Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies.
ABSTRACT: Background:Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging question. Despite developments in modern high-conformal photon techniques and proton beam therapy (PBT) are improving the normal tissues dose-sparing while maintaining satisfactory target coverage, clinical advantages supporting the optimal treatment strategy have to be better evaluated in long-term clinical studies and assessed in further radiobiological analyses. Our analysis aimed to systematically review current knowledge on the dosimetric advantages of PBT in the considered setting, which should be the basis for future specific studies. Materials and Methods:A PubMed and Google Scholar search was conducted in June 2019 to select dosimetric studies comparing photon versus proton RT for pediatric patients affected by CNS tumors. Then, a systematic review and meta-analysis according to the PRISMA statement was performed. Average and standard deviation values of Conformity Index, Homogeneity Index, and mean and maximum doses to intracranial and extracranial organs at risk (OARs) were specifically evaluated for secondary dosimetric comparisons. The standardized mean differences (SMDs) for target parameters and the mean differences (MDs) for OARs were summarized in forest plots (P < 0.05 was considered statistically significant). Publication bias was also assessed by the funnel plot and Egger's regression test. Results:Among the 88 identified papers, a total of twelve studies were included in the meta-analysis. PBT showed dosimetric advantages in target homogeneity (significant especially in the subgroup comparing PBT and 3D conformal RT), as well as in the dose sparing of almost all analyzed OARs (significantly superior results for brainstem, normal brain, and hippocampal dose constraints and for extracranial OARs parameters, excluding the kidneys). Publication bias was observed for Conformity Index. Conclusion:Our analysis supports the evidence of dosimetric advantages of PBT over photon RT, especially in the dose sparing of normal growing tissues. Confirmations from wider well-designed studies are required.
Project description:Radiation therapy (RT) has improved patient outcomes, but treatment-related complication rates remain high. In the conventional 2-dimensional and 3-dimensional conformal RT (3D-CRT) era, there was little room for toxicity reduction because of the need to balance the estimated toxicity to organs at risk (OARs), derived from dose-volume histogram data for organs including the lung, heart, spinal cord, and liver, with the planning target volume (PTV) dose. Intensity-modulated RT (IMRT) is an advanced form of conformal RT that utilizes computer-controlled linear accelerators to deliver precise radiation doses to the PTV. The dosimetric advantages of IMRT enable better sparing of normal tissues and OARs than is possible with 3D-CRT. A major breakthrough in the treatment of esophageal cancer (EC), whether early or locally advanced, is the use of proton beam therapy (PBT). Protons deposit their highest dose of radiation at the tumor, while leaving none behind; the resulting effective dose reduction to healthy tissues and OARs considerably reduces acute and delayed RT-related toxicity. In recent studies, PBT has been found to alleviate severe lymphopenia resulting from combined chemo-radiation, opening up the possibility of reducing immune suppression, which might be associated with a poor prognosis in cases of locally advanced EC.
Project description:PURPOSE:Radiation therapy (RT) improves control of Hodgkin lymphoma (HL), but patients who undergo RT are at risk for late effects, including cardiovascular disease and second cancers, because of radiation doses to organs at risk (OARs). Proton therapy (PT) can reduce OAR doses compared with conventional photon RT. However, access to PT is currently limited, so referrals must be appropriately selective. We aimed to identify subgroups of patients with HL who could benefit the most dosimetrically from RT with PT based on the prechemotherapy disease characteristics. METHODS AND MATERIALS:Normal tissue radiation doses were calculated for 21 patients with HL who were treated with deep-inspiration breath-hold pencil-beam scanning (PBS) PT and compared with doses from 3-dimensional conformal (3D-CRT) and partial arc volumetric modulated (PartArc) photon RT. Prechemotherapy disease characteristics associated with significant dosimetric benefits from PBS compared with photon RT were identified. RESULTS:Treatment with PBS was well tolerated and provided with good local control. PBS provided dosimetric advantages for patients whose clinical treatment volume extended below the seventh thoracic level and for female patients with axillary disease. In addition, an increasing dosimetric benefit for some OARs was observed for increasing target volume. PBS significantly reduced the mean dose to the heart, breast, lungs, spinal cord, and esophagus. Dose homogeneity and conformity within the target volume were also superior with PBS, but some high-dose measures and hot spots were increased with PBS compared with partial arc volumetric modulated photon RT. CONCLUSIONS:PBS gives good target coverage and local control while providing reductions in radiation dose to OARs for individuals who receive RT for HL compared with advanced photon RT. Our findings highlight groups of patients who would be expected to gain more dosimetric benefit from PBS. These findings facilitate the selection of patients who should be considered a priority for PT.
