The aim of this initiative was to provide consensus recommendations from a consortium of academic and industry experts in the field of lymphoma and imaging for the consistent application of imaging assessment with the Lugano classification. Methods: Consensus was obtained through a series of meetings from July 2019 to October 2021 sponsored by the PINTaD (Pharma Imaging Network for Therapeutics and Diagnostics) as part of the ProLoG (PINTaD RespOnse criteria in Lymphoma wOrking Group) consensus initiative. Results: Consensus recommendations encompass all technical imaging aspects of the Lugano classification. Some technical considerations for PET/CT and diagnostic CT are clarified with regards to required imaging series and scan visits, as well as acquisition and reconstruction of PET images and influence of lesion size and background activity. Recommendations are given on the role of imaging and clinical reviewers as well as on training and monitoring. Finally, an example template of an imaging case report form is provided to support efficient collection of data with Lugano Classification. Conclusion: Consensus recommendations are made to comprehensively address technical and imaging areas of inconsistency and ambiguity in the classification encountered by end users. Such guidance should be used to support standardized acquisition and evaluation with the Lugano 2014.

Background Zr-Df-Crefmirlimab is a humanized, engineered, 80-kDa minibody (an antibody fragment), with high affinity to human CD8 (kd of 0.4 nM). It has been evaluated as an imaging agent in a Phase-II open-label multi-dose study (NCT03802123) in patients with metastatic solid malignancies (figure 1) scheduled to receive standard of care immunotherapy (Nivolumab, Pembrolizumab and Ipilimumab-Nivolumab). Supervised machine learning (ML) combined with tumor growth-inhibition (TGI) modeling was applied to predict clinical response using various baseline patient characteristics including CD8 density (via biopsy) and CD8 PET imaging SUV (Standardized Uptake Value). Methods Modeling framework for prediction of response to immunotherapy was developed leveraging multimodal data (figure 2) including CD8 PET imaging readouts. Random forest was used for classification of response using only baseline characteristics from 32 patients. Data was randomly assigned into training and test data (65:35). Performance of the model on test data was evaluated using area under the receiver operating characteristic curve (ROC AUC). Rates of tumor growth and kill were estimated from a TGI model developed using early tumor kinetic data (first three time points). Baseline CD8 density and SUV were used along with estimated TGI model parameters to classify patient response using supervised ML. Explainable ML techniques like partial dependence and individual conditional expectation were leveraged to further explore contribution of features of interest towards model outcome. Results Using only baseline characteristics, AUC of 0.75 was achieved on the test data with an overall prediction accuracy of 82%. Using partial dependence of model features, increase in the likelihood of patient response was observed with increasing CD8 density and SUV at baseline. Early tumor kinetic data was described reasonably well by the developed TGI model. AUC of 0.88 was achieved on the same test data (as above) with an overall prediction accuracy of 91% using individual estimates of tumor growth and kill from the TGI model and baseline CD8 density and SUV. Decrease in likelihood of response was associated with increasing rate of tumor growth and smaller baseline CD8 density. Conclusions Baseline CD8 density and PET SUV data were used along with other patient characteristics to predict clinical outcome to immunotherapy with a reasonable degree of accuracy. Using a combined approach of tumor growth inhibition modelling and supervised machine learning, high precision in prediction of clinical outcome was achieved leveraging baseline CD8 PET information and early tumor kinetic data.

Our objective was to provide consensus recommendations from a consortium of academic and industry experts in the field of lymphoma and imaging for consistent application of the Lugano classification. Methods: Consensus was obtained through a series of meetings from July 2019 until September 2021 sponsored by the Pharma Imaging Network for Therapeutics and Diagnostics (PINTaD) as part of the PINTaD Response Criteria in Lymphoma Working Group (PRoLoG) consensus initiative. Results: Consensus recommendations clarified technical considerations for PET/CT and diagnostic CT from the Lugano classification, including updating the FDG avidity of different lymphoma entities, clarifying the response nomenclature, and refining lesion classification and scoring, especially with regard to scores 4 and 5 and the X category of the 5-point scale. Combination of metabolic and anatomic responses is clarified, as well as response assessment in cases of discordant or missing evaluations. Use of clinical data in the classification, especially the requirement for bone marrow assessment, is further updated on the basis of lymphoma entities. Clarification is provided with regard to spleen and liver measurements and evaluation, as well as nodal response. Conclusion: Consensus recommendations are made to comprehensively address areas of inconsistency and ambiguity in the classification encountered during response evaluation by end users, and such guidance should be used as a companion to the 2014 Lugano classification.

