Radiotherapy Target Volume Research Articles

P02.11.B An hypothesis generating study of MRI-Derived Radiomics on tumor and microenvironment tissue heterogeneity to guide post-operative management of glioblastoma: toward personalized radiation treatment volume delineation

Abstract Background The glioblastoma’s bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification.The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigated the role of radiomic analysis in GBM management, to verify if radiomic features in the tissue around the resection cavity which may guide the radiation target volume delineation. Material and Methods We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction.The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologist reviewed by a neuroradiologist, both with at least 10 years of experience. The Region of interest (ROI) considered for the analysis were: the surgical cavity +/- post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modelling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using the 226 features extracted from the Ring to perform a binary classification and predict the PFS at 6 months (statistical, morphological and textural features). A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68 - 0.88). Conclusion This is the first hypothesis-generating study who applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GBM patients in order to achieve a margin reduction strategy.

Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer.

We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.

Radiotherapy Target Volume Definition in Newly Diagnosed High-Grade Glioma Using 18F-FET PET Imaging and Multiparametric MRI: An Inter Observer Agreement Study.

Background: The aim of this prospective monocentric study was to assess the inter-observer agreement for tumor volume delineations by multiparametric MRI and 18-F-FET-PET/CT in newly diagnosed, untreated high-grade glioma (HGG) patients. Methods: Thirty patients HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine(18F-FET) positron emission tomography (PET), and multiparametric MRI with computation of rCBV map and K2 map. Three nuclear physicians and three radiologists with different levels of experience delineated the 18-F-FET-PET/CT and 6 MRI sequences, respectively. Spatial similarity (Dice and Jaccard: DSC and JSC) and overlap (Overlap: OV) coefficients were calculated between the readers for each sequence. Results: DSC, JSC, and OV were high for 18F-FET PET/CT, T1-GD, and T2-FLAIR (>0.67). The Spearman correlation coefficient between readers was ≥0.6 for these sequences. Cross-comparison of similarity and overlap parameters showed significant differences for DSC and JSC between 18F-FET PET/CT and T2-FLAIR and for JSC between 18F-FET PET/CT and T1-GD with higher values for 18F-FET PET/CT. No significant difference was found between T1-GD and T2-FLAIR. rCBV, K2, b1000, and ADC showed correlation coefficients between readers <0.6. Conclusion: The interobserver agreements for tumor volume delineations were high for 18-F-FET-PET/CT, T1-GD, and T2-FLAIR. The DWI (b1000, ADC), rCBV, and K2-based sequences, as performed, did not seem sufficiently reproducible to be used in daily practice.

Validation of four-dimensional computed tomography without external reference respiratory signals for radiation treatment planning of lung tumors

Deviceless four-dimensional (4D) computed tomography (CT) allows the acquisition of respiratory signals from six features without requiring an external device for cine CT processing. This method has been recently introduced in radiation treatment planning of lung tumors. To validate deviceless 4D CT, it must be compared with conventional 4D CT, which requires an external monitoring device. We compared the two methods using a multicell 4D phantom that simulates patient’s movement during respiration regarding the target volume (TV), target position (TP), and internal TV for lung tumor radiation therapy. We retrospectively obtained images of 10 patients who underwent radiation treatment planning of lung tumors and compared the two methods, as in the phantom study. For the phantom study, the mean TV, root mean square errors of the TP, and mean internal TV differences between the two methods ranged from −4.5% to 1.2%, 0.7 to 2.6 mm, and −1.1% to 3.4%, respectively. The corresponding results of the clinical study ranged from −1.5% to 14.9%, 0.1 to 5.9 mm, and −9.7% to 10.1%, respectively. The results of deviceless 4D CT for the clinical study were consistent with those of conventional 4D CT, except for target movements with high excursions. Therefore, deviceless 4D CT can be an alternative to conventional 4D CT for radiation treatment planning of lung tumors.

Erring Characteristics of Deformable Image Registration-Based Auto-Propagation for Internal Target Volume in Radiotherapy of Locally Advanced Non-Small Cell Lung Cancer.

