Cancers

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13 pages, 769 KiB

Open AccessArticle

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers

by Sayuri Bou, Shigeyuki Takamatsu, Sae Matsumoto, Satoko Asahi, Hitoshi Tatebe, Yoshitaka Sato, Mariko Kawamura, Satoshi Shibata, Tamaki Kondou, Yuji Tameshige, Yoshikazu Maeda, Makoto Sasaki, Kazutaka Yamamoto, Hajime Sunagozaka, Hiroyuki Aoyagi, Hiroyasu Tamamura, Satoshi Kobayashi and Toshifumi Gabata

Cancers 2022, 14(23), 5842; https://doi.org/10.3390/cancers14235842 - 26 Nov 2022

Cited by 1 | Viewed by 1256

Abstract

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicity [...] Read more.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38–90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8–82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient’s condition. The median follow-up of surviving patients was 63 months (range, 1–126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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15 pages, 5519 KiB

Open AccessArticle

Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids

by Max Naumann, Tabea Czempiel, Anna Jana Lößner, Kristin Pape, Elke Beyreuther, Steffen Löck, Stephan Drukewitz, Alexander Hennig, Cläre von Neubeck, Barbara Klink, Mechthild Krause, Doreen William, Daniel E. Stange, Rebecca Bütof and Antje Dietrich

Cancers 2022, 14(15), 3781; https://doi.org/10.3390/cancers14153781 - 03 Aug 2022

Cited by 3 | Viewed by 2231

Abstract

To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were [...] Read more.

To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1^nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravel potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational proton radiation research. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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11 pages, 3144 KiB

Open AccessArticle

Dose Profile Modulation of Proton Minibeam for Clinical Application

by Myeongsoo Kim, Ui-Jung Hwang, Kyeongyun Park, Dohyeon Kim, Hak Soo Kim, Sang Hyoun Choi, Jong Hwi Jeong, Dongho Shin, Se Byeong Lee, Joo-Young Kim, Tae Hyun Kim, Hye Jung Baek, Hojin Kim, Kihwan Kim, Sang Soo Kim and Young Kyung Lim

Cancers 2022, 14(12), 2888; https://doi.org/10.3390/cancers14122888 - 11 Jun 2022

Cited by 3 | Viewed by 1858

Abstract

The feasibility of proton minibeam radiation therapy (pMBRT) using a multislit collimator (MSC) and a scattering device was evaluated for clinical use at a clinical proton therapy facility. We fabricated, through Monte Carlo (MC) simulations, not only an MSC with a high peak-to-valley [...] Read more.

The feasibility of proton minibeam radiation therapy (pMBRT) using a multislit collimator (MSC) and a scattering device was evaluated for clinical use at a clinical proton therapy facility. We fabricated, through Monte Carlo (MC) simulations, not only an MSC with a high peak-to-valley dose ratio (PVDR) at the entrance of the proton beam, to prevent radiation toxicity, but also a scattering device to modulate the PVDR in depth. The slit width and center-to-center distance of the diverging MSC were 2.5 mm and 5.0 mm at the large end, respectively, and its thickness and available field size were 100 mm and 76 × 77.5 mm², respectively. Spatially fractionated dose distributions were measured at various depths using radiochromic EBT3 films and also tested on bacterial cells. MC simulation showed that the thicker the MSC, the higher the PVDR at the phantom surface. Dosimetric evaluations showed that lateral dose profiles varied according to the scatterer’s thickness, and the depths satisfying PVDR = 1.1 moved toward the surface as their thickness increased. The response of the bacterial cells to the proton minibeams’ depth was also established, in a manner similar to the dosimetric pattern. Conclusively, these results strongly suggest that pMBRT can be implemented in clinical centers by using MSC and scatterers. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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12 pages, 2794 KiB

Open AccessArticle

Influence of Beam Angle on Normal Tissue Complication Probability of Knowledge-Based Head and Neck Cancer Proton Planning

by Roni Hytönen, Reynald Vanderstraeten, Max Dahele and Wilko F. A. R. Verbakel

Cancers 2022, 14(12), 2849; https://doi.org/10.3390/cancers14122849 - 09 Jun 2022

Cited by 1 | Viewed by 1394

Abstract

Knowledge-based planning solutions have brought significant improvements in treatment planning. However, the performance of a proton-specific knowledge-based planning model in creating knowledge-based plans (KBPs) with beam angles differing from those used to train the model remains unexplored. We used a previously validated RapidPlanPT [...] Read more.