e19517 Background: iwCLL 2018 criteria defines liver enlargement as one of the important group A parameters for staging and overall response assessment (ORA). However, the authors acknowledge that given the impact of numerous medical conditions, liver size by physical examination or CT scan is not a reliable measure of hepatic involvement by CLL and should only be considered if hepatomegaly is clearly attributable to lymphoid involvement. The criteria even define partial response and progression categories as 50% decrease or increase, respectively, but no specific size or other criteria for assessing lymphoid involvement are proposed. Focal lesions in liver may be a sign of involvement by CLL but are assessed separately, as extranodal disease. Hepatomegaly may be non-specific with possible causes including metabolic, infectious, neoplastic, toxic, hereditary, vascular, and miscellaneous other causes. 20-30% of a general population may have non-alcoholic fatty liver enlargement. In the literature hepatomegaly by palpation has been defined as a portion of the liver below the costal margin and the cut-off for normal liver on imaging is considered < 16 cm in mid-clavicular line. However, there are various anatomic variations with no consensus on the size criteria for liver enlargement. Methods: Independent review data from seven phase II/III CLL trials for frontline therapies as well as in relapsed/refractory setting, were retrospectively analyzed. Data included the independent review assessment results of a total of 22224 timepoints (TPs) of 2223 subjects (2223 baseline (BL) and 20001 post-BL TPs). The data were analyzed for the incidence of subjects with liver enlargement at baseline, post-BL assessment of liver and its impact on ORA. Liver assessment in all trials was qualitative, and the criteria for enlargement was based on the reviewer’s judgement; no size limit was defined. Results: Only 7 out of 2223 subjects (0.3%) had liver enlargement at baseline. Liver assessment of these subjects at post-BL did not cause an upgrade or downgrade of the ORA. None of the 2223 subjects had liver progression at post-BL TPs. Conclusions: Based on the data analysis of a large sample size, it is evident that assessment of liver enlargement as a group A parameter in CLL clinical trials, does not impact the ORA. Liver is rarely even assessed as enlarged by independent reviewers, since hepatomegaly may be caused by various other medical conditions besides CLL. No size or other criteria help distinguish between liver enlargement from CLL versus other causes. We recommend removing liver enlargement as a group A parameter for response assessment as it complicates the assessment paradigm without adding any value to it. Liver involvement should only be assessed for focal lesions, as extranodal disease.

Background The landscape of imaging in multiple myeloma has changed drastically since the publication of IMWG 2016 criteria. 18 F-FDG PET-CT (PET-CT) is being used more frequently, for staging, prognosis and clinical decision making. PET-CT is useful for both morphological and the metabolic activity of the plasma cells to predict and monitor clinical response. Studies have shown that subjects who achieved complete response by hematologic criteria but have PET positive lesions have poorer outcome. PET-CT has high sensitivity and specificity for detecting all lesions types. PET negativity has been equated to Minimal residual disease (MRD) negativity, and hence role of both positive and negative PET in IMWG response assessment need to be better defined. Until now extramedullary disease (EMD) and plasmacytoma evaluation have been the focus of response assessment in IMWG, although plasmacytoma is a histological, not an imaging diagnosis. Paramedullary lesions (lytic bone lesions with extraosseous soft tissue component), intramedullary lesions (soft tissue lesions in the medullary cavity) as well as pure lytic bone lesions have not been fully included in the evaluation. There is a need to better define various lesions and disease presentations seen on imaging in myeloma and their role in overall response. Additionally, role of different imaging modalities in clinical trials as well as a standardized imaging schedule, based on the presence of baseline disease burden, should be defined. The purpose of this study is to define and incorporate the imaging manifestations of myeloma of PET-CT into the IMWG criteria. A standardized PET-CT assessment approach is lacking in IMWG 2016, although Italian Myeloma Criteria for PET Use (IMPeTUs), has described PET-CT evaluation in detail, including the cut off for positivity and negativity, aligning it to 5-point Deauville Scoring (5PS). This study will also highlight the importance of PET-CT as a modality of choice in myeloma and provide a standardized methodology to integrate PET in overall assessment. We propose that myeloma lesions should be assessed in two broad categories, target (measurable) and non-target (non-measurable) lesions. Targets should include up to a total of six extramedullary and/or paramedullary lesions. Non-target lesions should include any additional measurable lesions, other soft tissue and bone lesions characteristic of myeloma, which do not meet criteria for target lesions. The status of these lesions along with any new lesions will drive an overall anatomical response. For PET-CT assessments, 5PS should be followed with liver as comparator for positivity. Metabolic responses like Complete metabolic response(CMR) etc. should be derived. An integrated imaging response can then be combined with clinical parameters to provide an overall IMWG response. This proposed guidance will help standardize integration of PET imaging in IMWG response assessment more efficiently and consistently across trials. The landscape of imaging in multiple myeloma has changed drastically since the publication of IMWG 2016 criteria. 