Pre-treatment PET-CT Research Articles

Training and external validation of pre-treatment FDG PET-CT-based models for outcome prediction in anal squamous cell carcinoma

ObjectivesThe incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models.MethodsConsecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres’ patient cohort.ResultsA total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4).ConclusionsA combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients.Clinical relevance statementA Cox regression model using patients’ age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing.Key Points• A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort.• The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data.• The predictive ability of positron emission tomography-computed tomography–derived radiomic features diminished when the influence of metabolic tumour volume was accounted for.

A Phase II Study of Loncastuximab Tesirine As Consolidation Strategy in Patients with LBCL in PR at Day 30 after CAR T-Cell Therapy

Background and Significance. Approximately 30% of patients with large B-cell lymphoma (LBCL) treated with autologous anti-CD19 CAR T-cell therapy (CART) achieve a partial response (PR) on day 30 (D30) assessment. Of those, up to 30% may spontaneously convert to a complete response (CR) during subsequent re-staging. While up to 70% of patients with D30 PR eventually progress, reliable biomarkers that help identify patients at risk are not yet available, and the current standard approach is close monitoring. CD19 expression is retained in most tumors of patients who relapse or progress after CART. Potential reasons for resistance in these tumors include T-cell dysfunction and tumor intrinsic mechanisms that resist T-cell mediated killing. Therefore, targeting such tumors with agents that have an alternative mechanism of action is likely to improve outcomes. To this regard, loncastuximab tesirine (Lonca) is an anti-CD19 antibody conjugated to a cytotoxic pyrrolobenzodiazepine dimer approved by the FDA for LBCL patients who relapse after at least 2 lines of systemic therapy. In the phase 2 LOTIS-2 study, Lonca was associated with an overall response rate of 48% and a CR rate of 24%, and included patients previously treated with CART. Grade 3-4 adverse events were observed in less than one third of patients, and were mainly represented by myelosuppression, skin toxicity and isolated GGT elevation. Study Design and Methods. This is a phase 2 single center study to investigate the safety and efficacy of Lonca as a consolidation strategy for LBCL patients with D30 PR after standard of care CART (NCT05464719). Patients with LBCL, including diffuse large B-cell lymphoma, high grade B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed follicular lymphoma, treated with standard of care CART (in second line and beyond) and with PET-CT evidence of D30 PR are eligible for this study. Patients with absolute neutrophil count < 1000/uL and/or platelet count < 50,000/uL, and those with previous or active central nervous system involvement are excluded. Tissue biopsy for confirmation of PR will be performed; CD19 expression is not required for eligibility. Lonca is administered intravenously, on day 1 of a 21-day cycle, at a dose of 150 mcg/kg for the first 2 cycles, and 75 mcg/kg subsequently, for a total of 6 cycles. Response is assessed by PET-CT, according to 2014 Lugano criteria, after 3 cycles and at the end of treatment. The primary objective is efficacy, measured as conversion from D30 PR to CR. Using a one arm binomial exact test, hypothesizing an increase in conversion rate to CR from 30% to 60%, a sample size of 30 patients has a 90% power to observe a significant difference, with an alpha error of 0.05; a futility analysis, based on efficacy and toxicity, will be performed after the first 10 patients are treated. Secondary objectives are safety and other measurements of efficacy, including duration of CR. Exploratory objectives include identification of biomarkers of response and resistance. Peripheral blood samples will be collected pre-treatment, after 3 cycles, post-treatment and at time of progression, as well as collection of a pre-treatment tissue biopsy and at time of progression. Blood and tissue samples will be analyzed by multi-parameter flow cytometry and hiplex imaging assays (Phenocycler-Fusion/CODEX) to identify immune signatures of response and resistance to Lonca, and to assess CAR T-cell persistence; blood samples will be analyzed by CAPP-Seq to measure minimal residual disease. Finally, total metabolic tumor volume will be assessed on pre-treatment PET-CT scans, and association with response to consolidation therapy will be analyzed.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT). We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4months following completion of IMPT were analyzed. Sixty patients were included for analysis with a median follow-up of 17 months. The median GTV to CTV expansion was 5 mm (IQR: 2 mm). Thirty-three percent of patients (20 of 60) did not have a GTV to CTV expansion. There was one local failure within the expansion group (3%). Excellent local control was achieved using IMPT for p16+ OPC independent of GTV expansion. IMPT with minimal target expansions represent a potential harm-minimization technique for p16-positive oropharynx cancer.

Survival effect of pre-RT PET-CT on cervical cancer: Image-guided intensity-modulated radiation therapy era.