Project description:Although lung cancer rates are decreasing nationally, lung cancer remains the leading cause of cancer related death. Despite advancements in treatment and technology, overall survival (OS) for lung cancer remains poor. Proton beam therapy (PBT) is an advanced radiation therapy (RT) modality for treatment of lung cancer with the potential to achieve dose escalation to tumor while sparing critical structures due to higher target conformality. In early and late-stage non-small cell lung cancer (NSCLC), dosimetric studies demonstrated reduced doses to organs at risk (OARs) such as the lung, spinal cord, and heart, and clinical studies report limited toxicities with PBT, including hypofractionated regimens. In limited-stage SCLC, studies showed that regimens chemo RT including PBT were well tolerated, which may help optimize clinical outcomes. Improved toxicity profiles may be beneficial in post-operative radiotherapy, for which initial dosimetric and clinical data are encouraging. Sparing of OARs may also increase the proportion of patients able to complete reirradiation for recurrent disease. However, there are various challenges of using PBT including a higher financial burden on healthcare and limited data supporting its cost-effectiveness. Further studies are needed to identify subgroups that benefit from PBT based on prognostic factors, and to evaluate PBT combined with immunotherapy, in order to elucidate the benefit that PBT may offer future lung cancer patients.
Project description:BACKGROUND:This study aimed to contrast four different irradiation methods for pediatric medulloblastoma tumors in a dosimetric comparison regarding planning target volume (PTV) coverage and sparing of organs at risk (OARs). METHODS:In sum 24 treatment plans for 6 pediatric patients were realized. Besides the clinical standard of a 3D-conformal radiotherapy (3D-CRT) treatment plan taken as a reference, volumetric modulated arc therapy (VMAT) treatment plans ("VMAT_AVD" vs. "noAVD" vs. "FullArc") were optimized and calculated for each patient. For the thoracic and abdominal region, the short partial-arc VMAT_AVD technique uses an arc setup with reduced arc-length by 100°, using posterior and lateral beam entries. The noAVD uses a half 180° (posterior to lateral directions) and the FullArc uses a full 360° arc setup arrangement. The prescription dose was set to 35.2 Gy. RESULTS:We identified a more conformal dose coverage for PTVs and a better sparing of OARs with used VMAT methods. For VMAT_AVD mean dose reductions in organs at risk can be realized, from 16 to 6.6 Gy, from 27.1 to 8.7 Gy and from 8.0 to 1.9 Gy for the heart, the thyroid and the gonads respectively, compared to the 3D-CRT treatment method. In addition we have found out a superiority of VMAT_AVD compared to the noAVD and FullArc trials with lower exposure to low-dose radiation to the lungs and breasts. CONCLUSIONS:With the short partial-arc VMAT_AVD technique, dose exposures to radiosensitive OARS like the heart, the thyroid or the gonads can be reduced and therefore, maybe the occurrence of late sequelae is less likely. Furthermore the PTV conformity is increased. The advantages of the VMAT_AVD have to be weighed against the potentially risks induced by an increased low dose exposure compared to the 3D-CRT method.