18 F-FDG PET-CT (PET-CT) is being used more frequently, for staging, prognosis and clinical decision making. PET-CT is useful for both morphological and the metabolic activity of the plasma cells to predict and monitor clinical response. Studies have shown that subjects who achieved complete response by hematologic criteria but have PET positive lesions have poorer outcome. PET-CT has high sensitivity and specificity for detecting all lesions types. PET negativity has been equated to Minimal residual disease (MRD) negativity, and hence role of both positive and negative PET in IMWG response assessment need to be better defined. Until now extramedullary disease (EMD) and plasmacytoma evaluation have been the focus of response assessment in IMWG, although plasmacytoma is a histological, not an imaging diagnosis. Paramedullary lesions (lytic bone lesions with extraosseous soft tissue component), intramedullary lesions (soft tissue lesions in the medullary cavity) as well as pure lytic bone lesions have not been fully included in the evaluation. There is a need to better define various lesions and disease presentations seen on imaging in myeloma and their role in overall response. Additionally, role of different imaging modalities in clinical trials as well as a standardized imaging schedule, based on the presence of baseline disease burden, should be defined. The purpose of this study is to define and incorporate the imaging manifestations of myeloma of PET-CT into the IMWG criteria. A standardized PET-CT assessment approach is lacking in IMWG 2016, although Italian Myeloma Criteria for PET Use (IMPeTUs), has described PET-CT evaluation in detail, including the cut off for positivity and negativity, aligning it to 5-point Deauville Scoring (5PS). This study will also highlight the importance of PET-CT as a modality of choice in myeloma and provide a standardized methodology to integrate PET in overall assessment. We propose that myeloma lesions should be assessed in two broad categories, target (measurable) and non-target (non-measurable) lesions. Targets should include up to a total of six extramedullary and/or paramedullary lesions. Non-target lesions should include any additional measurable lesions, other soft tissue and bone lesions characteristic of myeloma, which do not meet criteria for target lesions. The status of these lesions along with any new lesions will drive an overall anatomical response. For PET-CT assessments, 5PS should be followed with liver as comparator for positivity. Metabolic responses like Complete metabolic response(CMR) etc. should be derived. An integrated imaging response can then be combined with clinical parameters to provide an overall IMWG response. This proposed guidance will help standardize integration of PET imaging in IMWG response assessment more efficiently and consistently across trials.

e19522 Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma with over 18,000 new cases diagnosed each year in the United States and approximately 7-8 cases per 100.000 people globally. Hodgkin’s Lymphoma (HL) is less common accounting for approximately 9,000 new cases each year. However, their imaging manifestations overlap; with both the diseases demonstrating extensive lymph nodal and extra-nodal involvement along with intense uptake on 18 FDG-PET. Novel targeted therapies have been developed to improve survival in patients with DLBCL and HL. The purpose of this study analysis was to determine if there was a correlation between the baseline tumor burden and early tumor progression based on imaging. Methods: This retrospective study involved the analysis of baseline imaging data (CT, MRI and PET) of 469 patients enrolled in multiple phase II/III clinical trials involving a diagnosis of DLBCL and HL. Image analysis was performed utilizing the IWG criteria Lugano 2014 modification. The staging of the baseline disease burden was performed as per the Revised Staging System for Primary Nodal Lymphomas. In addition to the staging, the sum of the product of perpendicular diameters of all target lesions (SPD), and spleen size at baseline were recorded. The time point of disease progression was also captured in this analysis for each patient. These baseline imaging parameters were compared among patients with early progression (≤6 months following onset of therapy). Results: Out of the 469 patients, 61.4% of patients (n = 288/469) demonstrated disease progression during treatment and/or follow up phase of the trial. In this cohort, 64.5% (n = 186/288) of patients showed early progression. Patients with advanced stage disease at baseline (Stage II bulky, III and IV) showed a higher rate of early progression compared to those with limited baseline disease burden (Stage I and II) (47.1% vs 32.9%). The occurrence of early progression was similar in patients with normal spleen size at baseline compared to those with an enlarged spleen at baseline (39.3% vs 41%). There was a trend towards higher baseline SPD in patients with early progression (3204mm 2 , +12.5%) and late progression (3185mm 2 , +12%) compared to patients who did not demonstrate progression during the trial phase (2804mm 2 , p = 0.23-0.45). Conclusions: Baseline disease staging is an important determinant of early progression in patients with DLBCL and HL. Baseline tumor burden is potentially a predictive marker of disease progression. Therefore, precise staging along with accurate recording of baseline tumor burden have important prognostic and subsequent therapeutic strategy implications for prospective decision making in the era of precision medicine. Further prospective studies may be needed to validate our results.