No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). This is the first head-to-head propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT.

The Association of Preoperative PET-CT and Survival in Patients with Resectable Cervical Cancer.

No randomized study with a long-term follow-up has investigated the effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on the survival of patients with stage IB-IIA cervical cancer receiving curative surgery. Therefore, in this propensity score-matched, population-based cohort study, we investigated the effect of preoperative 18FDG-PET-CT on the survival outcomes of patients with potentially resectable cervical cancer. We included 2550 patients with stage IB-IIA cervical cancer receiving curative surgery with complete data on clinical stages. The patients were categorized into two 1:4 propensity, score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. We included 2030 and 520 patients with cervical cancer in the non-pretreatment and pretreatment PET-CT groups, respectively. Multivariable analyses revealed that the most prominent correlation between preoperative PET-CT and all-cause death was observed in the patients with stage IB-IIA cervical cancer receiving surgery (aHR [95% CI]: 1.16 [0.83-1.63]; p = 0.3752). Preoperative 18FDG-PET-CT was not associated with longer survival in the patients with clinical stage IB-IIA cervical cancer receiving curative surgery.

A PET-CT Radiomics Model for Predicting Distant Metastasis in Early-Stage Non–Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiotherapy: A Multicentric Study

<h3>Purpose/Objective(s)</h3> SBRT is a guideline-recommended treatment for patients with early-stage NSCLC who are medically unfit or unwilling to undergo surgery, while some patients can still develop distant failure. The goal of this work is developing and validating a radiomics model for predicting distant failure in early-stage NSCLC patients treated with SBRT. <h3>Materials/Methods</h3> receiving SBRT were enrolled. In total, 103 CT radiomic features and 103 PET radiomic features were extracted from the pretreatment PET-CT images of each lung lesion. Patients with inoperable NSCLC treated with SBRT and have dicome format imaging available were eligible. A CT-based radiomics signature and a PET-based radiomics signature were established in one dataset and independently validated in other datasets by logistic regression after feature selection. Multivariable logistic regression analysis was then used to develop a radiomics model incorporated in the radiomics signature and independent clinical predictor. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness with internal (first center), and external (other two centers) validation. <h3>Results</h3> A total of 174 patients (with 174 lung lesions; 126, 21, and 27 from three individual institutions) were enrolled. Median follow-up was 30.7 (1.9-97.8) months. Radiomics signature was built by combining features selected from the feature pool. A model of combining CT and PET radiomic signatures with clinically significant factors like gender by logistic regression had AUC of 0.804 in the training set of first center. This model was then tested from data of first center and other two centers which showed AUC 0.785 and 0.712, respectively. <h3>Conclusion</h3> The presented radiomics model, available as an online calculator, can serve as a user-friendly tool for individualized prediction of the distant failure in early-stage NSCLC patients treated with SBRT.

Effect of Steroid Treatment on the Diagnostic Yield of Baseline PET CT in Aggressive B Cell Lymphoma

