Regression Analysis of Rectal Cancer and Possible Application of Artificial Intelligence (AI) Utilization in Radiotherapy

Artificial Intelligence (AI) has been widely employed in the medical field in recent years in such areas as image segmentation, medical image registration, and computer-aided detection. This study explores one application of using AI in adaptive radiation therapy treatment planning by predicting the tumor volume reduction rate (TVRR). Cone beam computed tomography (CBCT) scans of twenty rectal cancer patients were collected to observe the change in tumor volume over the course of a standard five-week radiotherapy treatment. In addition to treatment volume, patient data including patient age, gender, weight, number of treatment fractions, and dose per fraction were also collected. Application of a stepwise regression model showed that age, dose per fraction and weight were the best predictors for tumor volume reduction rate.

Treatment of Plexiform Neurofibromas with MEK Inhibitors: First Results with a New Therapeutic Option

Neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PN) are peripheral nerve sheath tumors that can significantly affect the quality of life. Until recently, surgery was the only treatment for these tumors. However, in most cases, surgery cannot achieve complete tumor removal and carries a high risk of postoperative deficits. Therefore, the recent approval of the MEK inhibitor selumetinib for the treatment of NF1-associated PN provides a long-awaited novel therapeutic option. Here, we report our experience with MEK inhibitor treatment in 12 pediatric NF1 patients with inoperable symptomatic PN. Eight patients received trametinib (median therapy duration 12.13 months and range 4–29 months), and four patients received selumetinib (median therapy duration 6.25 months and range 4–11 months). Volumetric magnetic resonance imaging (MRI) after 6 months of treatment was available for seven trametinib patients (median tumor volume reduction of 26.5% and range 11.3–55.7%) and two selumetinib patients (21.3% tumor volume reduction in one patient and +3% tumor volume change in the other one). All patients reported clinical benefits such as improved range of motion or reduced disfigurement. Therapy-related adverse events occurred in 58.3% of patients and mainly consisted of skin toxicity, paronychia, and gastrointestinal symptoms. Two patients discontinued trametinib treatment after 14 and 29 months when severe skin toxicity occurred and no further reduction of tumor size was observed. In one patient, discontinuation of therapy resulted in a 27.2% tumor volume increase as demonstrated on volumetric MRI 6 months later. Our data show that MEK inhibition is a novel therapeutic approach for inoperable PN with promising results and a manageable safety profile.

Tumor Volume Reduction Rate to Induction Chemotherapy Is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Retrospective Cohort Study

BackgroundAim of this study was to evaluate the prognostic of tumor volume reduction rate (TVRR) status post induction chemotherapy (IC) in LA-HNSCC.MethodsPatients with newly diagnosed LA-HNSCC from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received IC as TPF (taxotere, platinum, fluorouracil) followed by daily definitive intensity-modulated radiotherapy (IMRT) for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate of the primary tumor (TVRR-T) and lymph node (TVRR-N) was measured and calculated by contrast-enhanced CT images at diagnosis, and one month after final IC cycle, and analyzed though a univariate and multivariate Cox regression model.ResultsNinety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%) and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In univariate Cox regression analysis, the TVRR-T as the only variable showed a significant difference for disease-free survival (DFS) (hazard ratio [HR] 0.77, 95% confidence interval (CI) 0.63 to 0.96; P = 0.02), aside from cancer site, RECIST, age and IC dose. In multivariate Cox regression analysis, The TVRR-T was also an independently significant prognostic factor for DFS (HR 0.77, 95% CI 0.62 to 0.97; P = 0.02). At a cutoff value using TVRR-T of 50% in Kaplan-Meier survival analysis, the DFS was significant higher with TVRR-T ≥ 50% group (log-rank test, p = 0.024), and also a trend of improved OS. (log-rank test, p = 0.069).ConclusionsTVRR-T was related to improved DFS and trend of improved OS. Other factors including patient’s age at diagnosis, the primary cancer site, and RECIST, were not significantly related to DFS.