Project description:This study aimed to compare the post-modified radical mastectomy radiotherapy (PMRMRT) for left-sided breast cancer utilizing 3-dimensional conformal radiotherapy with field-in-field technique (3DCRT-FinF), 5-field intensity-modulated radiation therapy (5F-IMRT) and 2- partial arc volumetric modulated arc therapy (2P-VMAT). We created the 3 different PMRMRT plans for each of the ten consecutive patients. We performed Kruskal-Wallis analysis of variance (ANOVA) followed by the Dunn's-type multiple comparisons to establish a hierarchy in terms of plan quality and dosimetric benefits. P < 0.05 was considered statistically significant. Both 5F-IMRT and 2P-VMAT plans exhibited similar PTV coverage (V95%), hotspot areas (V110%) and conformity (all p > 0.05), and significantly higher PTV coverage compared with 3DCRT-FinF (both p < 0.001). In addition, 5F-IMRT plans provided significantly less heart and left lung radiation exposure than 2P-VMAT (all p < 0.05). The 3DCRT-FinF plans with accurately estimated CTV displacement exhibited enhanced target coverage but worse organs at risk (OARs) sparing compared with those plans with underestimated displacements. Our results indicate that 5F-IMRT has dosimetrical advantages compared with the other two techniques in PMRMRT for left-sided breast cancer given its optimal balance between PTV coverage and OAR sparing (especially heart sparing). Individually quantifying and minimizing CTV displacement can significantly improve dosage distribution.
Project description:To compare dosimetric parameters of intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and tomotherapy (TOMO) in the adjuvant treatment of gastroesophageal junction (GEJ)/stomach cancer. The planning goal was to maintain high target coverage while keeping the dose to the bowel and bone marrow (BM) as low as possible.After curative surgery, 16 patients with GEJ/stomach cancer were re-planned by coplanar IMRT (five fixed beam), VMAT (double-arc), and TOMO. The dose to the planning target volume (PTV) was 45 Gy in 25 fractions. The target parameters, including the homogeneity index (HI) and conformity index (CI), and doses to the organs at risk (OARs) were analyzed.Dosimetric parameters for PTV and OARs were comparable among the three techniques. However, TOMO provided improved conformity (CI = 0.92±0.03) and homogeneity (HI = 1.07±0.02) than IMRT (CI = 0.87±0.03; HI = 1.09±0.02; p < 0.05) and VMAT (CI = 0.86±0.03; HI = 1.09±0.02; p < 0.01). TOMO also improved dose sparing of the bowel (percentage of the volume receiving a dose of ? 30 Gy [V30] = 23.24±9.85) and BM (V30 = 71.66±6.15) compared with IMRT (bowel V30 = 30.02±11.74; BM V30 = 83.74±8.42; p < 0.01) and VMAT (bowel V30 = 31.88±11.59; BM V30 = 79.51±9.07; p < 0.01).TOMO is a good option for adjuvant treatment of GEJ/stomach cancer in patients undergoing radical surgery due to its superior bowel and BM dose sparing, dose conformity and dose homogeneity; however, future studies are required to validate its clinical efficacy.
Project description:The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole-brain radiotherapy (NC-WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole-brain planning target volume (WB-PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam-on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0± 0.4Gy, respectively. Accordingly, WB-PTV received the prescription dose of 30Gy and mean V30 was 90.5% ± 0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy, and 15.6 ± 0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ± 0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC-WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC-WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719 ± 44 and 2.34 ± 0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1 ± 0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases.
Project description:OBJECTIVE: To compare the dosimetric results and treatment delivery efficiency among RapidArc® (Varian Medical Systems, Palo Alto, CA), 7-field intensity-modulated radiotherapy (7-f IMRT) and 9-field IMRT (9-f IMRT) with hypofractionated simultaneous integrated boost to the prostate. METHODS: RapidArc, 7-f IMRT and 9-f IMRT plans were created for 21 consecutive patients treated for high-risk prostate cancer using the Eclipse™ treatment planning system (Varian Medical Systems). All plans were designed to deliver 70.0 Gy in 28 fractions to the prostate planning target volume (PTV) while simultaneously delivering 50.4 Gy in 28 fractions to the pelvic nodal PTV. Target coverage and sparing of organs at risk (OARs) were compared across techniques. The total number of monitor units (MUs) and the treatment time were used to assess treatment delivery efficiency. RESULTS: RapidArc resulted in slightly superior conformity and homogeneity of prostate PTV, whereas all plans were comparable with respect to dose to the nodal PTV. Although OARs sparing for RapidArc and 7-f IMRT plans were almost equivalent, 9-f IMRT achieved better sparing of the rectum and bladder than RapidArc and 7-f IMRT. RapidArc provided the highest treatment delivery efficiency with the lowest MUs and shortest treatment time. CONCLUSION: RapidArc resulted in similar OAR sparing to 7-f IMRT, whereas 9-f IMRT provided the best OAR sparing. Treatment delivery efficiency is significantly higher for RapidArc. ADVANCES IN KNOWLEDGE: This study validated the feasibility and limitations of RapidArc in the treatment of high-risk prostate cancer with complex pelvic target volumes.