e13557 Background: Lung cancer is the leading cause of cancer death in the world including more than 160,000 deaths in the US. The purpose of the study was to determine whether inter reader variability in Sum of Diameters (SOD) of tumor burden has any correlation with variability in end point assessment in lung cancer progression. RECIST 1.1 is based on the SOD of target lesions seen on imaging studies. Response criteria for evaluation of target lesions include - Complete response (CR), Partial response (PR), Progressive disease (PD) and Stable disease (SD). The key determinant of patient response is based on Target Lesion response which in turn is determined by SOD. Inter reader variability study plays an important role in the development of reliable diagnostic tools and understanding of imaging outcomes given the confounding factors like effusion, atelectasis and consolidation in lung cancer that affect Target Lesion selection. Methods: Retrospective analysis of 470 patients was carried out using RECIST 1.1. Double read with adjudication is the preferred read model for submission studies where images are read by two independent reviewers blinded to treatment allocation. As per RECIST 1.1, lesions were measured in the longest diameter for non-nodal and short axis for nodal lesions. This was followed by the calculation of SOD for total tumor burden. If these two primary reviewers disagree, then a third radiologist, the “adjudicator”, reviews the assessments performed by the first two radiologists and selects between the more accurate one. For further analysis, patients were divided into 2 groups, the one with no adjudication i.e. agreement between both readers and the second group with adjudication i.e. disagreement between both readers and ANOVA was used to perform analysis of Variance. Results: Of 470 patients, 332 patients with disagreement were adjudicated, while there was agreement on 138 patients assessments between both readers. SOD of baseline visits for all patients was assessed using ANOVA - single factor with following results: F ratio of 4.76 for Disagreement group was more than F crit (3.86) with P-value 0.03, while for Agreement group F value was less than F crit. Conclusions: There is a direct relationship of variability in SOD at baseline between two readers to the possibility of disagreement in their end point assessment. Additional rules around selection and measurement of Target Lesions should be proposed in protocol to reduce variability and improve endpoint assessment outcomes.[Table: see text]

e19502 Background: In trials with BTKi, lymphocytosis alone may not be a sign of progression but rather treatment related redistribution of lymphocytes from tissues into the peripheral blood (Cheson et al 2012). This observation was later incorporated in iwCLL 2018 criteria. However, no clear details were provided on how to assess lymphocytosis along with other parameters to derive an overall timepoint response (OTR) in a clinical trial setting. While PRL is a response category used to assess lymphocytosis in many clinical trials, it has not been defined in iwCLL 2018. Furthermore, iwCLL 2018 defines Absolute Lymphocyte Count (ALC) progression (PD) as an increase of ALC ≥ 50% compared to baseline whereas conventionally progression is defined in comparison to nadir, which may lead to under reporting of ALC PD. Methods: Data from multiple (8) phase II/III CLL trials with BTKi (frontline and relapsed/refractory setting), were retrospectively analyzed. Subjects with a post baseline (post-BL) timepoint (TP) were analyzed for the incidence of ALC PD and an OTR designation of PRL, PD and other non-PD assessments (Stable Disease (SD), Non-PD and Unknown (UNK)). Results: We identified 1976 subjects with a total of 17134 post BL TPs. There were 1182 TPs (6%) with ALC PD. Out of these TPs with ALC PD, 497 TPs had OTR of PRL (42% TPs with ALC PD), 365 TPs (31%) were assessed as non-PD and 320 (27%) TPs were assessed as PD. 104 TPs (33%) of subjects with OTR of PD had at least one additional parameter driving PD. Thus, ALC PD is a common occurrence with BTKi and in line with the Cheson 2012 guidance, ALC PD alone should not be considered as overall progression. We propose that initial ALC PD with BTKi should not be considered a sign of progression but rather a treatment effect and should be assessed as PRL. However, PRL should only be assessed if Partial Response (PR) is achieved in at least 2 other involved iwCLL group A parameters (nodes, liver or spleen) and 1 group B parameter (hemoglobin or platelets). An initial decrease/normalization of the ALC compared to baseline with a subsequent progression compared to nadir, may be considered true progression in a setting of continued BTKi. If only one other group A parameter is involved and is PR with associated ALC PD, SD may be a more appropriate overall response than PRL. Conclusions: ALC PD and PRL are common in BTKi, but there is a need for standardization of the definition of ALC PD and its role in determination of OTR of PRL. We propose that ALC PD should be assessed by comparing ALC with nadir and not baseline. If PRL is assigned only when PR is met by other criteria along with ALC PD, PRL could be a part of determining Overall response rate (ORR) in protocols. Future prospective studies are needed to estimate the true incidence of ALC PD and its impact on ORR with BTKi as well as other agents which induce lymphocytosis.

