A Deep Dive into Understanding Tumor Foci Classification using Multiparametric MRI Based on Convolutional Neural Network

Deep learning models have had a great success in disease classifications using large data pools of skin cancer images or lung X-rays. However, data scarcity has been the roadblock of applying deep learning models directly on prostate multiparametric MRI (mpMRI). Although model interpretation has been heavily studied for natural images for the past few years, there has been a lack of interpretation of deep learning models trained on medical images. This work designs a customized workflow for the small and imbalanced data set of prostate mpMRI where features were extracted from a deep learning model and then analyzed by a traditional machine learning classifier. In addition, this work contributes to revealing how deep learning models interpret mpMRI for prostate cancer patients stratification

FMEA of MR-Only Treatment Planning in the Pelvis

Purpose: To evaluate the implementation of a magnetic resonance (MR)-only workflow (ie, implementing MR simulation as the primary planning modality) using failure mode and effects analysis (FMEA) in comparison with a conventional multimodality (MR simulation in conjunction with computed tomography simulation) workflow for pelvis external beam planning. Methods and Materials: To perform the FMEA, a multidisciplinary 9-member team was assembled and developed process maps, identified potential failure modes (FMs), and assigned numerical values to the severity (S), frequency of occurrence (O), and detectability (D) of those FMs. Risk priority numbers (RPNs) were calculated via the product of S, O, and D as a metric for evaluating relative patient risk. An alternative 3-digit composite number (SOD) was computed to emphasize high-severity FMs. Fault tree analysis identified the causality chain leading to the highest-severity FM. Results: Seven processes were identified, 3 of which were shared between workflows. Image fusion and target delineation subprocesses using the conventional workflow added 9 and 10 FMs, respectively, with 6 RPNs \u3e100. By contrast, synthetic computed tomography generation introduced 3 major subprocesses and propagated 46 unique FMs, 15 with RPNs \u3e100. For the conventional workflow, the largest RPN scores were introduced by image fusion (RPN range, 120-192). For the MR-only workflow, the highest RPN scores were from inaccuracies in target delineation resulting from misinterpretation of MR images (RPN = 240) and insufficient management of patient- and system-level distortions (RPN = 210 and 168, respectively). Underestimation (RPN = 140) or overestimation (RPN = 192) of bone volume produced higher RPN scores. The highest SODs for both workflows were related to changes in target location because of internal anatomy changes (conventional = 961, MR-only = 822). Conclusions: FMEA identified areas for mitigating risk in MR-only pelvis RTP, and SODs identified high-severity process modes. Efforts to develop a quality management program to mitigate high FMs are underway

(P44) Is Prophylactic Cranial Irradiation Necessary in Stage I-IIA Small Cell Lung Cancer Patients? A Single Institution Experience

Background: The advent of screening chest computed tomography (CT) for high-risk patients has increased the patient population presenting with early-stage small cell lung cancer (SCLC). While surgical resection continues to be standard of care, stereotactic body radiation therapy (SBRT) is an option for non-surgical candidates. Although the effectiveness of PCI in patients with limited stage SCLC has been well established, decreasing the brain metastasis incidence from approximately 70% to 30%, the role of PCI in early-stage SCLC (T1-T2) has not been fully elucidated. This study reports our experience omitting PCI in early-stage SCLC. Objectives: This study reports our experience omitting PCI in early stage SCLC. Methods: Fourteen patients with early-stage SCLC, nine patients with clinical stage I (T1) and five patients with stage IA (T2) SCLC, ranging in age from 54-81 years old, treated with surgical resection or SBRT from July 2015 to May 2021 at our institution, were retrospectively reviewed. Positron emission tomography (PET) was used in the staging of 93% of patients. All patients had initial negative brain MRI and opted not to receive PCI. 71% of the patients had brain scan surveillance for follow-up. Risk factors including age, gender, and tumor size, were analyzed for overall survival (OS), loco-regional recurrence (LRR), and distant metastasis (DM) using the Log-rank test. Results: With a median follow-up of 13 months (range 2-63), none of our patients developed metastases to the brain. Adjuvant chemotherapy, with a mean of 4 cycles (2-6) was administered to 13 out of 14 patients (92%). The 2-year OS, LRR and DM estimates were 47% [95% CI (0.14, 0.75)], 57% [95% CI (0.19, 0.82)], and 51% [95% CI (0.17, 0.77)], respectively. The OS and the frequency of LRR were not found to be correlated with age, gender, or tumor size. DM was significantly higher in males vs females (P=0.016). Conclusions: Our experience in patients with Stage I-IIA SCLC treated with surgery or SBRT did not demonstrate any development of brain metastases. As PCI carries long term risks of neurotoxicity, close surveillance with regular brain imaging may be a reasonable alternative. Adjuvant systemic therapy remains an important component of treatment

Gold Nanoparticle (AuNP) as a Therapeutic Enhancer for Radio – And Immunotherapy Therapy Combination in Triple Negative Breast Cancer

