Nodal Volume Research Articles

An integrated topology optimization method including manufacturing constraints for 3D printed fiber-reinforced concrete structures

The difficulty of achieving overall optimization design of concrete materials, structures, and performances has always been a bottleneck restricting the safety and comprehensive performance improvement of civil engineering structures throughout their life cycle. Driven by digital design, 3D concrete printing (3DCP) with a high degree of freedom and flexibility can achieve accurate distribution of materials and flexible construction, which is a favorable guarantee for the high-quality construction of high-performance structures. In this paper, an integrated design method of material-process-performance is developed by introducing both concrete material properties and printing process parameters into the optimization design. The nodal volume fraction and material orientation are selected as design variables to obtain lightweight structures, meanwhile the tensile capacity enhanced through fiber alignment is fully utilized. The minimum size control combined with the central axis algorithm is introduced to achieve integer multiple of nozzle size and also to improve the manufacturing quality. Structural compliance and stress are adopted as the objective function and constraint to improve structural stiffness and strength, respectively. Test results show that the strength-to-weight ratio of the optimized beam is 42 % higher than that of the cast-in-place one, and therefore the effectiveness of the proposed method is validated.

Dose planning study of proton versus photon radiotherapy for head and neck squamous cell carcinoma of unknown primary in the primary and recurrent setting

Background Patients with head and neck squamous cell carcinoma of unknown primary (HNCUP) are often treated with extensive radiotherapy (RT). Frequently, the bilateral nodal clinical target volume (nCTV) and the volumes of suspected mucosal primary sites (mCTV) of the pharynx and larynx is irradiated. This treatment is effective but toxic. New data suggest that omission of the contralateral nCTV and mCTV, results in few recurrences. The present study explores photon versus proton therapy, in the primary and recurrent setting. Material and methods An analysis of twelve patients previously treated for HNCUP was performed. A fictitious recurrence was defined in patients treated for unilateral disease. Independently a volumetric arc photon plan and an intensity-modulated proton plan was made for all cases and scenarios. Results Compared to the standard bilateral treatment this study shows that limiting the target to unilateral nCTV leads to a significant decrease in dysphagia of 18% and 17% and xerostomia of 4.0% and 5% for photon and protons, respectively. Comparing photon RT directly to proton RT shows a small and often insignificant gain, using protons for both bilateral and unilateral targets. Focusing on re-irradiation, benefits from using protons in both the primary setting and at re-irradiation were limited. However, using protons for re-irradiation only leads to a decrease in the tissue volume receiving a specific dose outside the target overlapping region, e.g., V90Gymean was 31, 25, and 22 cm3 for photons-photons, photons-protons, and protons-protons, respectively. For V100Gy of the ipsilateral carotid artery, no differences were observed. Conclusion Omitting contralateral nCTV irradiation and mCTV irradiation will significantly reduce toxicity. The accumulated high dose volumes can be minimised using protons for re-irradiation. However, the use of protons for primary treatment provides limited benefit in most patients.

Man vs. Machine (Learning): Comparing Speed and Cost-Effectiveness of Manual vs. Deep Learning Segmentation-Aided Volume Delineation for Head and Neck Lymph Node Targets.

The purposes of the following study were to: 1) compare the time required to delineate head and neck lymph nodal volumes using a manual versus deep learning segmentation (DLS) - aided approach and 2) investigate the potential cost-savings per scan. 10 de-identified head and neck CT simulation datasets were randomly selected for segmentation and analysis. Using published consensus definitions of 27 total lymph node regions1, 1 radiation oncologist manually segmented all 10 CT datasets. For each patient, the time required to contour and review the dataset was recorded. Next, for each dataset, the time required to generate and modify DLS-generated volumes via a proprietary software was recorded, including image export from treatment planning system (TPS), uploading to DLS software, volume generation, downloading volumes, importing volumes into the TPS, and manual edits required. Mean and standard deviations for each treatment modality were calculated. Using two-sided t-test, the statistical difference between the measured outcomes were compared. Finally, assuming a salary of $500,000 per year, average cost savings per scan were calculated. Time required to segment each dataset manually (mean = 59.32 min, SD = 9.16) versus DLS-aided (mean = 14.55 min, SD = 3.16) was statistically significant (p-value = 1.91E-07). Estimated cost required to segment each dataset manually (mean = $237.67, SD = $36.69) versus DLS-aided (mean = $58.27, SD = $12.64) was also statistically significant (p-value = 1.91E-07). The DLS-aided approach resulted in a $179.40 savings per CT dataset segmented, as well as an absolute time savings of 44.78 minutes per scan. This preliminary study shows that using a DLS-aided approach to head and neck lymph node stations can be feasibly implemented within a standard radiation oncology workflow and has the potential for significant time and cost savings.

Clinical Acceptability of Automatically Generated Elective Lymph Node Volumes for Head and Neck Cancer Patients

Manual contouring of head and neck lymph node levels is a time-intensive process prone to provider-specific variation. The purpose of this work is to generate a clinical segmentation tool while minimizing the amount of manual effort required by physicians to develop training datasets and review contours. Here we investigate an approach to curate, develop, and clinically validate an auto-contouring model for standard cervical lymph node volumes in the head and neck using a publicly available deep learning architecture. This model updates our previously validated tool to reflect modern practices in lymph node segmentation. With the assistance of a resident physician, five radiation oncologists manually contoured individual lymph node levels on CT scans for three separate patients treated definitively with radiation or chemoradiation for oropharynx cancer, resulting in 15 unique ground truth cases. These cases were then used to train an nnUnet deep-learning model to generate automated contours for 32 additional cases. These 32 cases were reviewed, manually edited, and used to create the final model. Finally, the model was used to generate contours on the original 15 CT scans (testing cohort), and providers compared these automated contours with the ground-truth (manual) contours. Two blinded studies were performed. In a double-blinded fashion, providers were first asked to select which set of contours they would prefer to use in clinical practice as a starting point for actual cases. Second, they scored each contour on a Likert scale (1-5) to indicate clinical acceptability, ranging from completely unusable to usable without modification. Across all lymph node levels (IA, IB, II, III, IV, V, RP), average Dice Similarity Coefficient ranged from 0.77 to 0.89 for AI vs manual contours in the testing cohort. These AI and manual lymph node contours were reviewed by 5 physicians each, resulting in 525 preference scores. Across all lymph nodes, the AI contour was superior to or equally preferred to the manual contours at rates ranging from 75% to 91% in the first blinded study. In the second blinded study, physician preference for the manual vs AI contour was statistically different for only the RP contours (p < 0.01). Thus, there was not a significant difference in clinical acceptability for nodal levels I-V for manual versus AI contours. Across all physician-generated contours, 82% were rated as usable with stylistic to no edits, and across all AI-generated contours, 92% were rated as usable with stylistic to no edits. An approach to generate clinically acceptable automated contours for cervical lymph node levels in the head and neck was demonstrated. Furthermore, for nodal levels I-V, there was no significant difference in clinical acceptability in manual vs AI contours. Because we were able to generate and validate a model for each lymph node level individually, the output is applicable to a complete range of disease in which cervical lymph nodes are treated.

Dosimetric Comparison of Nodal Clinical Target Volume for Locally Advanced Non-Small Cell Lung Cancer: Options for Geometric Expansion vs. Lymph Node Stations

We investigated whether dosimetric differences existed in nodal clinical target volume (CTV) using options for geometric expansion and lymph node stations based on the European Society for Radiotherapy and Oncology (ESTRO) guideline for locally advanced non-small cell lung cancer (NSCLC). With treatment planning computed tomographic images in 17 patients who underwent radiotherapy for cT4N2M0 NSCLC from 2017 to 2022 at our institution, we retrospectively contoured nodal CTVs based on the guideline's options of: (1) geometric expansion, CTV including the nodal gross tumor volume plus 5 mm margin: (2) lymph node stations, CTV including the affected lymph node stations. The 5 mm margins for planning target volume (PTV) were added to the nodal and primary tumors' CTVs. Treatment planning of 60 Gy in 30 fractions to the PTV D50% was performed using volumetric modulated arc therapy; Dn% was irradiated dose to n% of volume of the structure; VnGy was percentage of volume of the structure at least irradiated n Gy. We compared dose-volume parameters between the two options using Wilcoxon rank sum test. Primary tumors were located in the right and left lobes in 12 and five patients, and in the upper and lower lobes in 13 and four patients, respectively. Median PTV size/D95% of the options for geometric expansion and lymph node stations were 569 cc (range, 149-2005 cc)/58.2 Gy (range, 57.5-58.7 Gy) and 635 cc (range, 184-2109 cc)/58.1 Gy (range, 57.5-58.7 Gy), respectively. Median mean dose of the esophagus/heart in the two options were 12.2 Gy (range, 6.6-24.9 Gy)/3.3 Gy (range, 0.6-19.1 Gy) and 16.1 Gy (range, 13.6-30.5 Gy)/4.6 Gy (range, 0.7-18.9 Gy), respectively. Median V20 Gy/mean dose of the lungs in the options for geometric expansion and lymph node stations were 20.5% (range, 14.8-33.9%)/12.2 Gy (range, 8.7-18.4 Gy) and 24.0% (range, 15.1-36.7%)/13.5 Gy (range, 9.5-19.4 Gy), respectively. In the eight patients (47%) with lymph node metastases in stations 2 or 3, a significant dosimetric difference between the two options existed on V20 Gy of the lungs; median values of the difference were 2.8% and 0.5% with and without lymph node metastases in stations 2 or 3, respectively (p = 0.027). Of the ESTRO guideline for the nodal CTV, using the option for geometric expansion might be able to reduce V20 Gy of the lungs in patients with lymph node metastases in stations 2 or 3.