PurposeRespiratory motion of locally advanced non-small cell lung cancer (LA-NSCLC) adds to the challenge of targeting the disease with radiotherapy (RT). One technique used frequently to alleviate this challenge is an internal gross tumor volume (IGTV) generated from manual contours on a single respiratory phase of the 4DCT via the aid of deformable image registration (DIR)-based auto-propagation. Through assessing the accuracy of DIR-based auto-propagation for generating IGTVs, this study aimed to identify erring characteristics associated with the process to enhance RT targeting in LA-NSCLC.Methods4DCTs of 19 patients with LA-NSCLC were acquired using retrospective gating with 10 respiratory phases (RPs). Ground-truth IGTVs (GT-IGTVs) were obtained through manual segmentation and union of gross tumor volumes (GTVs) in all 10 phases. IGTV auto-propagation was carried out using two distinct DIR algorithms for the manually contoured GTV from each of the 10 phases, resulting in 10 separate IGTVs for each patient per each algorithm. Differences between the auto-propagated IGTVs (AP-IGTVs) and their corresponding GT-IGTVs were assessed using Dice coefficient (DICE), maximum symmetric surface distance (MSSD), average symmetric surface distance (ASSD), and percent volume difference (PVD) and further examined in relation to anatomical tumor location, RP, and deformation index (DI) that measures the degree of deformation during auto-propagation. Furthermore, dosimetric implications due to the analyzed differences between the AP-IGTVs and GT-IGTVs were assessed.ResultsFindings were largely consistent between the two algorithms: DICE, MSSD, ASSD, and PVD showed no significant differences between the 10 RPs used for propagation (Kruskal–Wallis test, ps > 0.90); MSSD and ASSD differed significantly by tumor location in the central–peripheral and superior–inferior dimensions (ps < 0.0001) while only in the central–peripheral dimension for PVD (p < 0.001); DICE, MSSD, and ASSD significantly correlated with the DI (Spearman’s rank correlation test, ps < 0.0001). Dosimetric assessment demonstrated that 79% of the radiotherapy plans created by targeting planning target volumes (PTVs) derived from the AP-IGTVs failed prescription constraints for their corresponding ground-truth PTVs.ConclusionIn LA-NSCLC, errors in DIR-based IGTV propagation present to varying degrees and manifest dependences on DI and anatomical tumor location, indicating the need for personalized consideration in designing RT internal target volume.

A measure tool for evaluating dose falloff outside the target volume in high precision radiotherapy

IntroductionA reliable and high resolution systemic with all aspects plan evaluation indices has been proposed in this study to measure the dose falloff outside the target volume. The essential goal of this study is to compensate the shortcomings for the judgment of planning target volume and dose-volume histogram by visual verification slice by slice in high precision modern radiotherapy techniques like stereotactic radiation surgery, volumetric arc therapy, and stereotactic body radiation therapy. Materials and methodsDynamic Gradient Index has been proposed both geometric and dosimetric orientated in all aspects plan evaluation indices to measure the dose falloff outside the target volume. Organ at Risk Integral Dose, and Target Specific Gain Ratio are created for evaluating highly conformal plans and provide better sparing of normal tissue. Users can do the plan evaluation indices calculation proposed in this study just simply with a sequence of exported data including normal tissue volume covered by every isodose line, target volume covered by every isodose line, and organ at risk volume covered by every isodose line from the approved planning system. The results here were also compared with several indices usually used such as gradient index developed by various authors. ResultsDGI avoids the mistaken judgment counted on a single gradient index on one referenced isodose line recommended by other published results for the evaluation of SRS, SBRT high precision needed plan. Dynamic Gradient Index is a measure of steep dose gradient outside the target volume; therefore; this index plays a significant role in SRS as a measure of plan quality, especially a judgment of complication cases. Furthermore, taking into consideration the Organ at Risk Integral Dose and normal tissue integral dose to evaluate the target therapeutic gain lets Target Specific Gain Ratio becomes a comprehensive evaluation tool for pros and cons tangled cases. ConclusionsThe function of DGI successfully reflects the advantage of fast expanded isodose lines (low dose gradient) could be easily examined. The plan superiority is determined by how close the DGI and the other indices are to the line of the benchmark. The growing speed of DGI for the SRS curve is slower similar to VMAT than the other two treatment techniques. The DGI of SRS beyond 100% inside the target area shows the advantage of the plateau between 100% and 110%, which means the change of dose gradient is smaller and this phenomenon could not be checked in DVH as well in other plan evaluation indices.

Intraindividual Comparison Between [18F] PSMA-1007 PET/CT and Multiparametric MRI for Radiotherapy Planning in Primary Prostate Cancer Patients.