391 Biomarker correlates of response in patients with advanced myxoid/round cell liposarcoma (MRCLS) treated with NY-ESO-1 TCR T cells (Letetresgene autoleucel)

BackgroundThis is an open label pilot study (NCT02992743) on letetresgene autoleucel (lete-cel; GSK3377794), an NY-ESO-1-specific autologous CD4+ and CD8+ T cells expressing a high affinity T-cell receptor which recognizes the NY-ESO-1 antigen epitope in complex with specific HLA- alleles A*02, which exhibited anti-tumor activity and manageable safety profiles in patients with advanced MRCLS based on interim analysis (IA) data.1 Lymphodepletion has been shown to enhance the expansion, persistence, and homing of therapeutically infused T-cells, thereby potentiating therapeutic efficacy against malignant diseases.2 Initial T-cell kinetics data from this study demonstrated that lymphodepletion regimen (LDR)-B robustly depleted lymphocytes at infusion and was trended with higher peak cell expansion (Cmax) vs. LDR-A. The peak expansion was significantly associated with weight-normalized transduced cell dose and trended with response.1 Here, we will be discussing additional cell kinetics data and other exploratory biomarker correlates of response.MethodsPatients with advanced MRCLS were enrolled to 2 cohorts and received either planned A (N=10) or B (N=10) LDRs prior to lete-cel infusion (table 1). Response was assessed per RECIST v1.1. Transduced cell kinetics were measured by quantitative PCR of transgene vector copies in DNA from peripheral blood mononuclear cells (PBMCs). Serum cytokines (Meso Scale Discovery immunoassay) as pharmacodynamic (PD) markers of response and their association with T cell kinetics will be discussed. Phenotypic characterization of the cell product (pre- and post- infusion) via Flow cytometry using Cytek Aurora (23 color panel), to help understand correlation of response with engineered cell product attributes, will be presented. Potential biomarker correlates of clinical response were tested using generalized linear models.ResultsFive out of 6 responders with available lab data exhibited robust lymphocyte depletion at infusion (0–25 cell/µL) and high Cmax (>50,000 vector copies/µg gDNA) with LDR. Only 6/14 non-responders exhibited low lymphocytes counts at infusion and high Cmax. LDR-B also induced strong depletion of monocytes at infusion (p=0.03) vs. LDR-A, but depletion of monocytes did not show association with response. Higher Cmax was correlated with exposure (AUC0–28d) (Adj. R2=0.606). AUC0–28d was a better predictor of response in patients receiving LDR-B (p=0.0182), with AUC0–28d trending towards predicting response in the LDR-A cohort. AUC0–28d was associated with tumor volume reduction (p=0.0569).Abstract 391 Table 1ConclusionsExposure–response analysis of this study reveals that efficacy appears to be driven by weight-normalized transduced cell dose and LDR via AUC0–28d. Higher AUC0–28d was correlated with Cmax and maximum tumor volume reduction.AcknowledgementsThis study (208469; NCT02992743) was funded by GlaxoSmithKline.Trial RegistrationNCT02992743ReferencesD’Angelo SP, et al. J Clin Oncol 2021;39:15_suppl:11521.Bechman, Maher. Expert Opin Biol Ther 2021;21(5):627–637.Ethics ApprovalThis study was approved by institutional review boards (IRB) at the six participating sites.

Assessment of radiation sensitivity of unresectable intrahepatic cholangiocarcinoma in a series of patients submitted to radioembolization with yttrium-90 resin microspheres

Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic 90Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α3D parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81–119) and its correlation with the residual tumor mass was statistically significant. The median of α and α3D parameters was 0.005 Gy−1 (95% CI 0.004–0.008) and 0.007 Gy−1 (95% CI 0.005–0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.

Evaluation of two different transarterial chemoembolization protocols using Lipiodol and degradable starch microspheres in therapy of hepatocellular carcinoma: a prospective trial

Background This prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response. Methods Sixty-one patients (44 men; 17 women; range 44–85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann–Whitney-U, Kruskal–Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan–Meier estimator. Results A mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5–41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6–38.4), for cTACE with Lipiodol-only (p = 0.844), respectively. Conclusions The additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed.

Efficacy and safety of prophylactic superselective embolization for angiomyolipoma at the renal hilum

Objective This study investigated the efficacy and safety of superselective transcatheter arterial embolization for angiomyolipoma at the renal hilum. Methods Between August 2012 and January 2015, 13 patients with 16 angiomyolipomas at the renal hilum underwent initial, prophylactic, superselective transcatheter arterial embolization. The patients were followed by computed tomography or magnetic resonance imaging, and volume-reduction ratios after embolization were measured. Results The mean or median post-embolization volume reduction ratios were 23% (follow-up duration, 1–2 months), 55% (3–6 months), 55% (7–12 months), 66% (1–2 years), 67% (2–3 years), and 54% (>3 years). After initial embolization, none of the 16 tumors bled or required surgery; two (13%) tumors recurred; and three (19%) tumors received repeat embolization. Estimated glomerular filtration rates were not decreased at medians of 7 days (near the time of discharge) and 39 days (first clinical follow-up) post-procedure, compared with baseline. Except for post-embolization syndrome, no procedure-related complications occurred. Conclusions Superselective embolization for renal hilar angiomyolipoma is safe and kidney-preserving, with good tumor volume reduction and bleeding prevention.