AI Serial Image Prediction of Progression-Free Survival (PFS) for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) Patients Treated with Chemoradiation (CRT) and Durvalumab Consolidation

Patient outcomes with definitive CRT for LA-NSCLC remain poor, with no imaging biomarkers to predict benefit. Hence, we developed a serial image AI model using paired planning CT (pCT) and first week cone-beam CT (CBCT) to predict PFS and measured AI model fairness defined as the bias in the classification with respect to gender as a protected attribute. Sixty-four consecutive patients with LA-NSCLC treated with concurrent CRT to 60 Gy in 30 fractions and durvalumab consolidation were analyzed. Three prediction models were created. A previously developed AI image foundation model [1] was pre-trained with unlabeled 6,402 3D CT scans sourced from institutional and the Cancer Imaging Archive and modified to predict PFS as a binarized outcome (high PFS > 6 months and low PFS < 6 months) using pCT scans. Serial image AI model was created by adding the first week CBCT scan. The third model measured tumor growth rate (TGR) as relative change in tumor and nodal volume from pCT to CBCT derived using a different published AI model [2]. Association with PFS using univariable and multivariable Cox regression after adjusting for age, gender, planning tumor volume, and smoking status were measured using TGR and the two AI model predictions using a cutoff of > 50% probability for low PFS. AI model fairness metrics area under receiver operating curve (AUROC), precision, sensitivity, and specificity were computed. TGR was not associated with PFS on univariate (Hazard ratio [HR] of 1.515, 95% confidence interval [CI] of 0.32 to 7.26, p = 0.60) or multivariate analysis (HR: 1.58, 95% CI: 0.32 to 7.80, p = 0.58) and resulted in a Harrell's C-index of 54.7%. The serial image AI model prediction was associated with PFS in both univariable (HR: 2.12, 95% CI: 1.02 to 4.40, p = 0.045) and multivariable analysis (HR 2.39, 95% CI of 1.09 to 5.25, p = 0.029), and a C-index of 62.5%. The pCT AI model was associated with PFS in univariate (HR 2.06, 95% CI of 1.06 to 4.01, p = 0.034) but not in multivariable analysis (HR 1.89, 95% CI of 0.93 to 3.87, p = 0.08), and a C-index of 59.9%. The serial image AI model reduced the parity in classification compared to pCT AI model indicating higher fairness (Table I). The multi-image AI model predicted PFS with slightly higher accuracy and resulted in higher fairness than the pCT AI model. These results underscore the potential for incorporating multi-imaging biomarkers to predict treatment response.

Longitudinal Monitoring of Quantitative Imaging Kinetics of Primary Tumor and Nodal Volumes Using the MR-Linac Device in Head and Neck Cancer Patients

We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients. Thirty patients with pathologically confirmed HNSCC and received curative-intent RT at the University of Texas MD Anderson Cancer Center, were included in this prospective study. Baseline and weekly MRIs (weeks 1-6) were obtained, and various ADC parameters (mean, 5th, 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, 90th and 95th percentile) were extracted from the target regions of interest (ROIs). Pre-RT and weekly ADC parameters were correlated with response during RT, loco-regional control, and the development of relapse using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman's Rho test. Recursive partitioning analysis (RPA) was performed to identify the optimal ΔADC threshold associated with different oncologic outcomes. There was an overall significant rise in all ADC parameters during different time points of RT compared to baseline values for both GTV-P & GTV-N. The increased ADC values for GTV-P were statistically significant only for primary tumors achieving CR during RT. RPA identified GTV-P ΔADC 5th percentile >13% at the 3rd week of RT as the most significant parameter associated with CR for GTV-P during RT (p <0.001). Baseline ADC parameters didn't significantly correlate with response to RT or other oncologic outcomes. There was a significant decrease in residual volume of both GTV-P & GTV-N throughout the course of RT. Additionally, a significant negative correlation between mean ΔADC and Δvolume for GTV-P at the 3rd and 4th week of RT was detected (r = -0.39, p = 0.044 & r = -0.45, p = 0.019, respectively). Assessment of ADC kinetics at regular intervals throughout RT is potentially able to predict the response to RT and oncologic outcome. Further studies with larger cohorts and multi-institutional data are needed for validation of our results.