IntroductionAccurate detection and segmentation of the intraprostatic gross tumor volume (GTV) is pivotal for radiotherapy (RT) in primary prostate cancer (PCa) since it influences focal therapy target volumes and the patients’ cT stage. The study aimed to compare the performance of multiparametric resonance imaging (mpMRI) with [18F] PSMA-1007 positron emission tomography (PET) for intraprostatic GTV detection as well as delineation and to evaluate their respective influence on RT concepts.Materials and MethodsIn total, 93 patients from two German University Hospitals with [18F] PSMA-1007-PET/CT and MRI (Freiburg) or [18F] PSMA-1007-PET/MRI (Dresden) were retrospectively enrolled. Validated contouring techniques were applied for GTV-PET and -MRI segmentation. Absolute tumor volume and cT status were determined for each imaging method. The PCa distribution from histopathological reports based on biopsy cores and surgery specimen was used as reference in terms of laterality (unilateral vs. bilateral).ResultsIn the Freiburg cohort (n = 84), mpMRI and PET detected in median 2 (range: 1–5) and 3 (range: 1–8) GTVs, respectively (p < 0.01). The median GTV-MRI was significantly smaller than the GTV-PET, measuring 2.05 vs. 3.65 ml (p = 0.0005). PET had a statistically significant higher concordance in laterality with surgery specimen compared to mpMRI (p = 0.04) and biopsy (p < 0.01), respectively. PSMA PET led to more cT2c and cT3b stages, whereas cT3a stage was more pronounced in mpMRI. Based on the cT stage derived from mpMRI and PET information, 21 and 23 as well as 59 and 60 patients, respectively, were intermediate- and high-risk according to the National Comprehensive Cancer Network (NCCN) v1.2022 criteria. In the Dresden cohort (n = 9), similar results were observed.ConclusionIntraprostatic GTV segmentation based on [18F] PSMA-1007 PET results in more and larger GTVs compared to mpMRI. This influences focal RT target volumes and cT stage definition, but not the NCCN risk group.

"Radiation Therapy (RT) Target Volume Determination for Locally Advanced Pyriform Sinus Carcinoma: An Original Research Article Revisiting the Role of Multimodality Imaging"

"Radiation Therapy (RT) Target Volume Determination for Locally Advanced Pyriform Sinus Carcinoma: An Original Research Article Revisiting the Role of Multimodality Imaging"

Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy

BackgroundGallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy.MethodsRetrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis.ResultsThe median follow-up time is 34 months (IQR: 11–64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis.ConclusionThe recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.

RONC-16. Proton therapy for patients with embryonal tumor with multilayered rosettes in early childhood – results of the prospective KiProReg Study

Abstract OBJECTIVES: Embryonal tumors with multilayered rosettes (ETMR) are rare malignancies of the central nervous system occurring predominantly in early childhood. Little is known about optimal time point and target volume of radiotherapy for the respective patients. The aim of this analysis was to evaluate treatment outcome in pediatric patients with ETMR treated with Proton Therapy (PT). METHODS: Between May 2016 and August 2021, 15 patients (9 male /6 female) with ETMR received PT in our institution and were enrolled in the prospective registry study KiProReg. Patient characteristics, treatment and outcome according to standardized follow-up data were descriptively analyzed by summarizing frequencies due to small sample size. RESULTS: Median age at PT was 3.0 years (range, 1.6-4.0 years). Three patients presented with metastatic disease (M1 n=1; M2 n=1; M2/3 n=1). Eight patients were treated with salvage PT at tumor progression or recurrence. Residual disease was present in three patients at start of PT. Tumor site was infratentorial (n=3) or supratentorial (n=12). All patients received Chemotherapy (CTX) prior to PT including high dose CTX (n=9) and intrathecal CTX (n=3). Concomitant CTX with temozolomide was administered in one patient. Patients received local PT (n=8) or craniospinal irradiation (CSI) followed by a local boost (n=7). Median dose was 54.0 Gy(RBE) (range, 3.6 -59.4 Gy(RBE)). PT was terminated prematurely in one patient due to cerebral edema and disease progression. Median follow-up after diagnosis was 16.3 months (range, 6.6-65.7 months) and 5.1 months (range, 0-62.4 months) after PT. Four patients treated for salvage experienced disease progression within three months after PT, three of them deceased. CONCLUSION: Preliminary results suggest promising outcomes for childhood ETMR after PT, especially in patients treated at initial diagnosis. Longer follow-up and larger cohorts are desirable to assess long-term survival and necessity of CSI.