Background: IWCLL 2008 and 2018 criteria require that all lymph nodes/nodal masses be ≤ 15mm in longest diameter (LDi) to be consistent with a CR. Lymph nodes or nodal masses >15mm in the LDi are considered abnormal. However, it has been observed that some bulky nodes may become thin and streak-like on follow-up timepoints (Figure 1) and may be normal by clinical and imaging standards (<10mm in short axis diameter) (Cheson et al Journal of Clinical Oncology, 17:1244, 1999) however, they continue to be >15mm in LDi (LDi Positive nodes- LDi+) and, hence, categorized as abnormal per iwCLL criteria. In lymphoma studies, FDG-PET negativity is the driver of CR, and residual disease on CT scan is allowed for CR. However, in the iwCLL response assessment, LDi+ nodes may prevent a true CR. Methods: 1168 patients across multiple phase III CLL clinical trials with targeted agents were analyzed, which were independently reviewed using iwCLL 2008 and 2018 criteria. To assess the impact of LDi+ nodes, we filtered our response to finding pts who had at least one lymph node with LDi >15mm (range 15.1 to 30mm) and, thus, a PR by imaging, but all other identified nodes either resolved or <10mm in short axis and the rest of the disease burden normalized. We also evaluated clinical information on all pts (e.g., bone marrow biopsy, complete blood count (CBC), Absolute Lymphocyte Count (ALC), and other confounding factors, when available). Figure 1: A large right axillary node at baseline (image on left), is reduced in size and is thin, streak like (image on right) but is abnormal as per iwCLL criteria by LDi definition. Results: Of 1168 pts, 161 (13.8%) had an overall response of PR because of these abnormal LDi+ nodes on imaging per iwCLL criteria, even though the rest of the disease burden had normalized and showed CR. Laboratory data (CBC and ALC) were available in all of these 161 patients and were normalized/CR. Bone marrow was available for 31 patients and was negative/CR in all of those patients in at least one follow-up assessment by both cellularity and CLL infiltration assessments (by either morphology, flow cytometry or immuno-histochemistry (IHC)). These pts continued to have a sustained response of CR for all other parameters for multiple follow up visits with a median follow up of about 6 months. Conclusion: Based on these data, approximately 13.8 % of pts with LDi+ nodes normal by clinical/imaging standards, clinical/laboratory parameters normalized and some with a normal bone marrow evaluation, but were labeled PR in overall assessment and denied a CR. These pts likely had achieved a CR as bone marrow is considered a gold standard for normalization of disease burden. These LDi+ lymph nodes by iwCLL criteria which are normal by clinical/imaging standards, likely represent scar tissue and not active disease based on normalization of the rest of the disease. These assessments made by stringent application of iwCLL criteria in assessing lymph nodes may result in underestimating the CR rate in a clinical trial. We propose an adaptation of the iwCLL criteria to allow hematologists/oncologists to update/override the radiology overall assessment from PR to CR if all other components for the oncology review (e.g., blood counts, bone marrow, target lesions, organ assessments) meet CR criteria, based on clinical judgment. This approach is being used universally in daily clinical practice (as well as by the site investigators) when assessing CLL patients and these abnormal LDi+ nodes by iwCLL criteria, do not prevent a CR. This proposed approach may help to reduce site-central discordance in a clinical trial setting. Further studies to correlate these findings with minimal residual disease in bone marrow/blood will help validate our findings. Figure 1 Disclosures Cheson: Trillium: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Jannsen: Consultancy; TG Therapeutics: Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Parexel: Consultancy; Kite: Consultancy; Symbio: Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees.