Automated Contouring of Cervical Lymph Nodes and Clinical Target Volumes for Nasopharyngeal Carcinoma Based on Deep Learning and Experience Constraints

Application of artificial intelligence (AI) for automated contouring of tumor volumes and organs at risk (OARs) for radiotherapy of nasopharyngeal carcinoma (NPC) leads to improved contouring accuracy and efficiency. However, few studies have involved the automated contouring of gross tumor volume of cervical lymph nodes (GTVn) and clinical target volumes (CTVs). In this work, we proposed an AI automated contouring tool for GTVn and CTVs for radiotherapy of NPC on the plain scans of planning compute tomography (CT). In this retrospective study, plain scan datasets of planning CT covering the nasopharynx and neck from 139 patients with NPC between March 2022 and December 2022 were collected and divided into training, validation, and testing cohorts of 95, 24, and 20 patients, respectively. Ground truth contours of primary gross tumor volume (GTVp), GTVn (divided into GTVn_L in left neck and GTVn_R in right neck), CTVs (including high risk CTV1 contains GTVp and low risk CTV2 contains GTVp and cervical nodal levels) and OARs were delineated and were defined by consensus of two experts. We first proposed a three-dimensional (3D) U-net using GTVp and OARs as experience constrains to guide the automated delineation of GTVn and CTVs. The average Dice similarity coefficient (DSC) and average surface distance (ASD) were used to quantify the performance of the AI tool. Next, five prospective patients were enrolled for clinical evaluation of our AI tool. DSC between automated contours and radiation oncologist-revised contours and time consuming of the revision were record. Clinical characteristics of 139 retrospective and 5 prospective patients are list in Table 1. In the independent testing set of 20 patients, our AI tool showed high performance in GTVn and CTVs contouring when compared with the ground truth contours. The mean DSC were 0.73 ± 0.07, 0.74 ± 0.05, 0.93 ± 0.03, and 0.88 ± 0.03, and the mean ASD were 1.01 ± 0.43 mm, 1.14 ± 0.61 mm, 0.51 ± 0.13 mm, 1.17 ± 0.43 mm for GTVn_L, GTVn_R, CTV1 and CTV2, respectively. In the five prospective patients, mean DSC were 0.74 ± 0.07, 0.74 ± 0.10, 0.95 ± 0.01 and 0.89 ± 0.04, respectively. The median time consuming for GTVn and CTVs revision was 2minutes and 10 seconds (range, 1 minutes to 3 minutes). The proposed AI tool integrating clinical experience as constrains showed high accuracy for contouring GTVn and CTVs of NPC. With the assistance of AI contours, contouring efficiency could be probably increased, which is promising in online adaptive radiotherapy of NPC.

Feasibility of Omitting Contralateral Neck Irradiation in Patients with Node-Negative Sinonasal Squamous Cell Carcinoma Crossing the Midline

This study aims to analyze the nodal target volume in patients with node-negative SNSCC crossing the midline. One hundred and four patients with node-negative advanced sinonasal squamous cell carcinoma (SNSCC) crossing the midline were included. Survival rates were estimated and compared between treatment groups. Sixty-four patients received contralateral ENI (contralateral ENI group), while forty patients did not (non-contralateral ENI group). The median follow-up time was 89.99 and 95.01 months in the contralateral and non-contralateral ENI groups, respectively. At 5 years, the regional relapse-free survival and contralateral regional relapse-free survival were 57.68% vs. 55.83% (p = 0.372), and 57.68% vs. 61.62% (p = 0.541), in contralateral ENI group vs. non-contralateral ENI group, respectively. Five-year overall survival, local relapse-free survival, and distant metastasis-free survival were similar in the two groups (all p > 0.05). In patients with node-negative SNSCC crossing the midline, omission of contralateral ENI did not affect regional control and survival outcomes on the premise of receiving ipsilateral ENI covering at least levels Ib and II.

Dosimetric Benefits of Online Adaptive Radiotherapy in Nasopharyngeal Carcinoma

Online adaptive radiotherapy (ART) has the advantage of compensating for potential underdosing to targets and overdosing to organs-at-risk (OARs) caused by variations in patient anatomy and tumor geometry. Artificial intelligence (AI)-assisted rapid generation of new plans makes online ART possible. We aimed to evaluate the dosimetric benefits of online ART on tumor coverage and OARs sparing in nasopharyngeal carcinoma (NPC). Twenty patients diagnosed with NPC (19 with stage III and 1 with stage II according to the 8th edition of the AJCC/UICC staging system) who underwent definitive radiotherapy or concurrent chemoradiotherapy and received online ART on CT-Linac between April 2022 and December 2022 were included in this study, consisting of 14 males and 6 females with a median age of 48 years (range: 29-68 years). The prescription dose was 6996 cGy/33 fractions for primary gross tumor volume (GTVp), 6600-6996 cGy/33 fractions for gross tumor volume of nodes (GTVn), 6006 cGy/33 fractions for high-risk clinical tumor volume (CTV1), 5412 cGy/33 fractions for low-risk clinical tumor volume (CTV2). The majority of the patients (15/20) received online ART during the fourth to fifth week of their radiotherapy treatment The auto-segmented contours and auto-plan generated by AI were manually reviewed and edited by radiotherapists and physicists. The paired samples t-test was used to compare the dose and volumes metrics of targets and OARs between scheduled plan and online ART plan. The results of this study showed that compared to the scheduled plan, the online ART plan resulted in significant reductions in the volumes of all targets and 8/12 OARs (temporal lobes, optic nerves, lenses, eyes, parotids, submandibulars, mandibles, and thyroid) (P<0.05). The online ART plan also improved target coverage, with D98% for GTVp in the scheduled plan compared to the online ART plan being 7063.4 ± 76.1 cGy and 7096.1 ± 53.9 cGy (P = 0.1), CTV1 being 6266.7 ± 114.9 cGy and 6208.7 ± 54.7 cGy (P<0.05), and CTV2 being 4142.5 ± 1700.9 cGy and 5416.4 ± 23.8 cGy (P<0.01), respectively. The dose to all 12 OARs was reduced with the use of online ART, with 5/12 OARs showing statistical significance. The D0.03cm3 for the spinal cord in the scheduled plan and online ART plan were 3630.9 ± 197.6 and 3454.1 ± 132.0 cGy; for the temporal lobes were 7075.2 ± 303.0 and 6994.2 ± 345.1 cGy; and 4396.0 ± 2575.0 and for the pituitary were 4214.5 ± 2499.2 cGy. Meanwhile the Dmean for the eyes in the scheduled plan and online ART plan was 769.0 ± 232.0 and 714.8 ± 200.1 cGy; and for the mandibles were 3187.7 ± 211.5 and 3066.0 ± 152.1 cGy. Online ART was effective in protecting most of the OARs in NPC patients, while simultaneously indicating a trend towards enhancing target coverage. This study demonstrated the promising potential of online ART for patients with NPC. This approach will be tested in an upcoming phase III trial.