Incidence and extent of disease progression on MRI between surgery and initiation of radiotherapy in glioblastoma patients.

A post-operative MRI (MRIpost-op) performed within 72 h is routinely used for radiation treatment planning in glioblastoma (GBM) patients, with radiotherapy starting about 4-6 weeks after surgery. Some patients undergo an additional pre-radiotherapy MRI (MRIpre-RT) about 2-6 weeks after surgery. We sought to analyze the incidence of rapid early progression (REP) between surgery and initiation of radiotherapy seen on MRIpre-RT and the impact on radiation target volumes. Patients with GBM diagnosed between 2018 and 2020 who had an MRIpost-op and MRIpre-RT were retrospectively identified. Criteria for REP was based on Modified RANO criteria. Radiation target volumes were created and compared using the MRIpost-op and MRIpre-RT. Fifty patients met inclusion criteria. The median time between MRIpost-op and MRIpre-RT was 26 days. Indications for MRIpre-RT included clinical trial enrollment in 41/50 (82%), new symptoms in 5/50 (10%), and unspecified in 4/50 (8%). REP was identified in 35/50 (70%) of patients; 9/35 (26%) had disease progression outside of the MRIpost-op-based high dose treatment volumes. Treatment planning with MRIpost-op yielded a median undertreatment of 27.1% of enhancing disease and 11.2% of surrounding subclinical disease seen on MRIpre-RT. Patients without REP had a 38% median volume reduction of uninvolved brain if target volumes were planned with MRIpre-RT. Given the incidence of REP and its impact on treatment volumes, we recommend using MRIpre-RT for radiation treatment planning to improve coverage of gross and subclinical disease, allow for early identification of REP, and decrease radiation treatment volumes in patients without REP.

A Randomised Phase II Clinical Trial Comparing the Deliverability and Acute Toxicity of Wide Tangent versus Volumetric Modulated Arc Therapy to the Breast and Internal Mammary Chain

AimsInclusion of the internal mammary chain in the radiotherapy target volume (IMC-RT) improves disease-free and overall survival in higher risk breast cancer patients, but increases radiation doses to heart and lungs. Dosimetric data show that either modified wide-tangential fields (WT) or volumetric modulated arc therapy (VMAT) together with [AQ1]voluntary deep inspiration breath hold (vDIBH) keep mean heart doses below 4 Gy in most patients. However, the impact on departmental resources has not yet been documented. This phase II clinical trial compared the time taken to deliver IMC-RT using either WT and vDIBH or VMAT and vDIBH, together with planning time, dosimetry, set-up reproducibility and toxicity. Materials and methodsLeft-sided breast cancer patients requiring IMC-RT were randomised to receive either WT(vDIBH) or VMAT radiotherapy. The primary outcome was treatment time, powered to detect a minimum difference of 75 min (5 min/fraction) between techniques. The population mean displacement, systematic error and random error for cone beam computed tomography chest wall matches in three directions of movement were calculated. Target volume and organ at risk doses were compared between groups. Side-effects, including skin (Radiation Therapy Oncology Group), lung and oesophageal toxicity (Common Terminology Criteria for Adverse Events v 4.03) rates, were compared between the groups over 3 months. Patient-reported outcome measures, including shoulder toxicity at baseline, 6 months and 1 year, were compared. ResultsTwenty-one patients were recruited from a single UK centre between February 2017 and January 2018. The mean (standard deviation) total treatment time per fraction for VMAT treatments was 13.2 min (1.7 min) compared with 28.1 min (3.3 min) for WT(vDIBH). There were no statistically significant differences in patient set-up errors in between groups. The average mean heart dose for WT(vDIBH) was 2.6 Gy compared with 3.4 Gy for VMAT(vDIBH) (P = 0.13). The mean ipsilateral lung V17Gy was 32.8% in the WT(vDIBH) group versus 34.4% in the VMAT group (P = 0.2). The humeral head (mean dose 16.8 Gy versus 2.8 Gy), oesophagus (maximum dose 37.3 Gy versus 20.1 Gy) and thyroid (mean dose 22.0 Gy versus 11.2 Gy) all received a statistically significantly higher dose in the VMAT group. There were no statistically significant differences in skin, lung or oesophageal toxicity within 3 months of treatment. Patient-reported outcomes of shoulder toxicity, pain, fatigue, breathlessness and breast symptoms were similar between groups at 1 year. ConclusionVMAT(vDIBH) and WT(vDIBH) are feasible options for locoregional breast radiotherapy including the IMC. VMAT improves nodal coverage and delivers treatment more quickly, resulting in less breath holds for the patient. This is at the cost of increased dose to some non-target tissues. The latter does not appear to translate into increased toxicity in this small study.