e16645 Background: Response Evaluation Criteria in Solid Tumors (RECIST) guidelines consider the measurement of treatment response based on tumor shrinkage due to the antitumor activity of cytotoxic drugs. However, tumor response can be misleading when molecular-targeted therapies or locoregional therapies are used in Hepatocellular carcinoma (HCC). RECIST 1.1 does not specify for changes in tumor vascularity or necrosis. The modified RECIST (mRECIST) adapts the concept of viable (Enhancing) tumor and tumoral necrosis in the assessment of response. According to mRECIST, if a tumor that is solid at baseline becomes entirely necrotic, all the tumors are evaluated as complete response (CR). Edeline et al. evaluated the response of sorafenib in HCC and reported that 26.2% of the patients who were classified as having stable disease (SD) according to RECIST were reclassified as responding to treatment, according to the mRECIST. Takada et al. analyzed tumor responses with sorafenib in HCC according to RECIST 1.1 and mRECIST where 13.1 % of patients were assessed as responders by mRECIST and 7.8 % by RECIST 1.1. There was a significant difference in overall survival (OS) between responders and non-responders according to mRECIST ( p = 0.0117), but no significant difference in OS between responders and non-responders according to RECIST 1.1 ( p = 0.0722). Methods: A retrospective review of time points associated with HCC was performed for 3 clinical trials with a total of 1060 patients with 3998 time points and evaluated using RECIST and mRECIST guidelines. The responses: overall response rate (ORR), CR and partial response (PR) were compared using both guidelines and correlated with disease progression. Results: At a subject level, there are 128 responders by RECIST, of which 73 progressed (57%), 274 responders by mRECIST, of which 156 progressed (57%); while of 148 responders by mRECIST, which were non-responders by RECIST only 80 progressed (54%) within the stipulated study duration. At the visit level, there are 520 timepoints of response by both RECIST & mRECIST, while there are 509 timepoints of response by mRECIST, which are SD by RECIST due to necrosis related difference in criteria implementation. Conclusions: It can be concluded that subjects with response by mRECIST with response or no response by RECIST tend to have an excellent correlation with progression as well. The use of mRECIST improves the outcome of the response in HCC treatment. [Table: see text]

4595 Background: mRECIST 2010 criteria for Hepatocellular Carcinoma (HCC) response assessment were focused on a concept of measuring viable tumor tissue showing enhancement in arterial phase of contrast enhanced CT/MRI, whereas RECIST 1.1 focuses mainly on the morphological measurements quantifying the tumor size irrespective of viability of the tumor and associated response to therapy. RECIST 1.1 does not address measures of antitumor activity other than tumor shrinkage, underestimating responses in HCC. Methods: We retrospectively analyzed multiple, phase III, multi-center clinical trials using both mRECIST and RECIST 1.1 criteria, read separately. The intent was to compare the overall responses at post-baseline assessments read independently by the two criteria. A total of 1682 subjects with 6159 post-baseline imaging timepoints were included in the analysis. The Overall response rate (ORR) as measured by sum of complete response (CR) and partial response(PR) and the Complete response rate (CRR) were evaluated. In addition, we also assessed the number of not evaluable (NE) time points by each criteria separately. We tested the following hypotheses 1. mRECIST may have better ORR and CRR compared to RECIST 1.1. 2. RECIST 1.1 may have more timepoints with Stable disease (SD) compared to mRECIST. 3. mRECIST may have more Not evaluable (NE) timepoints due to stringent imaging specifications. Results: The results are tabulated in the table below: Conclusions: The results above suggest that mRECIST shows more than double the CRR than RECIST 1.1, and the ORR is 62% higher using mRECIST than RECIST 1.1. Stable disease as expected was more commonly observed in RECIST 1.1 analysis. A NE response was 60% more common in mRECIST criteria evaluation. Our analysis confirms that reduction in viable tumor/enhancing area using contrast-enhanced radiologic imaging is the more optimal method to assess treatment response in HCC, and using RECIST 1.1 tumor measurement of a longest diameter as the sole measure of response, may not be adequate in response assessment for HCC. Our analysis validates and supports more widespread adoption of mRECIST in HCC tumor response assessment. Our results also indicate the need for uniform image acquisition and rigorous image quality control for a valid response in mRECIST criteria. [Table: see text]