Spatiotemporal Optimization of Pelvic Radiation Therapy

Conformal and adaptive Radiation Therapy (RT) remains critical in the treatment of locally advanced pelvic cancers despite acute and late bowel complications. This work introduces spatiotemporal optimization of pelvic RT including mathematical modelling of intestinal radiobiology to evaluate a novel treatment planning approach for fractionated pelvic RT. A single-plan fractionated RT delivery has n-fractions at dose/fraction = d and has biologically effective dose BED = nd ( 1 + d / [α/β] ) - ln(2) ([T - Tk] / [αTp]), where Tk and Tp are the kickoff time and doubling time of repopulation, and T is the time to deliver all fractions (including off-days). We present a parameterization of the repopulation BED-term to estimate a range of daily recovered BED including uncertainties in α and Tp. Recovery of BED as currently formulated is independent of the delivered dose; however, the assumption of spatiotemporal optimization is that a regional reduction of dose during RT by mixing treatment plans is critical to allow for normal tissue healing. We evaluate an achievable spatiotemporal optimization treatment planning strategy for an advanced stage prostate and a cervical cancer patient using 25-fraction delivery over 5-weeks and 4-weekends (T = 33 days) and propose 3 treatment plans: (1) a conformal "clinical standard" plan, (2) a right-bowel sparing plan, and (3) a left-bowel sparing plan. The plans are optimized to ensure no increased dose in opposing bowel or normal organs at risk (OARs). For radiobiological parameters ranging from α = 0.2-0.35/Gy, α/β = 2-3 Gy, Tk = 5-10 days, and Tp = 3-7 days, parameterization shows daily BED recovery of 0.44±0.08 Gy (range = 0.28-0.69 Gy), or an average of 4Gy BED recovery for 5-days treatment surrounded by 2 weekends. Conservatively evaluating the 3.6Gy BED distribution in treatment planning may identify regions for complete recovery (after Tk days). In a prostate 3-plan set, the right- and left- bowel sparing plans deliver equivalent mean dose to targets and OARs to within 5cGy/fx. The clinical plan includes 298cc of bowel under 14Gy, but this same bowel will be spared throughout treatment. Delivery of the clinical plan in week 1 to achieve Tk days, followed by alternating the left and right plan each week has the potential to reduce BED to zero for an additional 116cc of bowel using the left-sparing plan in weeks 2 and 4, and 91cc using the right-bowel sparing plan in weeks 3 and 5. The cervical cancer plan-set was more challenging due to right-sided nodal volumes and higher clinical bowel dose; OAR mean dose variations were >8cGy/fx in a few organs, but the left- and right- sided sparing plans results in 394 cc and 139cc, respectively of unique spared bowel at the 3.6Gy/week threshold to potentially reach zero BED during treatment. A novel spatiotemporal optimization of pelvic RT has the potential to preserve bowel, allow for increased intra-treatment intestinal tissue regeneration, and reduce radiation-induced complications.