Knowledge-based planning solutions have brought significant improvements in treatment planning. However, the performance of a proton-specific knowledge-based planning model in creating knowledge-based plans (KBPs) with beam angles differing from those used to train the model remains unexplored. We used a previously validated RapidPlanPT model and scripting to create nine KBPs, one with default and eight with altered beam angles, for 10 recent oropharynx cancer patients. The altered-angle plans were compared against the default-angle ones in terms of grade 2 dysphagia and xerostomia normal tissue complication probability (NTCP), mean doses of several organs at risk, and dose homogeneity index (HI). As KBP could be suboptimal, a proof of principle automatic iterative optimizer (AIO) was added with the aim of reducing the plan NTCP. There were no statistically significant differences in NTCP or HI between default- and altered-angle KBPs, and the altered-angle plans showed a <1% reduction in NTCP. AIO was able to reduce the sum of grade 2 NTCPs in 66/90 cases with mean a reduction of 3.5 ± 1.8%. While the altered-angle plans saw greater benefit from AIO, both default- and altered-angle plans could be improved, indicating that the KBP model alone was not completely optimal to achieve the lowest NTCP. Overall, the data showed that the model was robust to the various beam arrangements within the range described in this analysis. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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13 pages, 1055 KiB

Open AccessArticle

A Patient Selection Approach Based on NTCP Models and DVH Parameters for Definitive Proton Therapy in Locally Advanced Sinonasal Cancer Patients

by Alfredo Mirandola, Stefania Russo, Maria Bonora, Barbara Vischioni, Anna Maria Camarda, Rossana Ingargiola, Silvia Molinelli, Sara Ronchi, Eleonora Rossi, Alessandro Vai, Nicola Alessandro Iacovelli, Juliette Thariat, Mario Ciocca and Ester Orlandi

Cancers 2022, 14(11), 2678; https://doi.org/10.3390/cancers14112678 - 28 May 2022

Cited by 6 | Viewed by 1757

Abstract

(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two [...] Read more.

(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the

Δ

NTCP and

Δ

DVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to

Δ

NTCP > 3% for at least one severe toxicity, 4 (18.2%) due to

Δ

NTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of

Δ

NTCP and

Δ

DVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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16 pages, 618 KiB

Open AccessArticle

Adaptive Proton Therapy of Pediatric Head and Neck Cases Using MRI-Based Synthetic CTs: Initial Experience of the Prospective KiAPT Study

by Christian Bäumer, Rezarta Frakulli, Jessica Kohl, Sindhu Nagaraja, Theresa Steinmeier, Rasin Worawongsakul and Beate Timmermann

Cancers 2022, 14(11), 2616; https://doi.org/10.3390/cancers14112616 - 25 May 2022

Cited by 3 | Viewed by 2219

Abstract

Background and Purpose: Interfractional anatomical changes might affect the outcome of proton therapy (PT). We aimed to prospectively evaluate the role of Magnetic Resonance Imaging (MRI) based adaptive PT for children with tumors of the head and neck and base of skull. Methods: [...] Read more.

Background and Purpose: Interfractional anatomical changes might affect the outcome of proton therapy (PT). We aimed to prospectively evaluate the role of Magnetic Resonance Imaging (MRI) based adaptive PT for children with tumors of the head and neck and base of skull. Methods: MRI verification images were acquired at half of the treatment course. A synthetic computed tomography (CT) image was created using this MRI and a deformable image registration (DIR) to the reference MRI. The methodology was verified with in-silico phantoms and validated using a clinical case with a shrinking cystic hygroma on the basis of dosimetric quantities of contoured structures. The dose distributions on the verification X-ray CT and on the synthetic CT were compared with a gamma-index test using global 2 mm/2% criteria. Results: Regarding the clinical validation case, the gamma-index pass rate was 98.3%. Eleven patients were included in the clinical study. The most common diagnosis was rhabdomyosarcoma (73%). Craniofacial tumor site was predominant in 64% of patients, followed by base of skull (18%). For one individual case the synthetic CT showed an increase in the median

D_{2}

and

D_{\max}

dose on the spinal cord from 20.5 GyRBE to 24.8 GyRBE and 14.7 GyRBE to 25.1 GyRBE, respectively. Otherwise, doses received by OARs remained relatively stable. Similarly, the target volume coverage seen by

D_{95 %}

and

V_{95 %}

remained unchanged. Conclusions: The method of transferring anatomical changes from MRIs to a synthetic CTs was successfully implemented and validated with simple, commonly available tools. In the frame of our early results on a small cohort, no clinical relevant deterioration for neither PTV coverage nor an increased dose burden to OARs occurred. However, the study will be continued to identify a pediatric patient cohort, which benefits from adaptive treatment planning. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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14 pages, 1670 KiB

Open AccessArticle

The Influence of Motion on the Delivery Accuracy When Comparing Actively Scanned Carbon Ions versus Protons at a Synchrotron-Based Radiotherapy Facility

by Franciska Lebbink, Markus Stock, Dietmar Georg and Barbara Knäusl

Cancers 2022, 14(7), 1788; https://doi.org/10.3390/cancers14071788 - 31 Mar 2022

Cited by 6 | Viewed by 1925

Abstract

Motion amplitudes, in need of mitigation for moving targets irradiated with pulsed carbon ions and protons, were identified to guide the decision on treatment and motion mitigation strategy. Measurements with PinPoint ionisation chambers positioned in an anthropomorphic breathing phantom were acquired to investigate [...] Read more.