e18058 Background: Metastasis is the leading cause of ovarian cancer (OC) related death with more than 70% of OC patients diagnosed with metastasis with five-year survival rates below 45%. OC cells mainly metastasize within the peritoneal cavity at presentation and throughout the course of the disease in 85% of the patients which involves exfoliation from the primary tumor, followed by survival and transport in the peritoneal fluid and finally metastatic colonization of the organs within the peritoneal cavity. There is a tendency of conventional imaging to underestimate the frequency of peritoneal spread. The purpose of the study was to obtain the frequency of organ involvement in OC metastasis and identify the most common route of OC metastasis. Methods: Retrospective study and analysis of two randomized double-blind trials was performed in patients with OC. Data was analyzed from these studies using blinded independent central review using RECIST 1.1 involving a total of 895 subjects, 528 and 367 respectively. A double read with adjudication by independent radiologists was performed for each scan based on the RECIST 1.1 criteria. Baseline tumor burden was assessed for all subjects using RECIST 1.1 criteria. At follow-up visits, data was specifically analyzed for New lesions. The readers had to select New lesion location from a pre-defined location list from a drop-down menu. Data was tabulated with frequency of subjects with New lesion per each location. Results: With both studies combined involving 895 subjects, total subjects with new metastasis observed in decreasing order for various organs were peritoneum/omentum (406), lymph nodes (315), ascites (207), liver (94), pleural effusion (65), pelvis (52) & lung (56). Other less common locations for new metastasis was abdominal wall, pleural deposits, spleen, brain, retroperitoneum and adrenal. We also looked at the possibility of disagreement between 2 readers in identifying such lesions leading to progression as below. Conclusions: It can be concluded that subjects with ovarian cancer tend to develop metastasis leading to progression per RECIST 1.1 in peritoneum / omentum, lymph nodes, liver and lung. Due to significant variability in identification of such discrete, ill-defined and/or small nature of lesions, targeted awareness and training should be incorporated to improve clinical outcome. [Table: see text]

Background:Mantle cell lymphoma (MCL) is a rare kind of Non-Hodgkin Lymphoma. The incidence of Gastrointestinal (GI) involvement is an important factor in assessing patients and determining the disease burden, although it has not been studied extensively. It is relatively difficult to detect GI involvement by endoscopy especially for the small bowel however more frequent use of Positron Emission Tomography- Computed Tomography (PET-CT) has improved detection rates. GI involvement has an important role in staging and overall assessment. With this background we hypothesized that the patients with GI involvement will have a poorer Overall Response Rate (ORR) and sustained response as compared to patients without GI involvement. Methods:A total of 120 patients were included in this retrospective analysis of multiple, phase II, clinical trials with MCL. These patients were independently reviewed using Lugano criteria. Patients with GI involvement at baseline and their subsequent response at Follow up were assessed. The Overall response rate (patients who achieved at least a CR or PR) and the sustained responses (of at least 6 months) of patients with GI involvement were compared with patients without GI involvement in this analysis. The subset of anatomical location of GI involvement was also assessed. Results: Out of a total of 120 patients, 34 had GI involvement noted on imaging. Correlative endoscopy findings were noted in 14 patients whereas in 20 patients endoscopy was not performed. The anatomical distribution of the gastrointestinal involvement on imaging was noted as follows: 17 Colon, 11 Small intestine (2 in Duodenum, 9 ileum), 11 Gastric, 1 Esophagus. Some patients had multifocal GI involvement. In patients with GI involvement (n=34), CR was noted in 13 patients (sustained response in 11) while PR was documented in 11 patients (sustained response in 5). In patients without the GI involvement (n=86) CR was noted in 39 patients (sustained response in 31) while PR was documented in 27 patients (sustained response in 16). Conclusion: Based on the results above it was observed that GI involvement was noted in approximately 28.3% of patients. Colon was the most common site involved, in 50% patients. Small Intestine and Gastric involvement were the next most common, 32% each. The incidence of GI involvement highlights the importance of predefining the imaging guidelines with the use of oral contrast to improve the detection of GI involvement. Any MCL patient with GI symptoms and suspected bowel involvement on imaging should always be followed up via endoscopy and biopsy when feasible to confirm the lymphomatous bowel involvement. The ORR in cases with GI involvement was 70.5% (24/34) and out of these only 47% (16/34) patients showed sustained response. Patients without GI involvement was 76.7% (66/86) and out of these only 54% (47/86) patients showed sustained response. Our analysis suggests that the GI involvement in MCL patients have slightly less ORR as well as sustained response. Further prospective studies with larger number of patients may be needed to substantiate this claim, if GI involvement has poorer prognosis. Disclosures No relevant conflicts of interest to declare.