Evaluation of Metastatic Potential in Esophageal and Gastroesophageal Junction (GEJ) Cancer with Adherence to Elective Nodal Volume Guidelines: A Retrospective Analysis of Elective Nodal Irradiation

In 2015, expert guidelines on esophageal/GEJ cancer contouring for intensity-modulated radiation therapy (IMRT) were published in IJROBP, which delineate recommended elective nodal basins (celiac, para-aortic, gastrohepatic ligament, supraclavicular) to be irradiated depending on the primary tumor location. We hypothesize that incomplete coverage of these areas increases the risk of the development of distant failures. Patients treated for non-metastatic esophageal or GEJ cancer with chemoradiotherapy pre-operatively or definitively from 2012 to 2021 were retrospectively identified from a single institution database. Radiation plans of eligible patients were then analyzed by tumor location. Plans were deemed guideline-compliant if radiation dose coverage, between 41.4 to 45 Gy, encompassed nodal basins recommended by the 2015 guidelines. The primary endpoint of this study was the overall rate of distant disease. Other endpoints included locoregional failures, defined as failures within the radiation field but outside of the primary tumor, and local failures within the gross tumor volume. Summary and descriptive statistics were used to define collected variables. Differences were measured using chi-square and Fisher's exact test for categorical variables and two-sided t-tests for continuous measures. Assessment of distant, locoregional, and local failures were assessed using univariate logistic regression with statistical significance at p < 0.05. With a median follow-up of 25.0 months, 37 patients, with a median age of 66, were included in the study. Most patients were male (94.6%) with cT3 (54.1%), cN0 (43.2%), moderately differentiated (47.1%) adenocarcinoma (75.7%) located at the GEJ (56.8%). The median radiation dose used was 50.4 Gy, with the majority of patients receiving concurrent carboplatin and paclitaxel (83.8%). Four patients received induction chemotherapy and 20 (55.6%) underwent esophagectomy. When examining guideline compliance, 17 (46.0%) radiation plans demonstrated adequate ENI. The most common improperly covered nodal basin was para-aortic (65.0%), followed by gastrohepatic (30.0%). No patients with sufficient ENI coverage (0/17) developed distant failure compared to 45.0% (9/20) with insufficient coverage (p = 0.001). There were inappreciable differences in locoregional or local failure rates between those with and without complete ENI. Patients with complete ENI were more likely to be of larger craniocaudal length (p = 0.007) or have N2 disease (p = 0.003). When examining other tumor characteristics (histologic subtype, location, HER2 status, esophagectomy rate) of patients with and without complete ENI, no further differences were noted. These results suggest that proper coverage of nodal basins, when indicated by expert guidelines, could improve distant metastasis. ENI analysis of previous prospective CRT studies for esophageal cancer could validate these findings.

An Update of Stereotactic Body Radiotherapy (SBRT) for the Palliation of Unirradiated Mucosal Head and Neck Squamous Cell Carcinoma (SCC)

We report the treatment outcomes of palliative Stereotactic Body Radiation Therapy (SBRT) in patients with primary mucosal head and neck cancer (HNC) who were not eligible to receive conventional radiation therapy (RT). This is a retrospective study that reviewed the medical records of patients with primary SCC mucosal HNC who were treated with SBRT between 2011 and 2022. Patients with other histologies, skin cancer, parotid tumors, or recurrent previously irradiated tumors were excluded from the study. A total of 74 patients and 77 tumors were treated with SBRT in this cohort. The median age in the study was 81 (52-97) years and the median follow-up was 7.2 months. The most common site of HNC was the oral cavity (62%), followed by the oropharynx (18%), hypopharynx (8%), larynx (5%), nasal cavity/sinonasal cancer (3%), and unknown primary (1%). T3-4 lesions were found in most patients (76%). SBRT doses ranged from 35-50 Gy in 5 fractions, and the most common prescription dose was ≥45 Gy in 5 fractions (60%) for the GTV prescription. An elective nodal volume of 25 Gy in 5 fractions was infrequently (17%) used. Most patients (81%) who were treated twice a week completed in ≤14 days. The predominant symptoms at presentation were: pain (41%), mass effect (39%), dysphagia/odynophagia (14%), headache/nasal obstruction (1.4%), bleeding (1.4%), stridor (1.4%), asymptomatic (1.4%), and unknown (1.4%). 84% of patients had symptomatic response to treatment with 24% of them having complete symptom response. Cumulative incidence of local failure (LF) was 6.7% and at 6 months and 17.9% at 12 months, respectively. Cumulative incidence of distant metastasis was 7.3% and 10.5% at 6 and 12 months. Cancer was the most common cause of death in 29 patients (51%). The median overall survival (OS) was 8 months with 6 and 12-month OS rates of 67% and 36%, respectively. 39% of patients developed acute G3 toxicity, including 30% with G3 mucositis, 5% with G3 dysphagia, and 4% with G3 dermatitis. A crude rate of late G ≥3 toxicity was observed in 11% of patients including (5%, n = 4) with osteoradionecrosis, and a single case of dysphagia, soft tissue necrosis, supraglottic ulceration, and mucosal necrosis. This study highlights the feasibility of SBRT as a treatment option for primary mucosal head and neck cancer patients who are not eligible for conventional radiation therapy. The results indicate that SBRT was effective in achieving local control and symptom relief, but larger prospective studies are needed to confirm the findings. The Canadian Cancer Trials Group has endorsed HN-13, a randomized control trial comparing HN SBRT to palliative RT.