Purpose/Objective(s): Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) form, with a high metastases rate and a very low survival. The aggressiveness of TNBC coupled with a significant toxicity and suboptimal chemotherapy outcomes underscores the urgency for new TNBC treatments. In recent years, immunotherapy has emerged as a promising option. In particular, immune checkpoint blockers (ICB) targeting PD-L1/PD1 inhibitory T cell check point pathway showed clinical responses and have been explored for TNBC. Unfortunately, the response rates to standalone ICB therapy are low (15-20%), indicating the presence of inhibitory immune mechanisms. Radiation therapy (RT) has been widely used in BC therapies. In addition to antitumor (antiproliferative) effects, RT has been evidenced to stimulate immune tumor rejection through immunomodulation of the tumor microenvironment (TME) that has been shown to enhance the response to immunotherapy in mouse BC models. Antitumor RT effects, including TME immunomodulation, can be improved by using radiosensitizers, such as gold nanoparticles (AuNPs). We hypothesize that AuNP potentiates RT-induced immunomodulatory effects, leading to a more efficient response to ICB in TNBC. To test this hypothesis, we used AuNP as an enhancer of RT-induced immunological TME changes, to improve ICB therapy response in murine orthotopic syngeneic 4T1Luc TNBC model. Materials/Methods: Female Balb/c mice bearing 4T1Luc tumors received intratumoral injections of 14 nm AuNPs. After 24h mice were irradiated with fractionated regimen of 3 × 6 Gy dose using 225 kV photons. After the 3rd RT dose, mice received 3 doses of anti-PD-L1 antibody that were 4 days apart. Therapeutic efficiency was determined by assessing the tumor growth and animal survival. Tumor tissue immunohistochemistry determined the expression of TME immunological markers and immune cell tumor infiltration. Results: AuNPs improved response to anti PD-L1 treatment in mice receiving RT, shown by significant delay in tumor growth and increase in survival compared to the animals receiving RT+ AuNP (p\u3c0.01) and to the animals receiving RT+ anti PD-L1 or RT alone (p\u3c0.05). These results were accompanied with changes in the expression of TME immunological markers and T cell and macrophage infiltration. Conclusion: In TNBC patients, induction of antitumor immune response may play a critical role in improving clinical outcomes. Here we show that AuNP enhanced the effect of a fractionated RT regimen that has significantly improved the response to anti PD-L1 treatment in 4T1Luc TNBC mouse model. This effect was measured by a delay in tumor growth and an increase in animal survival. These findings support the role of immunological mechanisms in TNBC and provide a platform for designing multimodal TNBC RT formulations with novel radiosensitizers or immunotherapy

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcome

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

Evaluation of Practice Patterns and Outcomes after Implementing SMART for Pancreatic Cancer

Purpose/Objective(s): Stereotactic MRI-guided adaptive radiation therapy (SMART) enables safe dose escalation for locally advanced, borderline resectable, and medically inoperable pancreatic cancer and has shown favorable toxicity and survival outcomes. In late 2018, our institution commissioned SMART for these patients, making it available to all patient referrals. We wanted to review changes in our patient population and differences in clinical outcomes for patients before and after the implementation of SMART. Materials/Methods: In this IRB approved analysis, we retrospectively reviewed 167 consecutive patients from 2015-2021 with locally advanced, borderline resectable, or medically unresectable pancreatic cancer who were treated with radiation therapy. Chemoradiation (chemoRT) was defined as any 28-30 fraction radiation regimen that included concurrent chemotherapy. SMART was defined as 50 Gy over 5 consecutive daily fractions without concurrent chemotherapy. Baseline patient characteristics were compared between groups. Overall survival (OS) was evaluated by Kaplan-Meier (KM) and log-rank test. Univariate (UVA) and multivariate analysis (MVA) were also performed on multiple treatment variables. Results: Of the patients included, 58 received chemoRT (2015-2018) and 109 received SMART (2018-2021). Median follow up from time of diagnosis for the chemoRT and SMART cohorts were 53.7 months and 29.2 months respectively. Cohorts did not have significant differences in age, gender, race, T or N staging, rates of surgery or surgical margin status. Patients receiving SMART had overall worse performance (p = 0.011) including a lower percentage of PS 0 patients (22.9% vs 44.8%) and a higher percentage of PS 2+ patients (34% vs 15.5%). Similarly, the SMART patients did numerically more often have locally advanced (50% vs 43%) and medically inoperable (26% vs 21%) disease (p = 0.294). The SMART cohort did have longer neoadjuvant chemotherapy with mean of 3.5 months vs 2.3 months in the chemoRT cohort (p = 0.002). There was no OS difference between each group when measured from diagnosis (p=0.79) or from first day of radiation (p=0.2). Median survival in the chemoRT and SMART groups was 18.7 vs 17.4 months from diagnosis. When including only PS 0-1 patients, the median survival in the chemoRT and SMART groups was 18.8 vs 22.3 months (p=0.37). There was also no difference in locoregional control, distant control, or progression free survival using KM. On MVA positive prognostic factors for OS from diagnosis included ECOG \u3c2 (HR 0.54, p=0.015), increasing months of neoadjuvant chemo (HR 0.88, p=0.004) and pancreatectomy (HR 0.14, p \u3c0.001). Conclusion: Despite the fact that the patient cohort receiving radiation therapy per the SMART approach had poorer performance status compared with chemoRT, OS was not significantly different. The multidisciplinary team was highly supportive of SMART with increased patients being treated

Development and evaluation of a clinical model for lung cancer patients using stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub-KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model\u27s ability to handle suboptimal beam placements. Dose differences to organs-at-risk (OAR) were evaluated between the plans gener-ated by each KBM. Knowledge-based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by 1.0 ± 1.6 Gy compared to clinical plans, p = 0.007. Sub-KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub-KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by 0.4Gy ± 0.8Gy, p = 0.025. For all lesions, compared to the full KBM, the posterior sub-KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by 0.2 ± 0.4Gy, p = 0.01. Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (1.2 ± 2.2Gy, p = 0.01) and GI (0.2 ± 0.4, p = 0.01) for the nine-field plans relative to KBPs planned with custom beam angles. A knowledge-based model for lung SBRT consisting of multiple treatment modalities and lesion loca-tions produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations