 Gy/s) and Flash115 (115 Gy/s). Acute radiation effects were quantified by measurements of plasma and skin levels of TGF-β1 and skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture as a surrogate of irradiation-induced skin and soft tissue toxicity and by plasma levels of 13 different cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF- β1). Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were all significantly decreased in FLASH compared to Conv groups of mice. FLASH and Conv PBS had similar efficacy with regards to growth control of MOC1 and MOC2 head and neck cancer cells transplanted into syngeneic, immunocompetent mice. These results demonstrate consistent delivery of FLASH PBS radiation from 1 to 115 Gy/s in a clinical gantry. Radiation response following delivery of 35 Gy indicates potential benefits of FLASH versus conventional PBS that are related to skin and soft tissue toxicity.


2020 ◽  
Vol 32 (6) ◽  
pp. 921-930
Author(s):  
Fritz R. Murray ◽  
James W. Snider ◽  
Ralf A. Schneider ◽  
Marc Walser ◽  
Alessandra Bolsi ◽  
...  

OBJECTIVEThe aim of this paper was to evaluate the prognostic factors in surgical and adjuvant care for spinal chordomas and chondrosarcomas after surgery followed by high-dose pencil-beam scanning proton therapy (PBS-PT).METHODSFrom 1997 to 2016, 155 patients (61 female patients; median age 55 years) with spinal (cervical, n = 61; thoracic, n = 29; lumbar, n = 13; sacral, n = 46; pelvic, n = 6) classic chordomas (n = 116) and chondrosarcomas (n = 39; most were low grade) were treated with maximal safe resection followed by PBS-PT (median dose prescribed: 74 Gy [relative biological effectiveness], range 48.6–77 Gy). The majority of patients (n = 153, 98.7%) had undergone at least 1 resection prior to PBS-PT (median 1, range 0–5; biopsy only, n = 2). Fewer than half (45.1%) of the surgeries were rated as gross-total resections (GTRs) prior to PBS-PT. Surgical stabilization (SS) was present in 39% of all patients (n = 60). Ninety-one patients (59%) presented with macroscopic tumor at the start of PBS-PT. The median follow-up duration was 64.7 months (range 12.2–204.8 months).RESULTSThe 5-year local tumor control, disease-free survival (DFS), and overall survival were 64.9% (95% CI 56.3%–73.5%), 59.4% (95% CI 50.6%–68.2%), and 77.9% (95% CI 70.6%–85.2%), respectively. In total, 63 patients (40.6%) experienced failure during the follow-up period: local only in 32 (20.6%), distal only in 7 (4.5%), local + distal in 19 (12.3%), surgical pathway failure (SPF) only in 2 (1.3%), local + SPF in 2 (1.3%), and distal + SPF in 1 (< 1%). Univariate analysis identified gross residual disease, the presence of SS, and treatment era prior to 2008 as highly significant for worse outcome, with all 3 remaining significant on multivariate analysis. The type of surgery (GTR or subtotal resection/biopsy) and whether GTR was achieved by en bloc or curettage did not show a significant prognostic effect. Surgical complications prior to PBS-PT were present in 42.5% of all surgically treated patients and were seen more commonly in patients with multiple surgical interventions (p = 0.005) and those operated on with the intent of en bloc resection (p = 0.006).CONCLUSIONSThe extent of resection and metallic stabilization substantially influenced clinical outcomes for patients with spinal chordoma or chondrosarcoma despite high-dose adjuvant PBS-PT. Optimal upfront surgical management of these tumors continues to include GTR, as possible, with prompt adjuvant proton therapy.


Author(s):  
Carla Winterhalter ◽  
Michele Togno ◽  
Konrad Pawel Nesteruk ◽  
Frank Emert ◽  
Serena Psoroulas ◽  
...  

2020 ◽  
Vol 93 (1107) ◽  
pp. 20190028 ◽  
Author(s):  
Melpomeni Kountouri ◽  
Alessia Pica ◽  
Marc Walser ◽  
Francesca Albertini ◽  
Alessandra Bolsi ◽  
...  

Objective: To assess the radiation-induced optic neuropathy (RION) prevalence, following high dose pencil beam scanning proton therapy (PBSPT) to skull base and head and neck (H&N) tumours Methods: Between 1999 and 2014, 216 adult patients, median age 47 years (range, 18–77), were treated with PBS PT for skull base or H&N malignancies, delivering ≥45 GyRBE to the optic nerve(s) (ON) and/or optic chiasma (OC). The median administered dose to the planning target volume was 74.0 GyRBE (range, 54.0–77.4). The median follow-up was 5.3 years (range, 0.8–15.9). Results: RION was observed in 14 (6.5%) patients at a median time of 13.2 months (range, 4.8–42.6) following PBSPT. Most (92.9%) of RION were symptomatic. Most affected patients (11/14; 79%) developed unilateral toxicity. Grade 4, 3, 2 and 1 toxicity was observed in 10, 2, 1 and 1 patients, respectively. On univariate analyses, age (<70 vs ≥70 years; p < 0.0001), hypertension (p = 0.0007) and tumour abutting the optic apparatus (p = 0.012) were associated with RION. OC’s V60 GyRBE was of border line significance (p = 0.06). None of the other evaluated OC–ON dose/volume metrics (Dmax, Dmean, V40-60) were significantly associated with this complication. Conclusion: These data suggest that high-dose PBS PT for skull base and H&N tumours is associated with a low prevalence of RION. Caution should be however exercised when treating elderly/hypertensive patients with tumours abutting the optic apparatus. Advances in knowledge: This is the first study reporting the risk of developing RION following proton therapy with PBS technique, demonstrating the safety of this treatment.


2021 ◽  
Vol 82 ◽  
pp. 134-143
Author(s):  
M. De Saint-Hubert ◽  
C. De Angelis ◽  
Ž. Knežević ◽  
B. Michalec ◽  
B. Reniers ◽  
...  

2015 ◽  
Vol 16 (6) ◽  
pp. 281-292 ◽  
Author(s):  
Liyong Lin ◽  
Minglei Kang ◽  
Sheng Huang ◽  
Rulon Mayer ◽  
Andrew Thomas ◽  
...  

2017 ◽  
Vol 42 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Ontida Apinorasethkul ◽  
Maura Kirk ◽  
Kevin Teo ◽  
Samuel Swisher-McClure ◽  
John N. Lukens ◽  
...  

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