Project description:Background:Proton beam therapy (PBT) delivers high-energy radiation to target tumours while sparing surrounding normal tissues. The dosimetric advantages of PBT over traditional photon radiotherapy may be clear but the translation of this benefit into clinically meaningful reductions in toxicities and improved quality-of-life (QoL) needs to be determined. Randomised controlled trials (RCTs) are considered the gold standard for generating the highest-level evidence in medicine. The objectives of this systematic review were to provide an overview of published clinical studies evaluating the benefits of PBT, and to examine the methodology used in clinical trials with respect to study design and outcomes. Methods:PubMed, EMBASE and Cochrane databases were systematically searched for published clinical studies where PBT was a cancer treatment intervention. All randomised and non-randomised studies, prospective or retrospective, were eligible for inclusion. Results:In total, 219 studies were included. Prospective studies comprised 89/219 (41%), and of these, the number of randomised phase II and III trials were 5/89 (6%) and 3/89 (3%) respectively. Of all the phase II and III trials, 18/24 (75%) were conducted at a single PBT centre. Over one-third of authors recommended an increase in length of follow up. Research design and/or findings were poorly reported in 74/89 (83%) of prospective studies. Patient reported outcomes were assessed in only 19/89 (21%) of prospective studies. Conclusions:Prospective randomised evidence for PBT is limited. The set-up of national PBT services in several countries provides an opportunity to guide the optimal design of prospective studies, including RCTs, to evaluate the benefits of PBT across various disease sites. Collaboration between PBT centres, both nationally and internationally, would increase potential for the generation of practice changing evidence. There is a need to facilitate and guide the collection and analysis of meaningful outcome data, including late toxicities and patient reported QoL.
Project description:During breast/chest wall and regional nodal irradiation (RNI), standard 3D conformal techniques can fail to meet the dosimetric constraints for the heart and ipsilateral lung. VMAT can improve the dosimetric sparing of the heart and lungs. However the unnecessary increase in dose to the organs in the supraclavicular region as a result of using VMAT can be avoided. In this work we investigate potential dosimetric advantages of combining 3D with VMAT to improve sparing of these organs. Ten breast cancer patients requiring radiation therapy to the breast/chest wall and RNI including the IMNs, and who did not have a viable 3D conformal plan were chosen for the study. Each patient was planned with VMAT and with a combination of 3D for the supraclavicular region and VMAT for the breast/chest wall followed by a dosimetric comparison. Prescription dose was 50.4 Gy in 28 fractions. For similar coverage to the PTV and IMNs, doses to the esophagus and cord were reduced by 17.8 Gy and 15.5 Gy while mean dose to the thyroid and larynx were also reduced by 16.5 Gy and 11.7 Gy respectively. Maximum brachial plexus dose was the same in both techniques. The ipsilateral lung V20Gy increased by 3.1% but was still < 30%. No significant differences were noted in doses to the heart, total lung and contralateral breast. However V5Gy to the contralateral lung was reduced by 8.5% with the combined plan. Using 3D conformal planning for the supraclavicular region and VMAT over the breast/chest wall improves sparing of the esophagus, cord, thyroid and larynx while reducing low dose exposure to the contralateral lung and does not compromise doses to the heart, ipsilateral lung and total lung.