Motion amplitudes, in need of mitigation for moving targets irradiated with pulsed carbon ions and protons, were identified to guide the decision on treatment and motion mitigation strategy. Measurements with PinPoint ionisation chambers positioned in an anthropomorphic breathing phantom were acquired to investigate different tumour motion scenarios, including rib and lung movements. The effect of beam delivery dynamics and spot characteristics was considered. The dose in the tumour centre was deteriorated up to 10% for carbon ions but only up to 5% for protons. Dose deviations in the penumbra increased by a factor of two when comparing carbon ions to protons, ranging from 2 to 30% for an increasing motion amplitude that was strongly dependent on the beam intensity. Layer rescanning was able to diminish the dose distortion caused by tumour motion, but an increase in spot size could reduce it even further to 5% within the target and 10% at the penumbra. An increased need for motion mitigation of carbon ions compared to protons was identified to assure target coverage and sparing of adjacent organs at risk in the penumbra region and outside the target. For the clinical implementation of moving target treatments at a synchrotron-based particle facility complex, time dependencies needed to be considered. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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13 pages, 1580 KiB

Open AccessArticle

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion

by Ching-Hsin Lee, An-Hsin Chen, Sheng-Ping Hung, Cheng-En Hsieh, Jeng-Hwei Tseng, Po-Jui Chen, Jen-Yu Cheng, Joseph Tung-Chieh Chang, Kun-Ming Chan, Shi-Ming Lin, Chen-Chun Lin, Wei-Ting Chen, Wan-Yu Chen and Bing-Shen Huang

Cancers 2022, 14(7), 1616; https://doi.org/10.3390/cancers14071616 - 23 Mar 2022

Cited by 1 | Viewed by 2007

Abstract

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. [...] Read more.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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12 pages, 912 KiB

Open AccessArticle

Proton Radiation Therapy for Nasopharyngeal Cancer Patients: Dosimetric and NTCP Evaluation Supporting Clinical Decision

by Alessandro Vai, Silvia Molinelli, Eleonora Rossi, Nicola Alessandro Iacovelli, Giuseppe Magro, Anna Cavallo, Emanuele Pignoli, Tiziana Rancati, Alfredo Mirandola, Stefania Russo, Rossana Ingargiola, Barbara Vischioni, Maria Bonora, Sara Ronchi, Mario Ciocca and Ester Orlandi

Cancers 2022, 14(5), 1109; https://doi.org/10.3390/cancers14051109 - 22 Feb 2022

Cited by 9 | Viewed by 2921

Abstract

(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy (IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and [...] Read more.

(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy (IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and differences in dose and normal tissue complication probability (ΔNTCPx-p) for 16 models were calculated. Patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results for 7/16 models describing the most clinically relevant endpoints, applying a model-specific ΔNTCPx-p threshold (15% to 5% depending on the severity of the complication) and a composite threshold (35%). In addition, a comprehensive toxicity score (CTS) was defined as the weighted sum of all 16 ΔNTCPx-p, where weights follow a clinical rationale. (3) Results: Dose deviations were in favor of IMPT (ΔD_mean ≥ 14% for cord, esophagus, brainstem, and glottic larynx). The risk of toxicity significantly decreased for xerostomia (−12.5%), brain necrosis (−2.3%), mucositis (−3.2%), tinnitus (−8.6%), hypothyroidism (−9.3%), and trismus (−5.4%). There were 40% of the patients that resulted as eligible for IMPT, with a greater advantage for T3–T4 staging. Significantly different CTS were observed in patients qualifying for IMPT. (4) Conclusions: The MBS strategy successfully drives the clinical identification of NPC patients, who are most likely to benefit from IMPT. CTS summarizes well the expected global gain. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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13 pages, 2269 KiB

Open AccessArticle

A Decision Support Tool to Optimize Selection of Head and Neck Cancer Patients for Proton Therapy

by Makbule Tambas, Hans Paul van der Laan, Arjen van der Schaaf, Roel J. H. M. Steenbakkers and Johannes Albertus Langendijk

Cancers 2022, 14(3), 681; https://doi.org/10.3390/cancers14030681 - 28 Jan 2022

Cited by 6 | Viewed by 2323

Abstract

Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at [...] Read more.

Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at a very early stage (immediately after delineation) to avoid delay in treatment initiation. A total of 151 HNC patients were included, of which 106 (70%) patients qualified for PT. Linear regression models for individual OARs were created to predict the D_mean to the OARs for VMAT and IMPT plans. The predictors were OAR volume percentages overlapping with target volumes. Then, actual and predicted plan comparison decisions were compared. Actual and predicted OAR D_mean (VMAT R² = 0.953, IMPT R² = 0.975) and NTCP values (VMAT R² = 0.986, IMPT R² = 0.992) were highly correlated. The sensitivity, specificity, PPV and NPV of the decision support tool were 64%, 87%, 92% and 51%, respectively. The expected toxicity reduction with IMPT can be predicted using only the delineation data. The probability of qualifying for PT is >90% when the tool indicates a positive outcome for PT. This tool will contribute significantly to a more effective selection of HNC patients for PT at a much earlier stage, reducing treatment delay. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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10 pages, 974 KiB

Open AccessArticle

Post-Irradiation Sinus Mucosa Disease in Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Proton Therapy

by Pei-Wen Wu, Chien-Chia Huang, Yun-Shien Lee, Yung-Chih Chou, Kang-Hsing Fan, Chien-Yu Lin, Bing-Shen Huang, Shih-Wei Yang, Chi-Che Huang, Po-Hung Chang, Ta-Jen Lee and Joseph Tung-Chieh Chang

Cancers 2022, 14(1), 225; https://doi.org/10.3390/cancers14010225 - 04 Jan 2022

Cited by 10 | Viewed by 2702

Abstract

In the past decade, patients with nasopharyngeal cancer (NPC) have been deemed candidates for proton radiotherapy, due to the large and comprehensive target volumes and the necessity for the retention of the surrounding healthy tissues. In this study, we aimed to compare the [...] Read more.

In the past decade, patients with nasopharyngeal cancer (NPC) have been deemed candidates for proton radiotherapy, due to the large and comprehensive target volumes and the necessity for the retention of the surrounding healthy tissues. In this study, we aimed to compare the incidence and severity of post-irradiation sinusitis by detecting sinus mucosa diseases (SMDs) via the magnetic resonance imaging (MRI) of patients with NPC after intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT). A total of 53 patients in the IMPT group and 54 patients in the VMAT group were enrolled in this study. There were significantly lower endoscopic scores and Lund–Mackay staging scores determined from MRI scans in the IMPT group during different follow-up periods. For the most vulnerable sinuses, the incidence and severity of SMD were the highest during the third post-radiotherapy month in both groups. These decreased steadily, and there was no significant increase in the incidence and severity of SMD during the second post-radiotherapy year in the IMPT group. Our data show that NPC patients with IMPT have a significantly lower incidence and decreased severity of SMD than those with VMAT. A better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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11 pages, 1663 KiB

Open AccessArticle

Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer—Single Institution Experience

by Pavel Vítek, Jiří Kubeš, Vladimír Vondráček, Michal Andrlik, Matěj Navrátíl, Radek Zapletal, Alexandra Haas, Kateřina Dědečková, Barbora Ondrová, Alexander Grebenyuk and Jozef Rosina

Cancers 2022, 14(1), 185; https://doi.org/10.3390/cancers14010185 - 31 Dec 2021

Cited by 1 | Viewed by 2276

Abstract

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few [...] Read more.

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1—tumour with margins plus involved lymph nodes; 2—regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014–August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32–35). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3–4 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy/ulceration grade 2 (26.5%) and grade 3–4 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3–4 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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14 pages, 1805 KiB

Open AccessArticle

Dosimetric Comparisons between Proton Beam Therapy and Modern Photon Radiation Techniques for Stage I Non-Small Cell Lung Cancer According to Tumor Location

by Unurjargal Bayasgalan, Sung Ho Moon, Tae Hyun Kim, Tae Yoon Kim, Seung Hyun Lee and Yang-Gun Suh

Cancers 2021, 13(24), 6356; https://doi.org/10.3390/cancers13246356 - 17 Dec 2021

Cited by 4 | Viewed by 2886

Abstract

Herein, we investigated the dosimetric benefits for proton beam therapy (PBT) over modern photon radiation techniques according to tumor location (central, peripheral, and close to the chest wall) for stage I non-small cell lung cancer (NSCLC) patients. A total of 42 patients with [...] Read more.

Herein, we investigated the dosimetric benefits for proton beam therapy (PBT) over modern photon radiation techniques according to tumor location (central, peripheral, and close to the chest wall) for stage I non-small cell lung cancer (NSCLC) patients. A total of 42 patients with stage I NSCLC were treated with PBT with a total dose of 50–70 Gy in four or 10 fractions considering the risk of treatment-related toxicities. Simulation plans for three-dimensional conformal radiation therapy (3D-CRT), static-field intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT) were retrospectively generated using the same treatment volumes as implemented in the PBT plans for these patients. Dosimetric improvements were observed with PBT as compared with all the photon-based radiation techniques with regards to the mean lung dose, lung V5 and V10, mean heart dose, and heart V5 and V10 in all locations. Moreover, lower radiation exposure to the chest wall was observed within PBT for peripherally located and close to the chest wall tumors. All radiotherapy modalities achieved clinically satisfactory treatment plans in the current study. Notably, the usage of PBT resulted in significant dosimetric improvements in the lung and heart over photon-based techniques at all tumor locations, including the periphery, for stage I NSCLC. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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13 pages, 4645 KiB