Aggressive B cell lymphomas often require prompt steroid treatment prior to baseline 18f-fluorodeoxyglucose positron-emission tomography (PET CT) scan and definitive treatment in order to alleviate symptoms and/or prevent organ damage. Since lymphomas are a steroid sensitive malignancy, there is a concern that steroid prophase might affect PET CT results and diagnostic yield.We conducted a retrospective cohort study to evaluate the effect of steroid treatment prior to baseline PET CT scan on the standardized uptake value (SUV) max and additional PET CT parameters by examining two groups of patients: steroid-naïve and steroid-treated patients. The effect of steroid administration on SUV max was examined across different daily and weekly steroid doses and durations of treatment.Between January of 2017 and May 2020, 187 newly diagnosed patients with aggressive B cell lymphoma who had a pre-treatment PET CT scan were evaluated. 160 patients (85.5%) had Diffuse large B-cell lymphoma (DLBCL)/ High-grade B-cell lymphoma, 13 patients (7%) had primary mediastinal (thymic) large B-cell lymphoma, 9 patients (4.8%) had primary DLBCL of the central nervous system and 5 patients (2.7%) had Burkitt lymphoma.132 patients (70.6%) were included in the steroid-naïve group and 55 patients (29.4%) in the steroid-treated group. In the steroid-treated group, the mean duration of steroid treatment was 10.49 (±9.28) days. Average daily dose of steroid treatment was equivalent to 72.27 (±36) mg of prednisone and the mean cumulative prednisone dose during the week prior to PET CT scan was equivalent to 367.95 (±239.9) mg of prednisone.There was no statistical significant difference between the groups in age, gender or KI67. However, patients in the steroid treated group had a significantly higher stage of disease compared to the steroid-naïve group (mean 3.44 compared to 2.99, respectively, p=0.01). The steroid-treated group also had a trend towards a higher IPI score (mean 2.45 versus 2.08, p=0.08) and a trend towards a higher LDH level (mean 2309.89 U/L, range 250-81374 versus mean 877.65 U/L, range 272-22036, p= 0.07), as depicted in table 1.There was no statistical difference in SUV max between the steroid-naïve and steroid-treated groups (p=0.97). This was consistent across various steroid treatment durations and dosage regimes. Patients in the steroid-treated group had a trend towards a higher tumor burden and a larger tumor volume compared to the steroid-naïve group, however it did not reach statistical significance. Mean tumor volume was 179.04 cm 3 in the steroid naïve group and 337.06 cm 3 in the steroid treated group (p=0.17). Mean tumor burden was 1944.84 in the steroid-naïve group and 3016.94 in the steroid-treated group (p=0.09).There was no difference in additional PET CT parameters including SUV mean, SUV max and SUV mean of liver and mediastinum between the groups as depicted in table 2.In conclusion, in aggressive B cell lymphoma, pre-treatment with steroids prior to initial PET CT scan does not affect SUV max or other PET CT parameters and does not reduce PET CT diagnostic yield. [Display omitted] DisclosuresGurion: Medison: Consultancy; Gilead Sciences: Consultancy; Takeda Pharmaceuticals: Consultancy; JC Health Care: Honoraria; Roche: Honoraria.

Posttreatment FDG-PET-CT Response via PERCIST Criteria is Predictive of Tumor Prognosis in Anal Carcinoma

We hypothesize that posttreatment F-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is useful to evaluate metabolic response in patients with anal cancer, specifically via the Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST).This was a single-institution retrospective review of 62 patients treated with Nigro Regimen chemoradiation therapy for anal squamous cell carcinoma between 2008 and 2020. All patients had pretreatment PET-CT scan and were followed with posttreatment PET-CT scans and clinical examinations. PERCIST criteria was utilized to evaluate the treatment response to chemoradiation therapy. If a target lesion shows complete resolution of FDG uptake, the response is complete metabolic response (CMR). If the decrease from baseline to follow-up is greater than or equal to 30%, the response is partial metabolic response (PMR). If the decrease is less than 30% or if the lesion shows an increase of FDG uptake less than 30%, the response is stable metabolic disease (SMD). If the target lesion shows a 30% increase or higher FDG uptake, or if there is a new lesion, the response is disease progression (DP).The median follow-up was 38 months (range, 7-114 months). Pretreatment PET-CT detected the primary tumor in 62 cases (100%), the inguinal lymph nodes were FDG avid in 33 patients, and the pelvic lymph nodes were FDG avid in 39 patients. Initial posttreatment PET-CT was obtained on average 3 months after the last day of radiation. The evaluation of the primary anal tumor on initial follow-up PET-CT showed CMR in 31 patients (50%), PMR in 26 patients (42%), and SMD in 5 patients (8%). No patients showed disease progression (DP, 0%). The evaluation of the largest inguinal node on initial post treatment PET-CT showed CMR in 30 patients (91%), PMR in 3 patients (9%), without evidence of progression of groin lymphadenopathy. The evaluation of the largest pelvic node on initial post treatment PET-CT showed CMR in 36 patients (92%), PMR in 1 patient (3%), and SMD in 2 patients (5%), without evidence of progression of pelvic lymphadenopathy.The PERCIST criteria is a reliable and useful technique in evaluating treatment response for the primary anal cancer as well as the inguinal and pelvic lymphadenopathy. The Nigro protocol is a promising combined chemoradiation therapy strategy for the anal cancer patients with most demonstrating complete metabolic response or partial metabolic response on the initial post treatment FDG PET-CT scan.

