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1. Investigation of autosegmentation techniques on T2‐weighted MRI for off‐line dose reconstruction in MR‐linac workflow for head and neck cancers

   https://doi.org/10.1002/mp.16582  

   McDonald, Brigid A. ; Cardenas, Carlos E. ; O'Connell, Nicolette ; Ahmed, Sara ; Naser, Mohamed A. ; Wahid, Kareem A. ; Xu, Jiaofeng ; Thill, Dan ; Zuhour, Raed J. ; Mesko, Shane ; et al ( July 2023 , Medical Physics)

   In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)‐linear accelerator (MR‐linac), the low‐resolution T2‐weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction.

   In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on‐board setup MRIs from the MR‐linac for off‐line reconstruction of delivered dose.

   Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by seven observers each. Ground truth contours were generated using a simultaneous truth and performance level estimation (STAPLE) algorithm. Twenty total autosegmentation methods were evaluated in ADMIRE: 1–9) atlas‐based autosegmentation using a population atlas library (PAL) of 5/10/15 patients with STAPLE, patch fusion (PF), random forest (RF) for label fusion; 10–19) autosegmentation using images from a patient's 1–4 prior fractions (individualized patient prior [IPP]) using STAPLE/PF/RF; 20) deep learning (DL) (3D ResUNet trained on 43 ground truth structure sets plus 45 contoured by one observer). Execution time was measured for each method. Autosegmented structures were compared to ground truth structures using the Dice similarity coefficient, mean surface distance (MSD), Hausdorff distance (HD), and Jaccard index (JI). For each metric and OAR, performance was compared to the inter‐observer variability using Dunn's test with control. Methods were compared pairwise using the Steel‐Dwass test for each metric pooled across all OARs. Further dosimetric analysis was performed on three high‐performing autosegmentation methods (DL, IPP with RF and 4 fractions [IPP_RF_4], IPP with 1 fraction [IPP_1]), and one low‐performing (PAL with STAPLE and 5 atlases [PAL_ST_5]). For five patients, delivered doses from clinical plans were recalculated on setup images with ground truth and autosegmented structure sets. Differences in maximum and mean dose to each structure between the ground truth and autosegmented structures were calculated and correlated with geometric metrics.

   DL and IPP methods performed best overall, all significantly outperforming inter‐observer variability and with no significant difference between methods in pairwise comparison. PAL methods performed worst overall; most were not significantly different from the inter‐observer variability or from each other. DL was the fastest method (33 s per case) and PAL methods the slowest (3.7–13.8 min per case). Execution time increased with a number of prior fractions/atlases for IPP and PAL. For DL, IPP_1, and IPP_RF_4, the majority (95%) of dose differences were within ± 250 cGy from ground truth, but outlier differences up to 785 cGy occurred. Dose differences were much higher for PAL_ST_5, with outlier differences up to 1920 cGy. Dose differences showed weak but significant correlations with all geometric metrics (R2 between 0.030 and 0.314).

   The autosegmentation methods offering the best combination of performance and execution time are DL and IPP_1. Dose reconstruction on on‐board T2‐weighted MRIs is feasible with autosegmented structures with minimal dosimetric variation from ground truth, but contours should be visually inspected prior to dose reconstruction in an end‐to‐end dose accumulation workflow.

    

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2. Preoperative Radiomics Approach to Evaluating Tumor‐Infiltrating CD8 + T Cells in Patients With Pancreatic Ductal Adenocarcinoma Using Noncontrast Magnetic Resonance Imaging

   https://doi.org/10.1002/jmri.27871  

   Bian, Yun ; Liu, Cong ; Li, Qi ; Meng, Yinghao ; Liu, Fang ; Zhang, Hao ; Fang, Xu ; Li, Jing ; Yu, Jieyu ; Feng, Xiaochen ; et al ( August 2021 , Journal of Magnetic Resonance Imaging)

   CD8⁺T cell in pancreatic ductal adenocarcinoma (PDAC) is closely related to the prognosis and treatment response of patients. Accurate preoperative CD8⁺T‐cell expression can better identify the population benefitting from immunotherapy.

   To develop and validate a machine learning classifier based on noncontrast magnetic resonance imaging (MRI) for the preoperative prediction of CD8⁺T‐cell expression in patients with PDAC.

   Retrospective cohort study.

   Overall, 114 patients with PDAC undergoing MR scan and surgical resection; 97 and 47 patients in the training and validation cohorts.