Open AccessArticle

CT-on-Rails Versus In-Room CBCT for Online Daily Adaptive Proton Therapy of Head-and-Neck Cancers

by Konrad P. Nesteruk, Mislav Bobić, Arthur Lalonde, Brian A. Winey, Antony J. Lomax and Harald Paganetti

Cancers 2021, 13(23), 5991; https://doi.org/10.3390/cancers13235991 - 28 Nov 2021

Cited by 16 | Viewed by 3451

Abstract

Purpose: To compare the efficacy of CT-on-rails versus in-room CBCT for daily adaptive proton therapy. Methods: We analyzed a cohort of ten head-and-neck patients with daily CBCT and corresponding virtual CT images. The necessity of moving the patient after a CT scan is [...] Read more.

Purpose: To compare the efficacy of CT-on-rails versus in-room CBCT for daily adaptive proton therapy. Methods: We analyzed a cohort of ten head-and-neck patients with daily CBCT and corresponding virtual CT images. The necessity of moving the patient after a CT scan is the most significant difference in the adaptation workflow, leading to an increased treatment execution uncertainty σ. It is a combination of the isocenter-matching σ_i and random patient movements induced by the couch motion σ_m. The former is assumed to never exceed 1 mm. For the latter, we studied three different scenarios with σ_m = 1, 2, and 3 mm. Accordingly, to mimic the adaptation workflow with CT-on-rails, we introduced random offsets after Monte-Carlo-based adaptation but before delivery of the adapted plan. Results: There were no significant differences in accumulated dose-volume histograms and dose distributions for σ_m = 1 and 2 mm. Offsets with σ_m = 3 mm resulted in underdosage to CTV and hot spots of considerable volume. Conclusion: Since σ_m typically does not exceed 2 mm for in-room CT, there is no clinically significant dosimetric difference between the two modalities for online adaptive therapy of head-and-neck patients. Therefore, in-room CT-on-rails can be considered a good alternative to CBCT for adaptive proton therapy. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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14 pages, 3209 KiB

Open AccessArticle

A Novel Proton Pencil Beam Scanning FLASH RT Delivery Method Enables Optimal OAR Sparing and Ultra-High Dose Rate Delivery: A Comprehensive Dosimetry Study for Lung Tumors

by Shouyi Wei, Haibo Lin, J. Isabelle Choi, Charles B. Simone II and Minglei Kang

Cancers 2021, 13(22), 5790; https://doi.org/10.3390/cancers13225790 - 18 Nov 2021

Cited by 23 | Viewed by 3731

Abstract

Purpose: While transmission proton beams have been demonstrated to achieve ultra-high dose rate FLASH therapy delivery, they are unable to spare normal tissues distal to the target. This study aims to compare FLASH treatment planning using single energy Bragg peak proton beams versus [...] Read more.

Purpose: While transmission proton beams have been demonstrated to achieve ultra-high dose rate FLASH therapy delivery, they are unable to spare normal tissues distal to the target. This study aims to compare FLASH treatment planning using single energy Bragg peak proton beams versus transmission proton beams in lung tumors and to evaluate Bragg peak plan optimization, characterize plan quality, and quantify organ-at-risk (OAR) sparing. Materials and Methods: Both Bragg peak and transmission plans were optimized using an in-house platform for 10 consecutive lung patients previously treated with proton stereotactic body radiation therapy (SBRT). To bring the dose rate up to the FLASH-RT threshold, Bragg peak plans with a minimum MU/spot of 1200 and transmission plans with a minimum MU/spot of 400 were developed. Two common prescriptions, 34 Gy in 1 fraction and 54 Gy in 3 fractions, were studied with the same beam arrangement for both Bragg peak and transmission plans (n = 40 plans). RTOG 0915 dosimetry metrics and dose rate metrics based on different dose rate calculations, including average dose rate (ADR), dose-averaged dose rate (DADR), and dose threshold dose rate (DTDR), were investigated. We then evaluated the effect of beam angular optimization on the Bragg peak plans to explore the potential for superior OAR sparing. Results: Bragg peak plans significantly reduced doses to several OAR dose parameters, including lung V_7.4Gy and V_7Gy by 32.0% (p < 0.01) and 30.4% (p < 0.01) for 34Gy/fx plans, respectively; and by 40.8% (p < 0.01) and 41.2% (p < 0.01) for 18Gy/fx plans, respectively, compared with transmission plans. Bragg peak plans have ~3% less in DADR and ~10% differences in mean OARs in DTDR and DADR relative to transmission plans due to the larger portion of lower dose regions of Bragg peak plans. With angular optimization, optimized Bragg peak plans can further reduce the lung V_7Gy by 20.7% (p < 0.01) and V_7.4Gy by 19.7% (p < 0.01) compared with Bragg peak plans without angular optimization while achieving a similar 3D dose rate distribution. Conclusion: The single-energy Bragg peak plans achieve superior dosimetry performances in OARs to transmission plans with comparable dose rate performances for lung cancer FLASH therapy. Beam angle optimization can further improve the OAR dosimetry parameters with similar 3D FLASH dose rate coverage. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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12 pages, 1295 KiB