FDG-PET Utilizing Deauville Scoring Is Superior to Conventional Imaging for Staging and Response Assessment in Pediatric and Adult Patients with Nodular Lymphocyte Predominant Hodgkin's Lymphoma

Introduction:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding FDG-PET-CT scan (PET-CT) use in NLPHL. We are reporting our experience with PET-CT utility in staging and response assessment of patients with NLPHL and compare this with conventional contrast enhanced CT scan (CT).Methods:Using prospectively collected lymphoma data base and Hospital Tumor Registry, all pediatrics and adult patients with NLPHL seen at our institution from 2003 to 2016 were captured. Patients who underwent pre-treatment CT and PET-CT, during the course of chemotherapy, at the end of planned treatment or for relapsed /refractory disease prior to have new treatment were included in this study. PET-CT response was assessed using both visual assessment method (mediastinal blood pool activity was used as a reference for normal uptake) and Deauville criteria. Both methods were compared (5-point Deauville Criteria; a score of 1-3 as negative-disease and 4-5 as positive-disease).ResultsWe identified 67 NLPHL who met the inclusion criteria. Median age at diagnosis was 27 years (6-56 years) and median follow-up was 30.7 months (5.95-157.4) with a male: female ratio of 4.1:1. Median SUV-max was 8.8 (2.0 to 18.8). In 30 pediatrics patients (age <21 years), median SUV-max was 8.7 (4.0 to 18.8).In the per-scan analysis, the sensitivity, specificity and positive predictive value of pre-treatment PET-CT was 100 %, 99% and 98% respectively. Among the total of 79 pre-therapeutic PET-CT, 948 sites were analyzed, 238 sites were true-positive (1 bone/3 bone marrow involvement, 4 parotids, 4 nasopharynx, 3 liver, 2 lungs, and 221 nodal involvement), 5 were false positive (4 were progressive transformation of germinal center and 1 was reactive lymph node) and 705 sites were true negative. In 5 patients, PET-CT revealed extra nodal disease that was subsequently confirmed on follow-up, but was not picked by CT. There was an agreement between the CT and the PET-CT staging in 68 scans (86%). The staging was changed in 11 (14%) patients; 8 (10%) were upstaged (7 nodal and 1 bone marrow) and 3 (4%) were down staged by PET-CT.A total of 33 bone marrow biopsies (BMBx) were performed and PET-CT confirmed all BMBx results (32 BMBx negative and PET-CT negative, 1 patient BMBx positive and PET-CT positive) showing 100% concordance and suggesting a positive PET-CT for bone or bone marrow is adequate to designate advanced stage. In 2 patients, pre-therapeutic PET-CT revealed bone marrow involvement that was unsuspected before the PET-CT examination.A total of 83 end of treatment PET-CT were carried out, 72 scans were negative (score 1-3) and 11 scans were positive (score 4-5). Treatment consisted of local treatment in the form of surgery/radiation in 7 patients, 2-4 cycles of ABVD +/- radiotherapy in 43 patients, and 6-8 cycles of ABVD +/- radiotherapy in 17 patients. Of the 238 previously involved sites, 204 became true negative, 31 remained true positive, and 3 sites had false negative results with no false positives, showing the negative predictive value of 98.6% with specificity of 100%. Deauville criteria correlated very well with visual assessment criteria. 83 post treatment CT scans showed that out of 238 previously involved sites, 180 became true negative, 24 sites were false positive with specificity of 88%. Two year progression free survival of the entire cohort was 83%.Twenty one patients with stage II, III and IV patients whom were planned to receive 6-8 cycles of chemotherapy underwent mid-treatment PET-CT that were assessed based on Deauville Criteria. 13 patients had negative-disease with none failed primary treatment. 8 had positive-disease; out of which 4 failed primary treatment (numbers are too small for statistics) (Table1).Conclusion:Our data suggest that baseline PET scan is far superior to CT staging. A negative pre-therapy PET-CT for bone/bone marrow is sufficient to omit BMBx. Mid-treatment PET-CT response may have a prognostic role. The validity of the Deauville Score for interpretation of the end of treatment response assessment scans in adult and pediatric patients has been confirmed by the present study. PET-CT has much better specificity for response assessment than CT. Deauville criteria are in concordance with visual assessment criteria and can be applied in real practice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Old Drugs with New Tricks: Rituximab in Combination with Albumin-Bound paclitaxel and Pegylated Liposomal Doxorubicin in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

