Perspectives on the model-based approach to proton therapy trials: A retrospective study of a lung cancer randomized trial

McNamara, Aimee L.; Hall, David C.; Shusharina, Nadya; Liu, Amy; Xiong, Wei; Ajdari, Ali; Mohan, Radhe; Liao, Zhongxing; Paganetti, Harald

doi:10.1016/j.radonc.2020.02.022

Cited by 8 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Publications addressing PT patient selection have been increasing since 2015. In order of the strength of evidence one publication was a systematic review, 13 five were government or medical college clinical indication lists, 18 , 19 , 20 , 21 , 22 eight were literature reviews, 4 , 5 , 6 , 10 , 15 , 30 , 31 , 32 five were prospective studies, 14 , 33 , 34 , 35 , 36 28 were retrospective studies, 3 , 7 , 11 , 12 , 16 , 23 , 25 , 26 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 one was a case‐control study, 57 and one was an expert opinion 58 . Thirty‐five publications were full‐text articles, nine were conference abstracts, and five were governm...…”

Section: Resultsmentioning

confidence: 99%

A scoping review of patient selection methods for proton therapy

Zientara

Giles

et al. 2021

J of Medical Radiation Sci

View full text Add to dashboard Cite

The aim was to explore various national and international clinical decisionmaking tools and dose comparison methods used for selecting cancer patients for proton versus X-ray radiation therapy. To address this aim, a literature search using defined scoping review methods was performed in Medline and Embase databases as well as grey literature. Articles published between 1 January 2015 and 4 August 2020 and those that clearly stated methods of proton versus X-ray therapy patient selection and those published in English were eligible for inclusion. In total, 321 studies were identified of which 49 articles met the study's inclusion criteria representing 13 countries. Six different clinical decision-making tools and 14 dose comparison methods were identified, demonstrating variability within countries and internationally. Proton therapy was indicated for all paediatric patients except those with lymphoma and re-irradiation where individualised model-based selection was required. The most commonly reported patient selection tools included the Normal Tissue Complication Probability model, followed by cost-effectiveness modelling and dosimetry comparison. Model-based selection methods were most commonly applied for head and neck clinical indications in adult cohorts (48% of studies). While no 'Gold Standard' currently exists for proton therapy patient selection with variations evidenced globally, some of the patient selection methods identified in this review can be used to inform future practice in Australia. As literature was not identified from all countries where proton therapy centres are available, further research is needed to evaluate patient selection methods in these jurisdictions for a comprehensive overview.

show abstract

Section: Resultsmentioning

confidence: 99%

A scoping review of patient selection methods for proton therapy

Zientara

Giles

et al. 2021

J of Medical Radiation Sci

View full text Add to dashboard Cite

show abstract

“…Secondary analyses of the data are ongoing to understand the role of various factors, including inter‐ and intra‐fractional variations in anatomy, the simplistic assumption about proton RBE, immature technology (PSPT instead of IMPT), and evolving treatment planning techniques. [ 55–65 ] At the same time a multi‐institutional randomized phase III study “Comparing Photon Therapy To Proton Therapy To Treat Patients With Lung Cancer” (NCT01993810) is underway through NRG and is nearing completion. Another phase II randomized trial “Image‐Guided, Intensity‐Modulated Photon or Proton Beam Radiation Therapy in Treating Patients with Stage II‐IIIB Non‐small Cell Lung Cancer” (NCT01629498) is also being conducted. For esophageal cancers, retrospective studies suggested reduced toxicity rates and promising disease control rates with proton therapy.…”

Section: Clinical Outcomesmentioning

confidence: 99%

A review of proton therapy – Current status and future directions

Mohan

2022

Precision Radiation Oncology

Self Cite

View full text Add to dashboard Cite

The original rationale for proton therapy was its highly conformal depth‐dose distributions compared to photons, which allow greater sparing of normal tissues and escalation of tumor doses, thus potentially improving outcomes. Additionally, recent research has revealed previously unrecognized advantages of proton therapy. For instance, the higher relative biological effectiveness (RBE) near the end of the proton range can be exploited to increase the difference in biologically effective dose in tumors versus normal tissues. Moreover, the smaller “dose bath,” that is, the compact nature of proton dose distributions, has been found to reduce the exposure of circulating lymphocytes and the immune organs at risk. There is emerging evidence that the resulting sparing of the immune system has the potential to improve outcomes. Protons accelerated to energies ranging from 70 to 250 MeV enter the treatment head mounted typically on a rotating gantry. Initially, the beams of protons are narrow and, to be suitable for treatments, must be spread laterally and longitudinally and shaped appropriately. Such spreading and shaping may be accomplished electro‐mechanically for the “passively scattered proton therapy” (PSPT) mode; or it may be achieved through magnetic scanning of thin “beamlets” of protons. Intensities of scanning beamlets are optimized to deliver intensity‐modulated proton therapy (IMPT), which optimally balances tumor dose and the sparing of normal tissues. IMPT is presumably the most powerful form of proton therapy. The planning and evaluation of proton dose distributions require substantially different techniques compared to photon therapy. This is mainly due to the fact that proton dose distributions are highly sensitive to inter‐ and intra‐fractional variations in anatomy. In addition, for the same physical dose, the biological effectiveness of protons is different from photons. In the current practice of proton therapy, the RBE is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a highly complex function of numerous variables including energy of protons, dose per fraction, tissue and its environment, cell type, end point, and possibly other factors. While the theoretical potential of proton therapy is high, the clinical evidence in support of its use has so far been mixed. The uncertainties and assumptions mentioned above and the limitations of the still evolving technology of proton therapy may have diminished its true clinical potential. Although promising results have been reported for many types of cancers, they are often based on small studies. At the same time, there have been reports of unforeseen toxicities. Furthermore, because of the high cost of proton therapy, questions are often raised about its value. The general consensus is that there is a need for continued improvement in the state of the art of proton therapy. There is also a need to generate high level evidence of the potential of protons. Fortuitously, such efforts are taking place curr...

show abstract

“…However, trials could be proposed for patients that fail to meet the ∆NTCP threshold. On the other hand, it could be mentioned that any attempt to implement an NTCP model-based approach failed for lung cancer due to too small NTCP differences between protons and photons [27]. Oinam et al [28] demonstrated that different NTCP calculation models, such as LKB or Niemerko model, could lead to significantly different toxicity predictions.…”

Section: Limitations Of Ntcp Modelsmentioning

confidence: 99%

Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives

Loap

Marzi

Mirandola

et al. 2021

Cancers

View full text Add to dashboard Cite

Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy.

show abstract

Perspectives on the model-based approach to proton therapy trials: A retrospective study of a lung cancer randomized trial

Cited by 8 publications

References 37 publications

A scoping review of patient selection methods for proton therapy

A scoping review of patient selection methods for proton therapy

A review of proton therapy – Current status and future directions

Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives

Contact Info

Product

Resources

About