Outcomes of Sentinel Lymph Node Biopsy for Patients With Node-positive Breast Cancer Treated With Neoadjuvant Chemotherapy.

Clinical trials have shown that the sentinel lymph node biopsy (SLNB) is feasible for patients with cN1 breast carcinoma treated with neoadjuvant chemotherapy (NAC). This study aimed to evaluate the technical outcomes of SLNB by assessing the volume of residual nodal disease. All patients with cT1-3 cN1 breast cancer undergoing NAC from January 2018 to December 2021 were retrospectively identified from our institutional database. We assessed the outcomes of preoperative clinical examination, ultrasonography, and other imaging to predict the axillary nodal status after NAC for patients converted to cN0 and undergoing SLNB; both adequate mapping and false-negative rate (FNR) at intraoperative evaluation of SLN were assessed. Overall 160 patients were included in the study; 98 were converted to cN0 and underwent SLNB. No difference was found in the adequate mapping rate nor in the mean number of SLNs retrieved compared to the residual LN burden. The intraoperative SLN FNR was 38.2%, with smaller nodal volume being associated with lower FNR (p<0.01). The positive predictive values of physical examination and imaging-based nodal assessment post-NAC were 87.1% and 68.2%, respectively. In a significant percentage of patients with cN1 disease converted to cN0 after NAC, it was possible to recover three or more SLNs. The residual volume of LN disease did not impact the SLN mapping rate. However, we found a high FNR for intraoperative SLN evaluation, particularly for patients with small residual nodal disease. It seems that only a small proportion of patients eligible for SLNB after NAC can be spared ALND.

Abstract PO-044: Correlation between circulating tumor DNA and tumor volume in head and neck cancer

Abstract Purpose: NavDx is a DNA test that has been used widely in head and neck cancer to quantify fragments of circulating tumor tissue modified viral DNA (TTMV HPV DNA), an HPV-specific cancer biomarker that is shed into the blood. Circulating tumor DNA has shown promise in monitoring tumor progression and therapeutic efficacy and therefore has potential to assist in improved cancer diagnosis and treatment. Recent studies have demonstrated a correlation between circulating tumor DNA and tumor volume in metastatic pancreatic ductal adenocarcinoma and metastatic breast cancer. The purpose of the study is to determine whether there is a correlation between positive vs. negative circulating tumor DNA at baseline as well as the quantity of circulating fragments and tumor volume in head and neck cancer patients. Methods: In this retrospective cohort study, data was extracted from our NavDx database (Naveris Systems) for 39 patients with p16 positive head and neck cancer with subsites in the base of tongue and tonsil. Logistic regression analyses were performed to compare tumor volume and tumor site in all patients and then by the subsites of base of tongue and tonsil. To address multicollinearity, different models were created for primary tumor volume, nodal volume, and total tumor volumes. Contrast enhanced diagnostic or radiation treatment planning CT scans were imported into Varian Aria (Varian Medical Systems, Palo Alto, CA). The primary and nodal disease was delineated to determine the total and sub-volumes. The relationship was examined between the tumor volumes and positive vs. negative/indeterminate circulating tumor DNA. Linear regression analysis was also performed to assess the relationship between tumor volumes and circulating fragments of TTMV-HPV 16. Results: A total of 39 patients were included in the study, including 36 males and 3 females, ages ranging from 42 to 79, and patients staged from Stage I to Stage IVA. 13 patients underwent surgical intervention. Subsites included the tonsil for 21 patients and base of tongue for 19 patients that were included in the analysis. There was a positive correlation between nodal volume and circulating TTMV-HPV16 fragments (p= 0.024) in all patients. There was a difference in tumor volume with an odds ratio of 1.41 and nodal volume with an odds ratio of 1.04 compared with positive vs. negative circulating DNA in all patients (p = 0.374; p = 0.906). Conclusions: The data demonstrated a positive correlation between nodal volume and circulating TTMV-HPV 16 fragments (p = 0.024). There was a difference in tumor and nodal tumor volumes with positive vs. negative circulating tumor DNA in all patients, however this did not reach statistical significance. While there was an association with nodal volume, further investigation is needed to determine why patients with p16 positive head and neck cancer may have negative serum circulating tumor DNA. Additional studies with a larger sample size can also better elucidate the relationship between circulating tumor DNA and tumor burden in H&amp;N patients. Citation Format: Oghenefejiro Okifo, Vivian Wu, Samantha Tam, Sondos Al Khatib, Farzan Siddiqui. Correlation between circulating tumor DNA and tumor volume in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-044.

QRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis.

One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.

Feasibility and Clinical Acceptability of Automation-Assisted 3D Conformal Radiotherapy Planning for Patients With Cervical Cancer in a Resource-Constrained Setting.