▪There is great unmet need in improving the prognosis of patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). How to get those patients into remission and enable them to receive autologous stem cell transplantation (ASCT) is a great challenge. A phase 2 clinical trial was conducted to evaluate the efficacy and safety of rituximab in combination with albumin-bound paclitaxel and pegylated liposomal doxorubicin (RAD) in patients with relapsed/refractory DLBCL who received at least two prior lines of immunochemotherapy (ChiCTR-OIC-16008700,http://www.chictr.org.cn). 13 patients were enrolled with a median age of 40 years. All patients received a median of 3 prior lines of therapy. 12 patients received at least two cycles of RAD. After 2 cycles of RAD, the complete response rate was 38.5%, partial response rate was 46.2%, and overall response rate was 84.6%. Three patients successfully received subsequent ASCT, and were still alive without disease after a follow-up time of 6 months, 19 months, and 33 months, respectively. Three patients died of disease progression when waiting for ASCT, and another three patients failed collection of stem cells due to bone marrow dysfunction. This RAD regimen was well tolerated with mostly reported adverse events being grade 2 or 3 hematologic events. In conclusion, we demonstrated that rituximab in combination with albumin-bound paclitaxel and pegylated liposomal doxorubicin was highly active in patients with relapsed/refractory DLBCL, and this regimen should be considered as an effective salvage therapy to bridge subsequent ASCT.Figure 1. Comparison of pre-treatment and post-treatment PET-CT scan in one relapsed/refractory DLBCL patient. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A cross-sectional analysis of muscle density and physical function in head and neck cancer patients.

e18597 Background: Head and neck cancer (HNC) is a debilitating disease that affects tens of thousands each year and both the disease and its treatment can cause long-term morbidity. HNC patients with greater physical function at baseline may better withstand both disease and treatment, therefore we hypothesized that baseline physical function is associated with baseline skeletal muscle density (SMD). Methods: A cross-sectional study of existing medical records was conducted. SMD was classified using pre-treatment PET-CT scans and interpreted using Sliceomatic software, and pre-treatment physical function assessed in three ways: hand grip strength, timed up and go, and short physical performance battery. Linear regression models were utilized to assess the association between SMD and each measure of physical function, with adjustment for muscle mass, sex and cancer stage in the hand grip strength model and adjustment for muscle mass and age in both the timed up and go, and short physical performance battery models. Results: The sample of 90 HNC patients, was mostly white, male, former smokers with an average BMI of 28 kg/m2. In adjusted models that included men only, we observed that for every Hounsfield unit increase in SMD there was a 0.08 increase in SPPB score (p=0.005), a 0.31 kg increase in hand grip strength (p=0.04), and a 0.13 second decrease in timed up and go (p=0.0007). In adjusted models that included women only, we observed that for every Hounsfield unit increase in SMD there was a 0.03 decrease in SPPB score (p=0.75), a 0.12 kg increase in hand grip strength (p=0.65), and a 0.01 second increase in timed up and go (p=0.84). Conclusions: Baseline physical function is associated with higher baseline physical SMD. Larger studies involving a more women are needed to replicate these findings and to further examine the potential role of effect modification by both sex and muscle mass.

Machine learning-based FDG PET-CT radiomics for outcome prediction in larynx and hypopharynx squamous cell carcinoma

To determine whether machine learning-based radiomic feature analysis of baseline integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) computed tomography (CT) predicts disease progression in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (SCC) receiving (chemo)radiotherapy. Patients with larynx and hypopharynx SCC treated with definitive (chemo)radiotherapy at a specialist cancer centre undergoing pre-treatment PET-CT between 2008 and 2017 were included. Tumour segmentation and radiomic analysis was performed using LIFEx software (University of Paris-Saclay, France). Data were assigned into training (80%) and validation (20%) cohorts adhering to TRIPOD guidelines. A random forest classifier was created for four predictive models using features determined by recursive feature elimination: (A) PET, (B) CT, (C) clinical, and (D) combined PET-CT parameters. Model performance was assessed using area under the curve (AUC) receiver operating characteristic (ROC) analysis. Seventy-two patients (40 hypopharynx 32 larynx tumours) were included, mean age 61 (range 41-77) years, 50 (69%) were men. Forty-five (62.5%) had chemoradiotherapy, 27 (37.5%) had radiotherapy alone. Median follow-up 26 months (range 12-105 months). Twenty-seven (37.5%) patients progressed within 12 months. ROC AUC for models A, B, C, and D were 0.91, 0.94, 0.88, and 0.93 in training and 0.82, 0.72, 0.70, and 0.94 in validation cohorts. Parameters in model D were metabolic tumour volume (MTV), maximum CT value, minimum standardized uptake value (SUVmin), grey-level zone length matrix (GLZLM) small-zone low grey-level emphasis (SZLGE) and histogram kurtosis. FDG PET-CT derived radiomic features are potential predictors of early disease progression in patients with locally advanced larynx and hypopharynx SCC.

Prediction of survival outcome based on clinical features and pretreatment 18FDG-PET/CT for HNSCC patients

Background and objectiveIn this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH). MethodsWe have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics. ResultsIt is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%. ConclusionsThe proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient’s outcome, and depending upon the outcome treatment policy can be selected.

