Intensity-modulated Proton Beam Therapy Research Articles

Dose Evaluation in 2-Phase Method for Advanced Esophageal Cancer by Hybrid Irradiation Techniques

PurposeIn concurrent chemoradiotherapy for advanced esophageal cancer, a 2-phase method consisting of initial irradiation of a wide elective nodal region and boost irradiation of the primary lesion is commonly employed. Although dose escalation to the primary lesion may be required to achieve higher local control rates, the radiation dose to critical organs must not exceed dose constraints. To achieve an optimum balance of dose prescription and dose reduction to surrounding organs, such as the lungs and heart, we compared hybrid dose distributions and investigated the best combination of the following recent irradiation techniques: volumetric modulation arc therapy (VMAT), proton broad-beam irradiation, and intensity-modulated proton beam therapy (IMPT). Materials and MethodsForty-five patients with advanced esophageal cancer whose primary lesions were located in the middle- or lower-thoracic region were studied. Radiotherapy plans for the initial and boost irradiation in the 2-phase method were calculated using VMAT, proton broad-beam irradiation, and IMPT calculation codes, and the dose-volume histogram indices of the lungs and heart for the accumulated plans were compared. ResultsIn plans using boost proton irradiation with a prescribed dose of 60 Gy(RBE), all dose-volume histogram indices were significantly below the tolerance limits. Initial and boost irradiation with VMAT resulted in the median dose of V30 Gy(RBE)(heart) of 27.4% and an achievement rate below the tolerance limit of 57.8% (26 cases). In simulations of dose escalation up to 70 Gy(RBE), initial and boost IMPT resulted in the highest achievement rate, satisfying all dose constraints in 95.6% (43 cases). ConclusionApplying VMAT to both initial and boost irradiation is not recommended because of the increased risk of the cardiac dose exceeding the tolerance limit. IMPT may allow dose escalation of up to 70 Gy(RBE) without radiation risks to the lungs and heart in the treatment of advanced esophageal cancer.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

Comparison of passive-scattered and intensity-modulated proton beam therapy of craniospinal irradiation with proton beams for pediatric and young adult patients with brain tumors

PurposeTo investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT).Methods and materialsTwenty-four pediatric and young adult brain tumor patients (age: 1–24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated.ResultsThe minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial–caudal direction (p = 0.000–0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000–0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000–0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000–0.022).ConclusionsThe PTV doses of IMPT and PSPT are robust and stable in both anterior–posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial–caudal movements.Trial registryClinical Trial Registration number: No. 04-03.

Feasibility Study of Robust Treatment Planning in VMAT for Head and Neck Cancer

In general, patient positional uncertainty is considered by adding a geometrically expanded margin to clinical target volume (CTV) in photon radiation therapy. However, this method may not be suitable because image-guided radiotherapy is available. In intensity modulated proton beam therapy, robust treatment planning is currently common to take patient positional uncertainty into account in optimization rather than in margins. The purpose of this study is to assess the feasibility of clinical implementation of the method in volumetric modulated arc therapy (VMAT) for head and neck cancer. We quantitatively evaluated whether the plans with the robust optimization (Robust plans) can adequately cover CTV against patients' positional uncertainties and body shape change throughout a treatment course. Ten head and neck cancer patients were chosen, who were treated with PTV-based VMAT plans in our hospital between 2021.5-2022.4. RayStation V10A (RaySearch Laboratories, Stockholm, Sweden) was used for the robust optimization, which was applied to the CTVs with patient positional uncertainty of 5 mm in the 6-axis direction. Dose prescribed to the high- and low-risk CTVs were to 70 and 56 Gy in 35 fractions, respectively. To create the patients' CT images with residual set-up errors and body shape change at the treatment, pseudo simulation-CT images were created by deformable image registration with CBCT and simulation-CT. Dose distribution at the treatment was re-calculated by applying the plan to the pseudo simulation-CT images. The variation of D98 for the high-risk CTV from the time of treatment planning was evaluated on a weekly basis. For comparison, planning target volume (PTV) -based plans (5 mm margin circumference) were created and a similar evaluation was performed. D98 for the high-risk CTV varied between -3∼2% in the robust plan and between -5∼1% in the PTV-based plan during the treatment course. There was no significant difference in the amount of D98 variation between the two plans by t-test, except for one case with hypopharyngeal cancer. In this case, D98 for the high-risk CTV varied within ±1% with the PTV-based plan, whereas the value decreased up to 3% with the robust plan (p < 0.05). This case often had a residual setup error of approximately 5 mm at the sites related to the pitch rotation of head, suggesting that the dose distribution for the robust plan was affected by non-rigid positional errors. Patient weight loss during the treatment period was -3.5±2.4 kg, showing a weak correlation (r = -0.33) with the variation in D98 for the high-risk CTV. The robust treatment planning exhibits comparable CTV coverage to the conventional PTV-based planning against positional uncertainty and body shape change throughout a treatment period. In order to overcome set-up baseline shift by the non-rigid positional errors, re-planning should be recommended. Further planning studies will be conducted to promote clinical implementation of the method.