Safety and potential increased risk of toxicity of radiotherapy combined immunotherapy strategy.

Accumulating interest has emerged in exploring the toxicity profiles of the combination strategy of radiotherapy (RT) and immune checkpoint inhibitors (ICIs). Much remains unknown regarding safety and the potential increased risk of toxicity of acombined treatment. ICI prolongs survival but can induce immune-related adverse events as well. To increase awareness of adverse effect and support immediate and successful management, we go over the literature on the safety of RT combined immunotherapy strategy. Representative evidence relevant to RT combined with ICI in the brain, lung, head and neck, and pelvic malignance was reviewed respectively. Given radiation doses and fractionation, the irradiated volume, the timing of RT, and ICI would significantly affect the safety and efficiency of ICI+RT combination therapy, and no consensus had been reached about how to arrange RT delivery in the combined contexture, we went over the available literature and tried to address these challenges including the timing of RT, optimal dose and fractionations, RT target and target volume, and potential biomarkers to predict toxicity. We found even though RT+ICI combination therapy might augment toxicities, the majority of patients experienced grade 4 or 5 AE are relatively rare and no significant difference could be found between combination group and monotherapy group. Sometimes the acute toxicity with ICI is much less predictable and often life threatening and in some can give rise to permanent effects. Clinicians across disciplines should be aware of these uncommon lethal complications induced by ICI+RT. Early recognition is the key to successful treatment, reversibility of organ dysfunction, and in some cases even prevention of fatal outcome. If recognized early, managed properly, and no fatal AE occurs, the development of irAE indicates a good prognosis. It should be noted that nothing is known about potential late effects because very few studies have 5-year follow-up. The nature of irAE is the attack of activated immune cells on normal tissues. The nature of RT-induced AE is the DNA damage on normal tissue, which is related with the dose delivered and volume irradiated and the tolerance of surrounding normal tissues. The immune-modulating effect of SBRT may augment the damage on normal tissues. To maximize the antitumor immune response, 8-12Gy/fraction is preferred when conducting RT. The available clinical evidence suggest RT of this dose/fractionated strategy combined with ICI have a tolerable AE profile, which need further validation by more clinical trials in the future. The combination strategy of RT with anti-PD1/PDL1 anti-body is supposed to be concurrent or RT followed by anti-PD1/PDL1 antibody. Although RT and ipilimumab combination sequence is controversial, ipilimumab prior to or concurrent with RT might be proper, which need more clinical validation. Under the concept of immunological dose painting, SBRT work as a trigger of immune response. It has been observed that SBRT of partially radiated tumors combined with ICI could induce similar tumor control compared with total tumor irradiation. The side effects of RT may be mitigated potentially due to the reduction of irradiated volume. The antitumor efficiency and safety profile of immunological RT dose painting+ICI deserve further investigation. Clinical predictive factors for irAE risk remain unclear, and more investigation deserves to be conducted about the irAE prediction.

Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review.

Simple SummaryAs radical radiation therapy for non-small-cell lung cancer becomes increasingly precise following the development of techniques such as image-guided radiotherapy and intensity-modulated radiotherapy, how we define the clinical target volume (CTV) is crucial. Although assessing the scope of microscopic extension and microscopic proximal bronchial extension from the primary tumor is critical for defining the CTV, there is currently no consensus on this issue. Accordingly, we conducted this systematic review with the aim of assessing the available evidence. Although there were few studies with a high level of evidence, this systematic review enabled us to collate the available results and to provide some recommendations regarding suitable CTV margins.A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the CTV, there has been limited research on ME and PBE. Therefore, we conducted this systematic review. The PubMed, ICHUSHI (Japanese database), and Cochrane Library databases were searched, and 816 articles were initially retrieved. After primary and secondary screenings, eight articles were ultimately selected. The results of this systematic review suggest the importance of a 0 mm margin in stereotactic radiotherapy for early-stage cancer and a 5–8 mm margin in curative irradiation for locally advanced cancer. Regarding PBE, this review yielded the conclusion that it is appropriate to consider the addition of an approximately 15 mm margin from the bronchial vasculature. Although there were few articles with a high level of evidence, this systematic review enabled us to collate results from previous studies and to provide recommendations, to some extent, regarding the CTV margin in the current clinical environment, where high-precision radiation therapy, such as image-guided radiotherapy and intensity-modulated radiotherapy, is predominant.