Open AccessArticle

Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy

by Andreas Köthe, Loïc Feuvret, Damien Charles Weber, Sairos Safai, Antony John Lomax and Giovanni Fattori

Cancers 2021, 13(21), 5327; https://doi.org/10.3390/cancers13215327 - 23 Oct 2021

Cited by 6 | Viewed by 1770

Abstract

Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with [...] Read more.

Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 Gy_RBE to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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13 pages, 1304 KiB

Open AccessArticle

A Prospective Study on Health-Related Quality of Life and Patient-Reported Outcomes in Adult Brain Tumor Patients Treated with Pencil Beam Scanning Proton Therapy

by Stephanie G. C. Kroeze, Paul-Henry Mackeprang, Claudio De Angelis, Alessia Pica, Barbara Bachtiary, Ulrike L. Kliebsch and Damien C. Weber

Cancers 2021, 13(19), 4892; https://doi.org/10.3390/cancers13194892 - 29 Sep 2021

Cited by 3 | Viewed by 1663

Abstract

Proton therapy (PT) is delivered to complex brain tumors to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. This study aims to evaluate health-related quality of life (HRQOL) and [...] Read more.

Proton therapy (PT) is delivered to complex brain tumors to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. This study aims to evaluate health-related quality of life (HRQOL) and patient reported outcomes (PROs) in patients treated with PT for brain tumors. Adult patients with brain tumors treated with PT filled out the EORTC-QLQ-C30 and BN20 questionnaires up to three years following PT. Toxicity was scored using the CTCAE v4.03. QoL and PRO were correlated to clinical factors. Three-year overall survival, distant brain control and local control rates were 98%, 97% and 84%, respectively. No ≥G3 acute toxicity was observed. Late PT-related ≥G3 severe toxicity occurred in seven patients (5.7%). Lower global QoL scores after PT were significantly correlated to low Karnofsky performance status (KPS) before PT (p = 0.001), surgical complications before PT (p = 0.04) and progressive disease (p = 0.017). A low QLQ-30 summary score at one year follow-up was correlated to sex (p = 0.015), low KPS before PT (p < 0.001), and central nervous system symptoms before PT (p = 0.018). Reported QLQ-BN20 neurological symptoms were correlated to lower KPS at baseline (p < 0.001) and surgical complications before PT (p = 0.03). PT-related toxicity only influenced reported symptoms directly following PT, but not QoL. Although global QoL temporarily decreased after treatment, it improved again from one year onwards. Global QoL and reported symptoms over time were not correlated with the proton therapy and were more related to preexisting symptoms and progressive disease. This study assists in improving patient support in patients with brain tumors receiving PT. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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Review

Jump to: Research, Other

18 pages, 334 KiB

Open AccessReview

Proton Beam Therapy for Esophageal Cancer

by Jea Giezl N. Solidum, Raniv D. Rojo, Jennifer Y. Wo and Edward Christopher Dee

Cancers 2022, 14(16), 4045; https://doi.org/10.3390/cancers14164045 - 22 Aug 2022

Cited by 1 | Viewed by 2431

Abstract

Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at [...] Read more.

Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at risk. In addition, the anatomic location of the esophagus raises challenges for radiotherapy due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These challenges propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. Several dosimetric studies support the potential advantages of PBT for esophageal cancer treatment however, translation of these results to improved clinical outcomes remains unclear with limited clinical data, especially in large populations. Studies on the effect on quality of life are likewise lacking. Here, we review the existing and emerging role of PBT for esophageal cancer, including treatment planning, early clinical comparisons of PBT with photon-based techniques, recently concluded and ongoing clinical trials, challenges and toxicities, effects on quality of life, and global inequities in the treatment of esophageal cancer. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

14 pages, 321 KiB

Open AccessReview

Proton Therapy in the Management of Hepatocellular Carcinoma

by Jana M. Kobeissi, Lara Hilal, Charles B. Simone 2nd, Haibo Lin, Christopher H. Crane and Carla Hajj

Cancers 2022, 14(12), 2900; https://doi.org/10.3390/cancers14122900 - 12 Jun 2022

Cited by 4 | Viewed by 2449

Abstract

Proton radiation therapy plays a central role in the treatment of hepatocellular carcinoma (HCC). Because of the near-zero exit dose and improved sparing of normal liver parenchyma, protons are being used even in challenging scenarios, including larger or multifocal liver tumors, and those [...] Read more.