Prognostic significance of adipose tissue distribution and metabolic activity in PET-CT images of patients with metastatic colorectal cancer.

e16038 Background: The metabolic activity in visceral and subcutaneous adipose tissue have different metabolic risk profiles for colorectal cancer. The aim of this study was to investigate the prognostic significance of adipose tıssue distribution and metabolic activity in PET-CT and predict the overall survival in patients with metastatic colorectal cancer (mCRC). Methods: A total of 83 patients diagnosed with mCRC between 2010-2018 were evaluated retrospectively. Pretreatment PET-CT images were reevaluated to determine adipose tissue distribution and metabolic activity. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET-CT images were measured. SAT volume, SAT density (HU), SAT ratio (SAT volume/ SAT density) were calculated. The maximum standardized uptake (SUV) of tumor tissue was measured. The relationship between adipose tissue and overall survival was examined. Results: 53 patients died during follow-up and the median overall survival was 33.76 months (95% CI: 28.185-39.349). According to univariate analysis results, tumor location (HR:2.5; 95% CI 1.27-4.98, p = 0.008) and SAT ratio (HR:0.5; 95% CI 0.34-1.00, p = 0.053) were the significant parameters for the OAS. VAT volume (p = 0.774), VAT density (p = 0.899), VAT suv mean (p = 0.831) and SAT volume (p = 0.423), SAT density (p = 0.353), SAT suv mean (p = 0.575), tumor suv max (p = 0.589) values were not correlated with OAS. In the multivariate analysis, SAT ratio (p = 0.011) and tumor location (p = 0.001) were correlated significantly with OAS. The median OAS for the patients with SAT ratio value &lt; -1.1 and -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). Conclusions: This study showed that SAT ratio was an independent prognostic factor for OAS in patients with mCRC. We need prospective studies for to observe the relationship between adipose tissue distribution and response to treatment in mCRC.

Comparison between body composition parameters and response to neoadjuvant chemotherapy by using pre-treatment PET CT in locally advanced breast cancer

PurposeTo compare the adipose and muscle tissue areas in patients who responded differently to neoadjuvant chemotherapy. MethodsOne hundred and eighty six patients diagnosed with breast cancer who underwent neoadjuvant chemotherapy between January 2015- October 2019 and were operated after the treatment were retrospectively included in the study. Pathological results were divided into five groups using the Miller-Payne grading systems. Grade 1 indicating no significant reduction in malignant cells; Grade 2: a minor loss of malignant cells (≤ 30 %); Grade 3: reduction in malignant cells between 30 % and 90 %; Grade 4: disappearance of malignant cells >90 %; Grade 5: no malignant cells identifiable. Pre-treatment PET CT scans were evaluated, and calculation of body composition parameters were performed on a single axial section passing through the L3 vertebrae. Spearman’s correlation test was used to analyze the correlation between SAT, VAT, MT parameters and pathological responses. ResultsThere was no strong correlation between the 5 groups separated according to neoadjuvant chemotherapy treatment response and tissue distributions. However, that there was a very low correlation found between superficial adipose tissue and pathological response (r=, 156). ConclusionIn conclusion, our results have provided a very low correlation between SAT and more than 30 % response. More research is required to evaluate the role of the body fat and muscle parameters in response to neoadjuvant chemotherapy in larger patient populations.

Deep segmentation networks predict survival of non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) represents approximately 80–85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography/computed tomography (PET/CT) images have predictive power for NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for NSCLC prognostication, but their prognostic value remains controversial. Meanwhile, convolutional neural networks (CNN) are rapidly emerging as a new method for cancer image analysis, with significantly enhanced predictive power compared to hand-crafted radiomics features. Here we show that CNNs trained to perform the tumor segmentation task, with no other information than physician contours, identify a rich set of survival-related image features with remarkable prognostic value. In a retrospective study on pre-treatment PET-CT images of 96 NSCLC patients before stereotactic-body radiotherapy (SBRT), we found that the CNN segmentation algorithm (U-Net) trained for tumor segmentation in PET and CT images, contained features having strong correlation with 2- and 5-year overall and disease-specific survivals. The U-Net algorithm has not seen any other clinical information (e.g. survival, age, smoking history, etc.) than the images and the corresponding tumor contours provided by physicians. In addition, we observed the same trend by validating the U-Net features against an extramural data set provided by Stanford Cancer Institute. Furthermore, through visualization of the U-Net, we also found convincing evidence that the regions of metastasis and recurrence appear to match with the regions where the U-Net features identified patterns that predicted higher likelihoods of death. We anticipate our findings will be a starting point for more sophisticated non-intrusive patient specific cancer prognosis determination. For example, the deep learned PET/CT features can not only predict survival but also visualize high-risk regions within or adjacent to the primary tumor and hence potentially impact therapeutic outcomes by optimal selection of therapeutic strategy or first-line therapy adjustment.

