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Cancers
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Proton Therapy for Cancer in the Era of Precision Medicine
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Proton Therapy for Cancer in the Era of Precision Medicine

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 8159

Special Issue Editors

Dr. Maryam Moteabbed

E-Mail Website
Guest Editor
1. Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA
2. Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
Interests: proton therapy; image-guided; MRI-guided; adaptive radiotherapy
Dr. Francesca Albertini

E-Mail Website
Guest Editor
Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
Interests: proton therapy; treatment planning; adaptive radiotherapy; QA; robustness evaluation

Special Issue Information

Dear Colleagues,

In the era of precision medicine, technology-driven improvements in both advanced image guidance and particle therapy are indispensable for further improving the quality and effectiveness of radiation therapy. Both techniques are capable of reducing treatment margins and therefore can also reduce the volume of normal tissue irradiated outside the target volume, allowing for safer and more effective delivery.

Due to slower technological advances, the potential clinical benefits of proton therapy are currently not fully realized. Large target margins and suboptimal beam directions mainly stem from the lack of onboard volumetric image guidance and daily online plan adaptation to mitigate the increased vulnerability of proton doses to uncertainties, e.g., anatomy and setup variations, motion, and range uncertainties, which are induced by the sharp dose gradients. Furthermore, the potentially varying relative biological effectiveness could introduce further ambiguities. These uncertainties, when combined with the relatively high cost of proton therapy, could impede the widespread clinical application of this potentially superior modality.

This Special Issue will highlight ongoing research aimed at overcoming the remaining hurdles and recognizing future developmental prospects in order to move towards precise and personalized medicine. The clinical availability of novel cutting-edge technology to facilitate online adaptive proton treatments, biologically driven optimization, and enhanced beam quality and range control at a reduced cost are examples of future research directions that will hopefully make precision proton therapy available to many more cancer patients around the world.

You may choose our Joint Special Issue in Current Oncology.

Dr. Maryam Moteabbed
Dr. Francesca Albertini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proton therapy
  • pencil beam scanning
  • image-guidance
  • synthetic CTs
  • adaptive therapy
  • range uncertainty
  • range verification
  • radiobiological modeling
  • outcome modelling
  • AI in radiotherapy

Published Papers (5 papers)

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Research

12 pages, 2675 KiB  
Article
The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis
by Maryam Moteabbed, Mislav Bobić, Harald Paganetti and Jason A. Efstathiou
Cancers 2024, 16(2), 330; https://doi.org/10.3390/cancers16020330 - 11 Jan 2024
Viewed by 1015
Abstract
Purpose: Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT [...] Read more.
Purpose: Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Methods: Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose–volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Results: Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22–25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. Conclusions: PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome. Full article
(This article belongs to the Special Issue Proton Therapy for Cancer in the Era of Precision Medicine)
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13 pages, 2410 KiB  
Article
Clinical Characterization of a Table Mounted Range Shifter Board for Synchrotron-Based Intensity Modulated Proton Therapy for Pediatric Craniospinal Irradiation
by William T. Hrinivich, Heng Li, Anh Tran, Sahaja Acharya, Matthew M. Ladra and Khadija Sheikh
Cancers 2023, 15(11), 2882; https://doi.org/10.3390/cancers15112882 - 23 May 2023
Viewed by 1161
Abstract
Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for [...] Read more.
Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI). Methods: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared. Results: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, −0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup. Conclusions: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center. Full article
(This article belongs to the Special Issue Proton Therapy for Cancer in the Era of Precision Medicine)
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11 pages, 502 KiB  
Article
Costs of Newly Funded Proton Therapy Using Time-Driven Activity-Based Costing in The Netherlands
by Yi Hsuan Chen, Hedwig M. Blommestein, Reinder Klazenga, Carin Uyl-de Groot and Marco van Vulpen
Cancers 2023, 15(2), 516; https://doi.org/10.3390/cancers15020516 - 14 Jan 2023
Cited by 1 | Viewed by 1823
Abstract
Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per [...] Read more.
Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. Methods: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. Results: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Conclusion: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. Full article
(This article belongs to the Special Issue Proton Therapy for Cancer in the Era of Precision Medicine)
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14 pages, 3149 KiB  
Article
Low-Dose Computed Tomography Scanning Protocols for Online Adaptive Proton Therapy of Head-and-Neck Cancers
by Konrad P. Nesteruk, Mislav Bobić, Gregory C. Sharp, Arthur Lalonde, Brian A. Winey, Lena Nenoff, Antony J. Lomax and Harald Paganetti
Cancers 2022, 14(20), 5155; https://doi.org/10.3390/cancers14205155 - 21 Oct 2022
Cited by 4 | Viewed by 1943
Abstract
Purpose: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. Methods: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2–165.9 mGy. The highest [...] Read more.
Purpose: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. Methods: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2–165.9 mGy. The highest value corresponds to the standard protocol used for CT simulations of 10 head-and-neck patients included in the study. The minimum value corresponds to the lowest achievable tube current of the GE Discovery RT scanner used for the study. For each patient and each low-dose protocol, the noise relative to the standard protocol, derived from phantom images, was applied to a virtual CT (vCT). The vCT was obtained from a daily CBCT scan corresponding to the fraction with the largest anatomical changes. We ran an established adaptive workflow twice for each low-dose protocol using a high-quality daily vCT and the corresponding low-dose synthetic vCT. For a relative comparison of the adaptation efficacy, two adapted plans were recalculated in the high-quality vCT and evaluated with the contours obtained through deformable registration of the planning CT. We also evaluated the accuracy of dose calculation in low-dose CT volumes using the standard CT protocol as reference. Results: The maximum differences in D98 between low-dose protocols and the standard protocol for the high-risk and low-risk CTV were found to be 0.6% and 0.3%, respectively. The difference in OAR sparing was up to 3%. The Dice similarity coefficient between propagated contours obtained with low-dose and standard protocols was above 0.982. The mean 2%/2 mm gamma pass rate for the lowest-dose image, using the standard protocol as reference, was found to be 99.99%. Conclusion: The differences between low-dose protocols and the standard scanning protocol were marginal. Thus, low-dose CT protocols are suitable for online adaptive proton therapy of head-and-neck cancers. As such, considering scanning protocols used in our clinic, the imaging dose associated with online adaption of head-and-neck cancers treated with protons can be reduced by a factor of 40. Full article
(This article belongs to the Special Issue Proton Therapy for Cancer in the Era of Precision Medicine)
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11 pages, 1651 KiB  
Article
Integrating Structure Propagation Uncertainties in the Optimization of Online Adaptive Proton Therapy Plans
by Lena Nenoff, Gregory Buti, Mislav Bobić, Arthur Lalonde, Konrad P. Nesteruk, Brian Winey, Gregory Charles Sharp, Atchar Sudhyadhom and Harald Paganetti
Cancers 2022, 14(16), 3926; https://doi.org/10.3390/cancers14163926 - 14 Aug 2022
Cited by 4 | Viewed by 1565
Abstract
Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with [...] Read more.
Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1–5 repeated images during treatment: ‘reference adaptation’, with structures drawn by a physician; ‘single-DIR adaptation’, using a single set of deformably propagated structures; ‘multi-DIR adaptation’, using robust planning with multiple deformed structure sets; ‘conservative adaptation’, using the intersection and union of all deformed structures; ‘probabilistic adaptation’, using the probability of a voxel belonging to the structure in the optimization weight; and ‘no adaptation’. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast ‘plausibility check’, and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable. Full article
(This article belongs to the Special Issue Proton Therapy for Cancer in the Era of Precision Medicine)
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