Proton radiation therapy plays a central role in the treatment of hepatocellular carcinoma (HCC). Because of the near-zero exit dose and improved sparing of normal liver parenchyma, protons are being used even in challenging scenarios, including larger or multifocal liver tumors, and those associated with vascular tumor thrombus. There is a mounting level of evidence that suggests that protons are superior to photons in terms of survival and toxicity outcomes, specifically the progression to liver failure. A randomized controlled trial comparing protons to photons is currently underway to verify this hypothesis. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

16 pages, 1135 KiB

Open AccessFeature PaperReview

Proton Therapy in the Management of Luminal Gastrointestinal Cancers: Esophagus, Stomach, and Anorectum

by Jana M. Kobeissi, Charles B. Simone II, Lara Hilal, Abraham J. Wu, Haibo Lin, Christopher H. Crane and Carla Hajj

Cancers 2022, 14(12), 2877; https://doi.org/10.3390/cancers14122877 - 10 Jun 2022

Viewed by 1669

Abstract

While the role of proton therapy in gastric cancer is marginal, its role in esophageal and anorectal cancers is expanding. In esophageal cancer, protons are superior in sparing the organs at risk, as shown by multiple dosimetric studies. Literature is conflicting regarding clinical [...] Read more.

While the role of proton therapy in gastric cancer is marginal, its role in esophageal and anorectal cancers is expanding. In esophageal cancer, protons are superior in sparing the organs at risk, as shown by multiple dosimetric studies. Literature is conflicting regarding clinical significance, but the preponderance of evidence suggests that protons yield similar or improved oncologic outcomes to photons at a decreased toxicity cost. Similarly, protons have improved sparing of the organs at risk in anorectal cancers, but clinical data is much more limited to date, and toxicity benefits have not yet been shown clinically. Large, randomized trials are currently underway for both disease sites. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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14 pages, 1057 KiB

Open AccessReview

Proton Therapy in the Management of Pancreatic Cancer

by Jana M. Kobeissi, Charles B. Simone II, Haibo Lin, Lara Hilal and Carla Hajj

Cancers 2022, 14(11), 2789; https://doi.org/10.3390/cancers14112789 - 04 Jun 2022

Cited by 4 | Viewed by 2670

Abstract

Radiation therapy plays a central role in the treatment of pancreatic cancer. While generally shown to be feasible, proton irradiation, particularly when an ablative dose is planned, remains a challenge, especially due to tumor motion and the proximity to organs at risk, like [...] Read more.

Radiation therapy plays a central role in the treatment of pancreatic cancer. While generally shown to be feasible, proton irradiation, particularly when an ablative dose is planned, remains a challenge, especially due to tumor motion and the proximity to organs at risk, like the stomach, duodenum, and bowel. Clinically, standard doses of proton radiation treatment have not been shown to be statistically different from photon radiation treatment in terms of oncologic outcomes and toxicity rates as per non-randomized comparative studies. Fractionation schedules and concurrent chemotherapy combinations are yet to be optimized for proton therapy and are the subject of ongoing trials. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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18 pages, 484 KiB

Open AccessFeature PaperReview

Proton Therapy for Squamous Cell Carcinoma of the Head and Neck: Early Clinical Experience and Current Challenges

by Sandra Nuyts, Heleen Bollen, Sweet Ping Ng, June Corry, Avraham Eisbruch, William M Mendenhall, Robert Smee, Primoz Strojan, Wai Tong Ng and Alfio Ferlito

Cancers 2022, 14(11), 2587; https://doi.org/10.3390/cancers14112587 - 24 May 2022

Cited by 11 | Viewed by 3446

Abstract

Proton therapy (PT) is a promising development in radiation oncology, with the potential to further improve outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC). By utilizing the finite range of protons, healthy tissue can be spared from beam [...] Read more.

Proton therapy (PT) is a promising development in radiation oncology, with the potential to further improve outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC). By utilizing the finite range of protons, healthy tissue can be spared from beam exit doses that would otherwise be irradiated with photon-based treatments. Current evidence on PT for HNSCC is limited to comparative dosimetric analyses and retrospective single-institution series. As a consequence, the recognized indications for the reimbursement of PT remain scarce in most countries. Nevertheless, approximately 100 PT centers are in operation worldwide, and initial experiences for HNSCC are being reported. This review aims to summarize the results of the early clinical experience with PT for HNSCC and the challenges that are currently faced. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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17 pages, 784 KiB

Open AccessReview

The Role of Hypofractionation in Proton Therapy

by Alexandre Santos, Scott Penfold, Peter Gorayski and Hien Le

Cancers 2022, 14(9), 2271; https://doi.org/10.3390/cancers14092271 - 02 May 2022

Cited by 5 | Viewed by 2556

Abstract

Hypofractionated radiotherapy is an attractive approach for minimizing patient burden and treatment cost. Technological advancements in external beam radiotherapy (EBRT) delivery and image guidance have resulted in improved targeting and conformality of the absorbed dose to the disease and a reduction in dose [...] Read more.