Multimodality imaging based treatment volume definition for recurrent Rhabdomyosarcomas of the head and neck region: An original article

Objective: Rhabdomyosarcomas are among the malignant soft tissue tumors which may originate from primitive mesenchymal cells. These tumors may also be located in the head and neck region and may behave locally aggressive with the invasion of nearby structures. Radiation therapy (RT) may play a role as part of initial management as adjunctive therapy, or for treatment of recurrent disease. Accuracy and precision in RT treatment volume definition have gained utmost importance for achieving optimal treatment results. Herein, we assess multimodality imaging-based RT treatment volume definition for irradiation of recurrent head and neck rhabdomyosarcomas. Materials and methods: Multimodality imaging-based RT treatment volume definition for irradiation of recurrent head and neck rhabdomyosarcomas were evaluated in this study. RT target volume definition by incorporation of magnetic resonance imaging (MRI) or by computed tomography (CT)-simulation images only was assessed with comparative analysis for patients receiving RT for recurrent head and neck rhabdomyosarcomas. Results: As the main outcome of this study, ground truth target volume has been found to be identical to treatment volume definition by CT-MR fusion-based imaging. Conclusion: Optimal management of recurrent head and neck rhabdomyosarcomas may be improved by precise and accurate RT treatment volume determination. Within this context, the incorporation of MRI in the target and treatment volume definition process may be strongly recommended to achieve improved accuracy and precision in target and treatment volume determination despite the need for further supporting evidence.

PD-0403 Assessment of residual setup errors of clinical target volumes for head and neck radiotherapy

PD-0403 Assessment of residual setup errors of clinical target volumes for head and neck radiotherapy

Clinical evaluation of a deep learning model for segmentation of target volumes in breast cancer radiotherapy

Purpose/Objective(s)Precise segmentation of clinical target volumes (CTV) in breast cancer is indispensable for state-of-the art radiotherapy. Despite international guidelines, significant intra- and interobserver variability exists, negatively impacting treatment outcomes. The aim of this study is to evaluate the performance and efficiency of segmentation of CTVs in planning CT images of breast cancer patients using a 3D convolutional neural network (CNN) compared to the manual process. Materials/MethodsAn expert radiation oncologist (RO) segmented all CTVs separately according to international guidelines in 150 breast cancer patients. This data was used to create, train and validate a 3D CNN. The network’s performance was additionally evaluated in a test set of 20 patients. Primary endpoints are quantitative and qualitative analysis of the segmentation data generated by the CNN for each level specifically as well as for the total PTV to be irradiated. The secondary endpoint is the evaluation of time efficiency. ResultsIn the test set, segmentation performance was best for the contralateral breast and the breast CTV and worst for Rotter’s space and the internal mammary nodal (IMN) level. Analysis of impact on PTV resulted in non-significant over-segmentation of the primary PTV and significant under-segmentation of the nodal PTV, resulting in slight variations of overlap with OARs. Guideline consistency improved from 77.14% to 90.71% in favor of CNN segmentation while saving on average 24 minutes per patient with a median time of 35 minutes for pure manual segmentation. Conclusion3D CNN based delineation for breast cancer radiotherapy is feasible and performant, as scored by quantitative and qualitative metrics.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Rectal Cancer: Long-Term Results after Protocol-Based Treatment.