The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system. We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety metrics, and clinical acceptability by two ORCI physician investigators. Dice similarity coefficient (DSC) agreement analysis was conducted between original and new contour sets. The average time to manually develop treatment plans was 7 days. Applying RPA, automated same-day contours and plans were developed for 29 of 30 patients (97%). Of the 29 evaluable contours, all were approved with <2 minutes of edit time. Agreement between clinical and RPA contours was highest for the rectum (median DSC, 0.72) and bladder (DSC, 0.90). Agreement was lower with the primary tumor clinical target volume (CTVp; DSC, 0.69) and elective nodal clinical target volume (CTVn; DSC, 0.63). All RPA plans were approved with <4 minutes of edit time. RPA target coverage was excellent, covering the CTVp with median V45 Gy 100% and CTVn with median V45 Gy 99.9%. Automation-assisted 3DCRT contouring yielded high levels of agreement for normal structures. The RPA met all planning safety metrics and sustained high levels of clinical acceptability with minimal edit times. This tool offers the potential to significantly decrease RT planning timelines while maintaining high-quality RT delivery in resource-constrained settings.

Comparison of the effectiveness of lauromacrogol injection for ablation and microwave ablation in the treatment of predominantly cystic thyroid nodules: a multicentre study

PurposeTo compare the therapeutic efficacy and safety of microwave ablation (MWA) and lauromacrogol injection for ablation (LIA) for benign predominantly cystic thyroid nodules.Materials and methodsIn this retrospective study, 85 patients with predominantly cystic thyroid nodules (PCTNs) who underwent microwave ablation (MWA) or lauromacrogol injection for ablation (LIA) between June 2019 and August 2022 at three hospitals were included in our research. Forty-six patients were treated with microwave ablation, and thirty-nine patients were treated with lauromacrogol injection for ablation. The baseline characteristics, nodal volume, volume reduction rate (VRR), and incidence of postoperative complications were compared between these two groups.ResultsAfter treatment, there were significant differences in the thyroid nodule volume and the volume reduction rate (VRR) at different follow-up times between the groups (p < 0.001). There were no significant differences in the nodal volume or the volume reduction rate (VRR) between the MWA group and the LIA group at 1, 3, 6, and 12 months (p > 0.05). Of note, no serious intraoperative or postoperative complications occurred in the corresponding group.ConclusionMWA and LIA are very effective and safe strategies for the treatment of predominantly cystic thyroid nodules. However, LIA is more advantageous in that it is less expensive and has a shorter length of hospital stay than MWA.

Nodal tumor volume as a prognostic factor for oral squamous cell carcinoma-a systematic review.

Oral squamous cell carcinoma (OSCC) is a complex disease with a high potential for lymph node metastasis and poor survival rates. Accurate nodal staging is crucial for prognostic assessment and treatment planning in OSCC. Recent research has suggested that nodal tumor volume (NTV) may be a more accurate indicator of nodal disease burden than traditional staging methods. However, the prognostic significance of NTV in OSCC remains unclear. This systematic review aims to evaluate the existing evidence on the relationship between NTV and prognosis in OSCC. A comprehensive search of electronic databases was conducted, and studies meeting inclusion criteria were critically appraised and synthesized. Our review identified 23 studies that investigated the prognostic significance of NTV in OSCC. The majority of studies reported that larger NTV was associated with poorer survival outcomes, although the strength of the association varied. The review also identified several areas for future research, including the standardization of NTV measurement and the integration of NTV into the broader landscape of OSCC management. In conclusion, our review suggests that NTV holds promise as a novel prognostic factor in OSCC, but more research is needed to fully elucidate its potential and inform clinical decision-making.

Patterns of failure in nasopharyngeal cancer patients of northeastern region of India.

94 Background: We aimed to analyze patterns of failure and relationship between disease volume and treatment outcomes in patients of Nasopharyngeal cancer receiving chemoradiation at tertiary cancer centre in northeast region of India. Methods: From February 2018 to February 2022, 99 histopathologically proven non metastatic NPC patients treated with IMRT and chemotherapy were analysed retrospectively. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. Locoregional failures were classified as in-field or out-of-field in relation to the CT data sets used for pretreatment planning. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan-Meir curves were used to compare outcome variables based on classified tumour volume as determined by ROC analysis. Results: During a median follow up of 25.4 months (17.3-39.2), 35 (35.4%) patients developed recurrence. Twenty-nine patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10 and 74.10 % respectively. There was statistically significant difference in locoregional failure-free survival according to T staging (p&lt;0.0001). Cox regression analysis revealed that gross tumor volume(GTVp) and gross nodal volume(GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p=0.03) and GTVn (p=0.00024) and were superior to T classification for predicting prognosis of NPC patients. Conclusions: Distant failure is most common pattern of failure. With advanced T-stage NPC, locoregional failure is more common. GTVp and GTVn are an independent prognostic factor in local control, distant metastasis, disease-free survival, and overall survival in NPC. This justifies their use as quantitative prognostic indicator for NPC.