Comparison of Craniospinal Irradiation Using Proton Beams According to Irradiation Method and Initial Experience Treating Pediatric Patients

This study compared craniospinal irradiation using proton beam therapy (PBT) according to irradiation method and investigated the initial effects. Twenty-four pediatric patients (1-24 years old) who received proton craniospinal irradiation were examined. Passive scattered PBT (PSPT) and intensity modulated PBT (IMPT) were used in 8 and 16 patients, respectively. The whole vertebral body technique was used for 13 patients <10 years old, and the vertebral body sparing (VBS) technique was used for the remaining 11 patients aged ≥10 years. The follow-up period was 17 to 44 (median, 27) months. Organ-at-risk and planning target volume (PTV) doses and other clinical data were examined. The maximum lens dose using IMPT was lower than that using PSPT (P=.008). The mean thyroid, lung, esophagus, and kidney doses were lower in patients treated using the VBS technique compared with the whole vertebral body technique (all P < .001). The minimum PTV dose of IMPT was higher than that of PSPT (P=.01). The inhomogeneity index of IMPT was lower than that of PSPT (P=.004). IMPT is better than PSPT at reducing the dose to the lens. The VBS technique can decrease the doses to neck-chest-abdomen organs. The PTV coverage of IMPT is superior to that of PSPT.

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions

BackgroundIntensity modulated proton beam therapy (IMPT) for head and neck cancer offers dosimetric benefits for the organs at risk when compared to photon-based volumetric modulated arch therapy (VMAT). However, limited data exists about the potential benefits of IMPT for tooth-bearing regions.The aim of this study was to compare the IMPT and VMAT radiation dosimetrics of the tooth-bearing regions in head and neck cancer patients. Also, we aimed to identify prognostic factors for a cumulative radiation dose of ≥40 Gy on the tooth-bearing areas, which is considered the threshold dose for prophylactic dental extractions. MethodsA total of 121 head and neck cancer patients were included in this retrospective analysis of prospectively collected data. We compared the average Dmean values of IMPT versus VMAT of multiple tooth-bearing regions in the same patients. Multivariate logistic regression analysis was performed for receiving a cumulative radiation dose of ≥40 Gy to the tooth-bearing regions (primary endpoint) in both VMAT and IMPT. ResultsA lower Dmean was seen after applying IMPT to the tooth-bearing tumour regions (p < 0.001). Regarding VMAT, oral cavity tumours, T3-T4 tumours, molar regions in the mandible, and regions ipsilateral to the tumour were risk factors for receiving a cumulative radiation dose of ≥40 Gy. ConclusionsIMPT significantly reduces the radiation dose to the tooth-bearing regions.

Treatment Tolerability and Toxicity of Postoperative Proton Beam Therapy for Gynecologic Malignancies: Results of the Prospective Phase 2 APROVE Trial

The APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women with uterine cervical or endometrial cancer. In this analysis, we report the primary study endpoint of safety and treatment tolerability as well as toxicity rates and progression-free survival (PFS). 25 patients were treated with postoperative proton beam therapy with a total dose of 45 to 50.4 Gy (RBE) in 5 to 6×1.8 Gy (RBE) fractions weekly using active raster-scanning intensity modulated proton beam therapy (IMPT). Sequential or simultaneous platinum-based chemotherapy was administered if indicated. The primary endpoint was defined as the lack of any acute ≥grade 3 gastrointestinal (GI) or urogenital (GU) toxicity according to the Common Terminology Criteria for Adverse Events v 4.0 or premature treatment abortion. Secondary endpoints were clinical symptoms and toxicity, quality of life, and PFS. All patients completed IMPT according to the protocol, with a median treatment duration of 43 days (range, 33 to 51 days). No patient developed gastrointestinal or genitourinary toxicity ≥grade 3, and the treatment tolerability rate was 100%. Therefore, the null hypothesis H0: Tolerability Rate ≤80% could be rejected in favor of the alternative hypothesis H1: Tolerability rate >80% using an exact binomial test with a one-sided significance level of α=10% (one-sided P value P=.0059). The median follow-up time after the end of IMPT was 25.1 months (range, 20.2 to 50.3 months). 18 of 25 (75%) patients completed the study follow-up of 24 months. 7 patients had progressive disease. Kaplan-Meier-estimated mean PFS was 39.9 months (95% confidence interval: 33.37 to 46.5 months). Postoperative IMPT is a safe treatment option for cervical and endometrial cancer patients, with only low-grade acute and late toxicities. Larger randomized trials are necessary to further assess the potential of IMPT and improve patient selection.

Is an Endorectal Balloon Beneficial for Rectal Sparing after Spacer Implantation in Prostate Cancer Patients Treated with Hypofractionated Intensity-Modulated Proton Beam Therapy? A Dosimetric and Radiobiological Comparison Study.

The aim of this study is to examine the dosimetric influence of endorectal balloons (ERB) on rectal sparing in prostate cancer patients with implanted hydrogel rectum spacers treated with dose-escalated or hypofractionated intensity-modulated proton beam therapy (IMPT). Ten patients with localized prostate cancer included in the ProRegPros study and treated at our center were investigated. All patients underwent placement of hydrogel rectum spacers before planning. Two planning CTs (with and without 120 cm3 fluid-filled ERB) were applied for each patient. Dose prescription was set according to the h strategy, with 72 Gray (Gy)/2.4 Gy/5× weekly to prostate + 1 cm of the seminal vesicle, and 60 Gy/2 Gy/5× weekly to prostate + 2 cm of the seminal vesicle. Planning with two laterally opposed IMPT beams was performed in both CTs. Rectal dosimetry values including dose-volume statistics and normal tissue complication probability (NTCP) were compared for both plans (non-ERB plans vs. ERB plans). For ERB plans compared with non-ERB, the reductions were 8.51 ± 5.25 Gy (RBE) (p = 0.000) and 15.76 ± 11.11 Gy (p = 0.001) for the mean and the median rectal doses, respectively. No significant reductions in rectal volumes were found after high dose levels. The use of ERB resulted in significant reduction in rectal volume after receiving 50 Gy (RBE), 40 Gy (RBE), 30 Gy (RBE), 20 Gy (RBE), and 10 Gy (RBE) with p values of 0.034, 0.008, 0.003, 0.001, and 0.001, respectively. No differences between ERB and non-ERB plans for the anterior rectum were observed. ERB reduced posterior rectal volumes in patients who received 30 Gy (RBE), 20 Gy (RBE), or 10 Gy (RBE), with p values of 0.019, 0.003, and 0.001, respectively. According to the NTCP models, no significant reductions were observed in mean or median rectal toxicity (late rectal bleeding ≥ 2, necrosis or stenosis, and late rectal toxicity ≥ 3) when using the ERB. ERB reduced rectal volumes exposed to intermediate or low dose levels. However, no significant reduction in rectal volume was observed in patients receiving high or intermediate doses. There was no benefit and also no disadvantage associated with the use of ERB for late rectal toxicity, according to available NTCP models.

TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.

Dosimetric feasibility of moderately hypofractionated/dose escalated radiation therapy for localised prostate cancer with intensity-modulated proton beam therapy using simultaneous integrated boost (SIB-IMPT) and impact of hydrogel prostate-rectum spacer