Hypofractionated radiotherapy is an attractive approach for minimizing patient burden and treatment cost. Technological advancements in external beam radiotherapy (EBRT) delivery and image guidance have resulted in improved targeting and conformality of the absorbed dose to the disease and a reduction in dose to healthy tissue. These advances in EBRT have led to an increasing adoption and interest in hypofractionation. Furthermore, for many treatment sites, proton beam therapy (PBT) provides an improved absorbed dose distribution compared to X-ray (photon) EBRT. In the past 10 years there has been a notable increase in reported clinical data involving hypofractionation with PBT, reflecting the interest in this treatment approach. This review will discuss the reported clinical data and radiobiology of hypofractionated PBT. Over 50 published manuscripts reporting clinical results involving hypofractionation and PBT were included in this review, ~90% of which were published since 2010. The most common treatment regions reported were prostate, lung and liver, making over 70% of the reported results. Many of the reported clinical data indicate that hypofractionated PBT can be well tolerated, however future clinical trials are still needed to determine the optimal fractionation regime. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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15 pages, 1644 KiB

Open AccessReview

Proton Therapy for Prostate Cancer: Challenges and Opportunities

by Darren M. C. Poon, Stephen Wu, Leon Ho, Kin Yin Cheung and Ben Yu

Cancers 2022, 14(4), 925; https://doi.org/10.3390/cancers14040925 - 13 Feb 2022

Cited by 6 | Viewed by 4483

Abstract

The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated [...] Read more.

The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated by the ASCENDE-RT trial. Alternatively, the lack of clinical benefits with PT may be attributable to improper dose delivery, mainly due to geometric and dosimetric uncertainties during treatment planning, as well as delivery procedures that compromise the dose conformity of treatments. Advanced high-precision PT technologies, and treatment planning and beam delivery techniques are being developed to address these uncertainties. For instance, external magnetic resonance imaging (MRI)-guided patient setup rooms are being developed to improve the accuracy of patient positioning for treatment. In-room MRI-guided patient positioning systems are also being investigated to improve the geometric accuracy of PT. Soon, high-dose rate beam delivery systems will shorten beam delivery time to within one breath hold, minimizing the effects of organ motion and patient movements. Dual-energy photon-counting computed tomography and high-resolution Monte Carlo-based treatment planning systems are available to minimize uncertainties in dose planning calculations. Advanced in-room treatment verification tools such as prompt gamma detector systems will be used to verify the depth of PT. Clinical implementation of these new technologies is expected to improve the accuracy and dose conformity of PT in the treatment of localized prostate cancers, and lead to better clinical outcomes. Improvement in dose conformity may also facilitate dose escalation, improving local control and implementation of hypofractionation treatment schemes to improve patient throughput and make PT more cost effective. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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Other

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24 pages, 3227 KiB

Open AccessSystematic Review

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review

by Mikaela Doig, Eva Bezak, Nayana Parange, Peter Gorayski, Victoria Bedford and Michala Short

Cancers 2022, 14(16), 3937; https://doi.org/10.3390/cancers14163937 - 15 Aug 2022

Cited by 1 | Viewed by 1670

Abstract

Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life [...] Read more.

Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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17 pages, 738 KiB

Open AccessSystematic Review

Medical Resource Use and Medical Costs for Radiotherapy-Related Adverse Effects: A Systematic Review

by Yi Hsuan Chen, Dominique Molenaar, Carin A. Uyl-de Groot, Marco van Vulpen and Hedwig M. Blommestein

Cancers 2022, 14(10), 2444; https://doi.org/10.3390/cancers14102444 - 16 May 2022

Cited by 2 | Viewed by 1998

Abstract

Background: Despite the need for a proper economic evaluation of new radiotherapies, the economic burden of radiotherapy-induced adverse effects remains unclear. A systematic review has been conducted to identify the existing evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects [...] Read more.

Background: Despite the need for a proper economic evaluation of new radiotherapies, the economic burden of radiotherapy-induced adverse effects remains unclear. A systematic review has been conducted to identify the existing evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and also to provide recommendations for including this evidence in economic evaluations. Methods: This systematic review of healthcare resource use and/or medical costs related to radiotherapy-induced adverse effects was performed up until 2020, focusing on patients with head and neck cancer, brain cancer, prostate cancer, eye cancer and breast cancer. Results: Resource use for treating the same adverse effects varied considerably across studies; for instance, the cost for mucositis ranged from USD 2949 to USD 17,244. This broad range could be related to differences in (1) severity of adverse effects in the study population, (2) study design, (3) cost estimation approach and (4) country and clinical practice. Conclusions: Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was being overestimated or underestimated in economic evaluation for radiotherapy. Full article

(This article belongs to the Special Issue Application of Proton Beam Therapy in Cancer Treatment)

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