Redistribution of Cervix Cancer Patients from FIGO 2009 to FIGO 2018 Staging Following Incorporation of Medical Imaging

Objectives: The aim of this study was to quantify the shift in patients from the FIGO 2009 to the FIGO 2018 staging using a prospectively collected dataset where pre-treatment MRI and PET-CT were used. A secondary aim was to explore the distribution of known prognostic factors in both staging schema. Methods: Prospectively collected dataset of 1047 cervix cancer patients staged with MRI and PET-CT, between 1996 and 2014, were redistributed using FIGO 2018 staging criteria. Standard deviation inter-quartile and contingency tables were used to present the distribution of patients according to FIGO 2009 and FIGO 2018 criteria. Logistic regression was used to evaluate the association of node positivity and nodal size. Results and Discussion: In total, 853 patients were available for analyses. Based on MRI and PET findings, according to FIGO 2009, the incidence of lymph node metastasis was similar in (1) stages 1b1 and 2a1, (2) 1b, 2a2, 2b and 3a (3) 3b and 4a. Nodal metastases were found in 43% patients who were upstaged from FIGO 2009 to newly created FIGO 2018 stages 3c1 and 3c2. Contribution to stage 3c1 came from 31, 41, 29, 30, 32, 33 and 34% of stages 1b1, 1b2, 2a1, 2a2, 3a and 3b, respectively. FIGO 2009 stages 1b1 and 1b2 contributed 5 and 6%, stages 2a1, 2a2, 2b and 3a contributed 16, 15 and 15% to para-aortic nodes, while stage 3b contributed 24%. These findings will likely influence cervix cancer treatment policies.

Stage Migration in Cervical Cancer Using the FIGO 2018 Staging System: A Retrospective Survival Analysis Using a Single Institution Patient Cohort. Is There a Will Rogers Phenomenon?

The FIGO staging system for cervical cancer was modified in 2018, allowing the use of cross-sectional imaging for staging purposes. Stage IB is now divided into 3 instead of 2 substages, based upon the size of tumor: IB1 < 2 cm, IB2 two to 4 cm, and IB3 > 4 cm. Detection of lymph nodes in the pelvis or para-aortic region now upstages lower stages to IIIC. The purpose of this study was to evaluate the extent of stage migration with the FIGO 2018 staging system for cervical cancer and retrospectively validate the new staging system using our institution’s patient cohort. With IRB approval, we reviewed 158 patients with cervical cancer diagnosed between 2010 and 2018 at our institution. The patients had been staged according to the FIGO 2009 staging system. Data regarding the size of the tumor and the presence of lymph nodes and/or metastatic disease in the pretreatment CT, PET-CT, or MRI scans were collected. Patients were restaged using the FIGO 2018 system and we evaluated the extent of stage migration with the new staging system. For validation, we analyzed the 3-year overall survival (OS) by both FIGO 2009 and 2018 staging systems. Kaplan Meier analyses were performed using statistical analysis software. Fifty-nine percent of the patients were upstaged when the FIGO 2018 staging system was used. In the new 2018 staging system, Stage IB3 accounted for only 4% while Stage IIIC accounted for 48% of the patient cohort. The median OS of the entire cohort was 20.5 months. There were changes in the survival curves comparing FIGO 2018 to FIGO 2009; however, there were no statistically significant differences in 3-year OS, our primary endpoint (Table 1), perhaps due to insufficient number of patients in each stage. Interestingly, the 3-year OS of Stage IIIC patients was better compared to Stages IIIA & B combined (61% vs. 25%, p=0.017). This is likely secondary to greater local tumor extent contributing to the poorer outcomes that nodal metastasis in lower stage disease. The increased availability of cross-sectional imaging across the world has led to its permissibility in the FIGO staging system for cervical cancer. We identified a significant stage migration in our patient cohort when using the FIGO 2018 staging system. However, statistically significant differences in the 3-year OS were not detected. A larger patient cohort may answer some of the questions raised by this hypothesis-generating study. FIGO (2009) FIGO (2018)Abstract 2776; Table 1StageFrequency3- year OSFrequency3-year OSP valueI B31 (20%)83%21 (13%)94%0.4II52 (33 %)62 %21 (13%)59 %0.6III45 (28%)53 %84 (53%)57%0.6IV A12 (8 %)33 %12 (8%)33%1.0IV B18 (11%)020 (13%)0158 (100%)158 (100%) Open table in a new tab

Metabolic Trending during SBRT for Central Lung Oligomets!