Background Volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) is an advanced form of radiotherapy (RT) technology. The purpose of this study was to report long-term treatment outcomes in patients with locally advanced rectal cancer undergoing VMAT-SIB based concurrent chemoradiotherapy (CRT). Methods Between January 2016 and January 2018, a total of 22 patients with operable stage II-III rectal adenocarcinoma were recruited for the pre-designed VMAT-SIB RT protocol. All patients underwent standard diagnostic and staging work-up. The RT target volumes included the following areas: PTV1 = mesorectum that contained gross tumors and enlarged lymph node regions and PTV2 = mesorectum and regional lymphatics from L4-5/S1 to 3-4 cm below the tumor or levator ani muscle, excluding PTV1. The VMAT-SIB dose prescription was as follows: PTV1 = 52.5 Gy/daily 2.1 Gy/25 fractions, PTV2 = 45 Gy/daily 1.8 Gy/25 fractions. Results The mean age of the study population was 64 (range, 18-84) years, and 15 (68.2%) patients were male. Radical operation (total mesorectal excision) was performed by either low anterior resection, ultralow anterior resection, or abdominal perineal resection. All five (22.7%) of the patients with confirmed increasing serum carcinoembryonic antigen (CEA) level at diagnosis showed normalization of serum CEA level after the planned treatment. Among 20 patients who underwent preoperative CRT and surgery, tumor down staging in T- and N-stages was achieved in 10 patients (50%) and 13 patients (65%), respectively, with 20% of ypT0/Tis. With a median follow-up of 54.2 (range, 22.6-61.1) months, the 5-year disease-free survival, overall survival, and local control rates were 64.6%, 81.8%, and 84.4%, respectively. Five patients developed distant metastasis and one developed local recurrence as a first event. Two cases with anastomosis site leakage, three with adhesive ileus, and two with abscess formation were observed during postoperative periods. Conclusions The current VMAT-SIB-based CRT protocol provided acceptable treatment and toxicity outcomes.

Ectopic Recurrence of Skull Base Chordoma after Proton Therapy.

Simple SummaryChordoma are very rare tumors of the spine and skull base. Due to close proximity of crucial organs, like the brain stem, complete removal can often not be achieved, and tumor tissue, either macroscopic or microscopic, remains in situ. Local recurrence up to 88% occurs in 10 years. Ectopic recurrence as an early sign of treatment failure is considered rare. We retrospectively reviewed five patients with ectopic recurrence as a first sign of treatment failure after treatment with surgery and proton therapy, and studied the applied treatment strategies and imaging follow-up. We found 18 ectopic recurrences in these five patients, of which 17 (94%) could be related to prior surgical tracts. Our theory is that these relapses occur due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival.Background: Chordoma are rare tumors of the axial skeleton. The treatment gold standard is surgery, followed by particle radiotherapy. Total resection is usually not achievable in skull base chordoma (SBC) and high recurrence rates are reported. Ectopic recurrence as a first sign of treatment failure is considered rare. Favorable sites of these ectopic recurrences remain unknown. Methods: Five out of 16 SBC patients treated with proton therapy and surgical resection developed ectopic recurrence as a first sign of treatment failure were critically analyzed regarding prior surgery, radiotherapy, and recurrences at follow-up imaging. Results: Eighteen recurrences were defined in five patients. A total of 31 surgeries were performed for primary tumors and recurrences. Seventeen out of eighteen (94%) ectopic recurrences could be related to prior surgical tracts, outside the therapeutic radiation dose. Follow-up imaging showed that tumor recurrence was difficult to distinguish from radiation necrosis and anatomical changes due to surgery. Conclusions: In our cohort, we found uncommon ectopic recurrences in the surgical tract. Our theory is that these recurrences are due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival.

Reappraisal of multimodality imaging for improved Radiation Therapy (RT) target volume determination of recurrent Oral Squamous Cell Carcinoma (OSCC): An original article

Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most frequent cancer sites around the globe. Within the heterogeneous group of HNSCC, Oral Squamous Cell Carcinoma (OSCC) deserves the utmost attention as an important subsite. Despite multimodality management, recurrence of OSCC is not uncommon. RT may play an integral role as part of initial management or as adjunctive therapy, or for treatment of recurrent disease. In this study, we evaluate multimodality imaging-based RT treatment volume definition for irradiation of recurrent OSCC. Materials and methods: Multimodality imaging-based RT treatment volume definition for radiotherapeutic management of recurrent OSCC was assessed. RT target volume determination by incorporation of Magnetic Resonance Imaging (MRI) or by Computed Tomography (CT)-simulation images only has been evaluated and comparative analysis has been performed for patients receiving salvage RT for recurrent OSCC. Results: Ground truth target volume has been found to be identical with treatment volume definition by CT-MR fusion-based imaging. Conclusion: Incorporation of MRI in target and treatment volume definition may improve target and treatment volume definition for recurrent OSCC.