   Breath‐hold single‐shot fast‐spin echo T2‐weighted sequence and noncontrast T1‐weighted fat‐suppressed sequences.

   CD8⁺T‐cell expression was quantified using immunohistochemistry. For each patient, 2232 radiomics features were extracted from noncontrast T1‐ and T2‐weighted images and reduced using the Wilcoxon rank‐sum test and least absolute shrinkage and selection operator method. Linear discriminative analysis was used to construct radiomics and mixed models. Model performance was determined by its discriminative ability, calibration, and clinical utility.

   Kaplan–Meier estimates, Student's t‐test, the Kruskal–Wallis H test, and the chi‐square test, receiver operating characteristic curve, and decision curve analysis.

   A log‐rank test showed that the survival duration in the CD8‐high group (25.51 months) was significantly longer than that in the CD8‐low group (22.92 months). The mixed model included all MRI characteristics and 13 selected radiomics features, and the area under the curve (AUC) was 0.89 (95% confidence interval [CI], 0.77–0.92) and 0.69 (95% CI, 0.53–0.82) in the training and validation cohorts. The radiomics model included 13 radiomics features, which showed good discrimination in the training cohort (AUC, 0.85; 95% CI, 0.77–0.92) and the validation cohort (AUC, 0.76; 95% CI, 0.61–0.87).

   This study developed a noncontrast MRI‐based radiomics model that can preoperatively determine CD8⁺T‐cell expression in patients with PDAC and potentially immunotherapy planning.

   5

   Stage 2

    

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3. Optimization of active surveillance strategies for heterogeneous patients with prostate cancer

   https://doi.org/10.1111/poms.13800  

   Zhang, Zheng ; Denton, Brian T. ; Morgan, Todd M. ( July 2022 , Production and Operations Management)

   Prostate cancer (PCa) is common in American men with long latent periods, during which the disease is asymptomatic. Active surveillance is a monitoring strategy commonly used for patients diagnosed with low‐risk PCa who may harbor latent high‐risk PCa. The optimal monitoring strategy attempts to minimize the disutility of testing while ensuring that the patient is detected at the earliest time when the disease progresses. Unfortunately, guidelines for the active surveillance of PCa are often one‐size‐fits‐all strategies that ignore the heterogeneity among multiple patient types. In contrast, personalized strategies based on partially observable Markov decision process (POMDP) models are challenging to implement in practice given the large number of possible strategies that can be used. This article presents a two‐stage stochastic programming approach that selects a set of strategies for predefined cardinality based on patients' disease risks. The first‐stage decision variables include binary variables for the selection of periods at which to test patients in each strategy and the assignment of multiple patient types to strategies. The objective is to maximize a weighted reward function that considers the need for cancer detection, missed detection, and cost of monitoring patients. We discuss the structure and complexity of the model and reformulate a logic‐based Bender's decomposition formulation that can solve realistic instances to optimality. We present a case study for the active surveillance of PCa and show that our model results in strategies that vary in intensity according to patient disease risk. Finally, we show that our model can generate a small number of strategies that can significantly improve the existing “one‐size‐fits‐all” guideline strategies used in practice.

    

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4. Prostate Cancer Risk Stratification via Nondestructive 3D Pathology with Deep Learning–Assisted Gland Analysis

   https://doi.org/10.1158/0008-5472.CAN-21-2843  

   Xie, Weisi ; Reder, Nicholas P. ; Koyuncu, Can ; Leo, Patrick ; Hawley, Sarah ; Huang, Hongyi ; Mao, Chenyi ; Postupna, Nadia ; Kang, Soyoung ; Serafin, Robert ; et al ( December 2021 , Cancer Research)

   An end-to-end pipeline for deep learning–assisted computational 3D histology analysis of whole prostate biopsies shows that nondestructive 3D pathology has the potential to enable superior prognostic stratification of patients with prostate cancer.

    

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5. Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points

   https://doi.org/10.1001/jamanetworkopen.2023.15250  

   Lin, Yannan ; Liang, Li-Jung ; Ding, Ruiwen ; Prosper, Ashley Elizabeth ; Aberle, Denise R. ; Hsu, William ( May 2023 , JAMA Network Open)

   Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence.

   To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points.

   This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021.

   Low-dose CT screening for lung cancer.

   The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography–CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time.

   Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69).

   In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

    

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