SBRT, predominantly, causes indirect cell kill through (1) Vascular apoptosis, starts few hrs after treatment peaking at 3 days and (2) immunological alteration in the tumor microenvironment, process which starts around 3 days & peaks at 10-12 days. Routine Post SBRT metabolic imaging is advised at 3 months. Present study evaluates clinical response of multifraction SBRT during and post-treatment completion with serial FDG PET-CT scans in patients with solitary central lung oligometastases. Five patients with oligometastatic central lung tumors (Primaries: breast - 3, colorectal - 1, and kidney-1) underwent SBRT by DIBH technique using ABC on 6 DOF C-arm Linac using body fix immobilization. Peripheral lesions were excluded from this study (as fractionation protocols ranges from 1-3). A risk adapted multi-fractionated protocol – 6 Gy x 8 fractions was used for treatment delivery. All patients underwent limited metabolic imaging pre-treatment, during treatment, and post-treatment PET-CT scans up to 3mos. During treatment PET-CT imaging after delivery of 3 fractions or at least after 18 Gy dose delivery. Post SBRT serial PET-CTs scans were timed serially at 48hrs, 10 days, 30 days and 60 and 90 days post treatment. PET-CT images were reviewed in order to determine the pre-treatment, during treatment, and post-treatment maximum standardized uptake value (m-SUV) of the lesion, including “complete resolution” of FDG-avidity. Corresponding Morphologic variations of the target lesions were studied on the CT images during the 3-mo. evaluation period. All the 5 patients showed nearly consistent serial regression in metabolic activity during the treatment. The observed metabolic regression was between 60%-65% (median 50%%) after 3 frcs/ 18gy dose scan, 80% (median – 70%) after delivery of 6 frcs/ post-32gy dose scan and 80% (median 80%) at 48hrs post treatment scans, 85-90 % (median - 90%) 10 days post SBRT. After the 10th day Scan, SUV thereupon remained constant ranging between 1.3 - 3.2 (median 2.3) up to 3 months. The earliest morphologic changes on CT in the form of ground glass appearance was detected at 60 days post SBRT scan uniformly in all patients. During the evaluation period (first 3 months) there was no significant change in size of the lesion. The metabolic response precedes morphologic response, with an early metabolic response seen immediately after 24 Gy dose delivery & maximum metabolic response seen at 10 days post SBRT. This is the first study reported in literature which looked into the serial metabolic trending during Lung SBRT for central lesions.

Pretreatment SUVmax value to predict outcome in patients with stage III NSCLC receiving concurrent chemoradiotherapy.

OBJECTIVE:Stage III disease accounts for approximately one-fourth of all non-metastatic non-small cell lung cancer (NSCLC). The patients who are not candidates for curative resection are offered concomitant chemoradiotherapy. In this subgroup, which is difficult to manage, studies that address the role of PET-CT to predict outcome measures specifically for stage III NSCLC receiving concurrent chemoradiotherapy may help better risk stratification. This study aimed to assess whether baseline PET maximum standardized uptake value (SUVmax) value in stage III NSCLC treated with concurrent chemoradiotherapy would independently identify patients with high risk of progression and death.METHODS:The study population consisted of patients aged 18 years or more with unresectable stage III histologically or cytologically proven NSCLC who received concurrent chemoradiotherapy. From 2007 to 2014, medical records of patients admitted to our institution were retrospectively analyzed. Pretreatment PET-CT SUVmax values were recorded for each patient. These values were categorized as low or high according to the median SUVmax measure of the study population.RESULTS:A total of 175 patients were analyzed. The median follow-up time was 23 months (range 6–109). The PET-CT SUVmax values ranged from 3.5 to 46 with a median value of 14. The median overall survival was 25 months in SUVmax <14 and 18 months in SUVmax ≥14 group (p=0.023). The median progression-free survival was 16 months in SUVmax <14 and 11 months in SUVmax ≥14 group (p=0.033). Multivariate analysis revealed that both PET-CT SUVmax value (p<0.001) and age (p=0.016) were independent significant predictors for overall survival (OS).CONCLUSION:The results of this study involving patients with stage III NSCLC receiving concurrent chemoradiotherapy provide evidence that suggests that high values of pretreatment SUVmax, an indicator of metabolic tumor burden, predicted a higher risk of disease progression and death.