Characterization of circulating tumor cells in early breast cancer patients receiving neoadjuvant chemotherapy

Background and Aims: The aim of this study was to characterize circulating tumor cells (CTCs) during neoadjuvant chemotherapy (NACT) in early and locally advanced breast cancer (LABC) patients. Using ultrasound, tumor volume measurement was compared with the presence and the molecular nature of CTCs over multiple time intervals corresponding to treatment periods. Methods: A total of 20 patients diagnosed with breast cancer (BC) of different histotypes were monitored during the NACT period and in the follow-up period (~5 years). Peripheral blood for CTCs ( n = 115) was taken prior to NACT, after two to three chemotherapy cycles, after the completion of NACT (before surgery) and at some time points during adjuvant therapy. CTCs were enriched using a size-based filtration method (MetaCell®) capturing viable cells, which enabled vital fluorescence microscopy. A set of tumor-associated (TA) genes and chemoresistance-associated (CA) genes was analyzed by qPCR in the enriched CTC fractions. Results: The analysis of tumor volume reduction after administration of anthracyclines (AC) and taxanes (TAX) during NACT showed that AC therapy was responsive in 60% (12/20) of tumors, whereas TAX therapy was responsive in 30% (6/20; n.s.). After NACT, CTCs were still present in 70.5% (12/17) of patients (responders versus non-responders, 61.5% versus 100%; not significant). In triple-negative BC (TNBC) patients ( n = 8), tumor volume reduction was observed in 75% cases. CTCs were significantly reduced in 42.9% of all HER2-negative BC patients. In HER2+ tumors, CTC reduction was reported in 16.6% only. Relapses were also more prevalent in the HER2-positive patient group (28.5 versus 66.6%). During NACT, the presence of CTCs (three tests for each patient) identified patients with relapses and indicated significantly shorter progression-free survival (PFS) rates ( p = 0.03). Differentiation between progressive disease and non-progressive disease was obtained when the occurrence of excessive expression for CA genes in CTCs was compared ( p = 0.024). Absence of tumor volume reduction was also significantly indicative for progressive disease ( p = 0.0224). Disseminated CTCs in HER2-negative tumors expressed HER2 in 29% of samples collected during the overall follow-up period (16/55), and in 32% of samples during the follow-up of NACT (10/31). The change accounted for 78.5% of HER2-negative patients (11/14) in total, and 63.6% of the conversion cases occurred during NACT (7/11). For the remaining four patients (36.3%), conversion to HER2+ CTCs occurred later during adjuvant therapy. We believe there is the possibility of preventing further progression by identifying less responsive tumors during NACT using CTC monitoring, which could also be used effectively during adjuvant therapy.

Efficacy of prophylactic selective arterial embolization for renal angiomyolipomas: identifying predictors of 50% volume reduction

Background Transcatheter arterial embolization (TAE) has been widely performed for renal angiomyolipomas (AMLs) as prophylaxis or emergency treatment. On the other hand, mammalian target of rapamycin (mTOR) inhibitors have recently been used for tuberous sclerosis (TSC)-related AMLs, and no comparison between the effectiveness of mTOR inhibitors versus prophylactic selective TAE has yet been performed. Therefore, the purpose of this study was to evaluate the efficacy of TAE for AML tumor volume reduction and predictors of tumor volume decrease over 50%, with reference to the EXIST-2 trial. Methods A total of 44 patients who underwent 48 prophylactic embolization procedures for 50 AMLs in a single institution between 2004 and 2018 were included. Indications for TAE of AMLs were tumor size ≥4 cm or aneurysm ≥5 mm in diameter on contrast-enhanced computed tomography (CECT). Microspheres, ethanol, and micro-coils were used as embolic agents. The percentage volume reduction from before TAE to the minimum volume during follow-up after TAE was calculated, and predictors for 50% volume reduction were identified by univariate and multivariate binary logistic regression analyses. Results The technical success rate was 100% (50 of 50). No severe acute complications related to the procedure were encountered. Tumor volume reduction of ≥50% was observed in 35/50 AMLs. There was a significant difference in the rate of tumor volume reduction of 50% between the presence and absence of an aneurysm ≥5 mm and between tumor diameter ≥ 70 mm and < 70 mm on univariate analysis. On multivariate analysis, tumor diameter < 70 mm was the only independent predictor of significant tumor volume reduction after TAE. Conclusion Prophylactic selective TAE for AMLs has good tumor-reduction effects, especially for AMLs with tumor diameter < 70 mm.