PurposeTo examine the dosimetric feasibility of hypofractionated/dose escalated radiation therapy in patients with localized prostate carcinoma using simultaneous integrated boost intensity-modulated proton beam therapy (SIB-IMPT) in absence or presence of prostate-rectum spacer.MethodsIMPT technique was implemented in 23 patients with intermediate- and high-risk prostate cancer treated at West German Proton Therapy Centre from March 2016 till June 2018, using SIB technique prescribing 60 GyRBE and 72 GyRBE in 30 fractions to PTV1 (prostate and seminal vesicle) and PTV2 boost (prostate and proximal seminal vesicle), respectively. In 15 patients, a transperineal injection of hydrogel was applied prior to radiotherapy to increase the distance between prostate and rectum. Planning and all treatments were performed with a 120 ml fluid-filled endorectal balloon customised daily for each patient. For each patient, 2 lateral IMPT beams were implemented taking a field-specific range uncertainty (RU) into account. Dose volume histograms (DVH) were analyzed for PTV2, PTV2 with range uncertainty margin (PTV2RU), rectum, bladder, right/left femoral heads, and penile bulb. For late rectal toxicities, the normal tissue complication probabilities (NTCP) were calculated using different biological models. A DVH- and NTCP-based dosimetric comparison was carried out between non-spacer and spacer groups.ResultsFor the 23 patients, high-quality plans could be achieved for target volume and for other organs at risk (OARs). For PTV2, the V107% was 0% and the Dmax did not exceed 106.2% of the prescribed dose. The volume PTV2RU covered by 95% of the dose ranged from 96.16 to 99.95%. The conformality index for PTV2RU was 1.12 ± 0.057 and the homogeneity index (HI) was 1.04 ± 0.014. Rectum Dmax and rectal volume receiving 73–50 Gy could be further reduced for the spacer-group. Significant reductions in mean and median rectal NTCPs (stenosis/necrosis, late rectal bleeding ≥ 2, and late rectal toxicities ≥ 3) were predicted for the spacer group in comparison to the non-spacer group.ConclusionHypofractionated/dose escalated radiotherapy with SIB-IMPT is dosimetrically feasible. Further reduction of the rectal volumes receiving high and medium dose levels (73–50 Gy) and rectal NTCP could be achieved through injection of spacers between rectum and prostate.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation

BackgroundDue to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. MethodsWe retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. Results17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. ConclusionsRobustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Intensity Modulated Proton Beam Therapy versus Volumetric Modulated Arc Therapy for Patients with Nasopharyngeal Cancer: A Propensity Score-Matched Study.

Simple SummaryBased on literature evidence, it is difficult to conclude the advantages and safety of IMPT in patients with NPC. We performed propensity score matching analysis of patients treated with IMPT and VMAT by the same group of physicians within the same institute. Finally, we observed that IMPT reduced the requirement of nasogastric tube insertion and body weight loss during treatment, and the oncologic outcomes were potentially better than that of VMAT. However, IMPT increased the rate of grade III radiation dermatitis. Our current data indicate that IMPT is safe and beneficial as a frontline therapy for patients with NPC.(1) Background: We compared the outcomes of patients with nasopharyngeal carcinoma treated with IMPT and VMAT. (2) Methods: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMPT (years: 2016–2018) and VMAT (2014–2018). Survival was estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis was used to identify the independent predictors of survival. Binary toxicity endpoint analyses were performed using a Cox model and logistic regression. (3) Results: Eighty patients who received IMPT and VMAT were included. The median follow-up time was 24.1 months in the IMPT group. Progression-free survival (PFS) and overall survival (OS) were not statistically different between the two groups but potentially better in IMPT group. In multivariate analysis, advanced N-stage and body weight loss (BWL; >7%) during radiotherapy were associated with decreased PFS. The IMPT group had significantly less requirement for nasogastric (NG) tube placement and BWL during treatment. The mean oral cavity dose was the only predictive factor in stepwise regression analysis, and IMPT required a significantly lower mean dose. However, IMPT increased the grade 3 radiation dermatitis. (4) Conclusions: IMPT is associated with reduced rates of NG tube insertion and BWL through reducing oral mean dose, potentially producing better oncologic outcomes.

Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

PurposeTo investigate potential advantages of adaptive intensity‐modulated proton beam therapy (A‐IMPT) by comparing it to adaptive intensity‐modulated X‐ray therapy (A‐IMXT) for nasopharyngeal carcinomas (NPC).MethodsTen patients with NPC treated with A‐IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A‐IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A‐IMXT with A‐IMPT.ResultsThe means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A‐IMPT are lower than those of A‐IMXT, with statistical significance. The means of, D0.03cc, and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A‐IMPT are significantly lower than those of A‐IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1).ConclusionsAn adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.

Intensity Modulated Proton Beam Therapy (IMPT) in CNS and Skull Base Tumors: Prospective Data of 50 Patients With Early Clinical Follow-Up And Patient Reported Outcomes

Intensity Modulated Proton Beam Therapy (IMPT) in CNS and Skull Base Tumors: Prospective Data of 50 Patients With Early Clinical Follow-Up And Patient Reported Outcomes

Introduction of Image‑Guided Pencil Beam for Skull Base Tumors in India: A Report of Two Cases and a Brief Review of the Literature.

Chordoma and chondrosarcoma are locally aggressive tumors occurring in one-third cases at the base of the skull. These tumors often recur locally with significant morbidity and mortality. The mainstay of treatment is maximal safe tumor debulking. However, in spite of gross total resection, these tumors are likely to recur. Hence, adjuvant radiation is provided to reduce the risk of local recurrence and to improve outcomes. These tumors are considered relatively radioresistant; hence, high doses of radiation are generally required during treatment. However, the presence of several important structures around the lesion poses a major challenge with respect to covering the target with the prescribed high dose. In this regard, protons, for their physical and dosimetric advantages, have become the accepted modality of treatment in these tumors. With the evolution of proton beam therapy (PBT) over the years, especially pencil beam scanning techniques; which result in an extremely high conformal intensity-modulated proton beam therapy (IMPT), robust and Monte Carlo optimization, computational algorithms, and biological modelling are the significant advances which have further enhanced the value of this technology and have improved outcomes. Herein, we would like to report our experience of two cases of skull base tumors treated with intensity-modulated proton therapy at our center along with a review of the literature.

Automation of routine elements for spot-scanning proton patient-specific quality assurance.

At our institution, all proton patient plans undergo patient-specific quality assurance (PSQA) prior to treatment delivery. For intensity-modulated proton beam therapy, quality assurance is complex and time consuming, and it may involve multiple measurements per field. We reviewed our PSQA workflow and identified the steps that could be automated and developed solutions to improve efficiency. We used the treatment planning system's (TPS) capability to support C# scripts to develop an Eclipse scripting application programming interface (ESAPI) script and automate the preparation of the verification phantom plan for measurements. A local area network (LAN) connection between our measurement equipment and shared database was established to facilitate equipment control, measurement data transfer, and storage. To improve the analysis of the measurement data, a Python script was developed to automatically perform a 2D-3D γ-index analysis comparing measurements in the plane of a two-dimensional detector array with TPS predictions in a water phantom for each acquired measurement. Device connection via LAN granted immediate access to the plan and measurement information for downstream analysis using an online software suite. Automated scripts applied to verification plans reduced time from preparation steps by at least 50%; time reduction from automating γ-index analysis was even more pronounced, dropping by a factor of 10. On average, we observed an overall time savings of 55% in completion of the PSQA per patient plan. The automation of the routine tasks in the PSQA workflow significantly reduced the time required per patient, reduced user fatigue, and frees up system users from routine and repetitive workflow steps allowing increased focus on evaluating key quality metrics.

Adopting Advanced Radiotherapy Techniques in the Treatment of Paediatric Extracranial Malignancies: Challenges and Future Directions

Geometric uncertainties in radiotherapy are conventionally addressed by defining a safety margin around the radiotherapy target. Misappropriation of such margins could result in disease recurrence from geometric miss or unnecessary irradiation of normal tissue. Numerous quantitative organ motion studies in adults have been published, but the first paediatric-specific studies were only published in recent years. In the very near future, intensity-modulated proton beam therapy and magnetic resonance-guided radiotherapy will be clinically implemented in the UK. Such techniques offer the ability to deliver radiotherapy to the pinnacle of precision and accuracy, if geometric uncertainty relating to internal organ motion and deformation can be optimally managed. The optimal margin to account for internal organ motion in children remains largely undefined. Continuing efforts to characterise motion in children and young people is necessary to optimally define safety margins and to realise the full potential of intensity-modulated radiotherapy, magnetic resonance-guided radiotherapy and intensity-modulated proton beam therapy. This overview offers a timely review of published reports on paediatric organ motion, in anticipation of the increasing application of advanced radiotherapy techniques in paediatric radiotherapy.

SY5-3 - Role of radiotherapy for multidisciplinary treatment of head and neck cancer

Definitive radiotherapy (RT) plays an essential role for locally advanced head and neck cancer (LAHNC), especially for organ preservation. Although RT can show clear benefit in minimal invasive therapy regarding both organ preservation and better patient's QOL, the tumor control of LAHNC was insufficient. Thus, multidisciplinary approach was required in improving efficacy of definitive RT. Concurrent chemoradiotherapy (CCRT) with platinum agents was believed as standard modality because of improving tumor control, while increasing radiation morbidity sometimes became significant problems. Even if CCRT was administered, local failure still remained essential problem for LAHNC after CCRT, thus, surgical intervention was sometimes needed to salvage either residual or recurrent disease. In addition, postoperative CCRT was reported to be considered for patients with high risk features such as positive surgical margin and/or extranodal extension. More intensive treatment sometimes sacrificed functional and social status of LAHNC patients, so less invasive treatment became one of the major clinical requirement for improving treatment outcome. Recently, intensity modulated radiation therapy (IMRT) has been penetrated to Japanese clinical practice for LAHNC. Using this technique, conformal dose distribution to both tumor and microscopic tumor burden could be achieved with sufficient dose-sparing to the normal tissue. Thus, IMRT could allow to minimize late radiation morbidity, especially for xerostomia without sacrificing treatment efficacy. IMRT is believed to useful modality for LAHNC at both definitive and adjuvant setting. More sophisticated IMRT technique would be expected to reduce dose exposure to the normal organ. Furthermore, intensity modulated proton beam therapy could reach to the further improvement of treatment quality with its physical superiority in dose distribution. Prospective trial using these high-precision RT techniques will be warranted.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus Proton Therapy for Oropharyngeal Squamous Cell Carcinoma

Tocompared the cost-effectiveness of intensity modulated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in the management of stage III-IVB oropharynx cancer (OPC). A Markov model was constructed to compare IMRT with PBT for a 65-year-old patient with stage IVA OPSCC. We assumed PBT led to a 25% reduction in long-term xerostomia, short-term dysgeusia, and the need for gastrostomy tube. Fewer dental complications were also expected with PBT. Incremental cost-effectiveness ratios (ICERs) were calculated, and value of information analyses were performed. The societal willingness-to-pay was defined as $100K per quality-adjusted life year (QALY). The ICERs for PBT for favorable human papillomavirus (HPV)-positive OPC were $288,000/QALY and $390,000/QALY in the payer perspective (PP) and societal perspective, respectively. Under nearly every scenario, PBT was not cost-effective, with ICERs above $150,000/QALY in the PP. The ICERs for HPV-negative OPC were typically greater than $250K/QALY in both perspectives. For HPV-positive patients, the ICER was less than $100,000/QALY in the PP only in younger patients who experienced a 50% reduction in both xerostomia and gastrostomy use. On probabilistic sensitivity analyses, there were 0% and 0.4% probabilities that PBT was cost-effective for 65- and 55-year old patients, respectively. The value of information was zero or negligible for all ages and perspectives at willingness-to-pay of $100,000/QALY and only meaningful in the PP for younger patients at a willingness-to-pay of $150,000/QALY. Intensity modulated proton beam therapy was only cost-effective in the PP if assumed to achieve profound reductions in long-term morbidity for younger patients; it was never cost-effective in the societal perspective. Prospective data are needed (and may be valuable) to better characterize the comparative toxicities of these treatments but are unlikely to change this calculation, except potentially in the most favorable cohort of patients.

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer – A case matched analysis

BackgroundOwing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities. MethodsWe performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010–2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis. ResultsFifty IMPT and 100 IMRT patients were included. The median follow-up time was 32months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8years for IMRT patients and 61.1years for IMPT patients, p-value=0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR)=0.55; 95% confidence interval (CI): 0.12–2.50, p-value=0.44) or in progression-free survival (HR=1.02; 95% CI: 0.41–2.54; p-value=0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR=0.53; 95% CI: 0.24–1.15; p-value=0.11 and OR=0.43; 95% CI: 0.16–1.17; p-value=0.10 at 3months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR=0.44; 95% CI: 0.19–1.0; p-value=0.05 at 3months after treatment and OR=0.23; 95% CI: 0.07–0.73; p-value=0.01 at 1year after treatment. ConclusionOur results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.