e19015 Background: Revised Response Criteria in Malignant Lymphoma (Cheson 2007) and Lugano Classification are the most commonly used guidelines to assess response to treatment in lymphoma in clinical trials. While not drastically different from Cheson 2007, important clarifications and modifications were provided in Lugano Classification, specifically in the use of PET in response assessments. Methods: We retrospectively compared the blinded independent review of 25 subjects across multiple studies, assessed using Cheson 2007 and Lugano Classification on separate case report forms by the same reviewer per subject on 2 different dates. Focus was given on comparison of endpoint assessments of Progression-Free Survival (PFS), Duration of Complete Response (DOCR) and Duration of Response (DOR). Results: Assessments using Lugano Classification showed increased DOCR in 12% (3 out of 25), and DOR in 24% (6 out of 25) of the subjects. Cheson 2007 showed better DOR in 8% (2 out of 25) of the subjects. For PET positivity, Lugano Classification requires comparison with liver and mediastinal blood pool, whereas Cheson 2007 requires comparison to background or mediastinal blood pool. The results suggest that this difference in assessment of PET positivity (blood pool versus liver) leads to achieving Complete Response (CR) earlier, leading to longer DOCR and DOR when assessed using Lugano Classification compared to Cheson 2007. Lugano Classification also showed longer PFS in 16% (4 out of 25) of the subjects. When Progressive Disease (PD) was due to identification of new lesion(s), the two criteria showed similar PFS; however, when PD was due to lesion measurements and PET positivity assessment, Lugano Classification showed a longer PFS. Better PFS in Lugano Classification was observed because enlarging lymph nodes do not always show increased PET activity. Conclusions: In Independent review assessments for FDG avid lymphoma, using Lugano Classification showed better DOCR, DOR and PFS as compared to Cheson 2007. Further studies with increased number of subjects and intra-reader variability assessments are warranted to investigate the two criteria.

As per the International Myeloma Working Group (IMWG) 2016 criteria, response evaluation in multiple myeloma takes into consideration two main components: clinical data (e.g., SPEP, UPEP, Immunofixation, etc.) and imaging-based plasmacytoma/ myeloma-lesions assessment. Independent central review of imaging and clinical data may be required for clinical trial submission. Currently, no clear guidance is available on acceptable imaging modalities and various types of myeloma lesions seen on imaging. The purpose of this abstract is to describe in detail how to perform and incorporate imaging assessment in a clinical trial charter; this will facilitate the independent review process as well as address the most common questions related to imaging assessment. Historically, a skeletal survey/radiography has been the most commonly used imaging modality to assess disease burden at screening and inconsistently at post-treatment for response assessment in patients with multiple myeloma. However, skeletal survey often displays low sensitivity and resolution in identifying myeloma-lesions. With the more widespread availability of newer imaging techniques, there has been a shift in the image evaluation paradigm towards the modalities with superior resolution and sensitivity for early detection of myeloma progression, such as whole-body low dose CT, whole-body MRI and FDG-PET. The advantages and disadvantages of each modality need to be considered when designing the evaluation criteria for multiple myeloma clinical trials, tailored to suit the needs of the trial. This is especially important in the response assessment of patients who are receiving novel targeted therapeutic agents. For instance, with more modern myeloma treatments where a rapid objective response is typically achieved, assessing the metabolic activity of lesions on FDG-PET/CT can prove more valuable than using a skeletal survey. Documenting the changes in metabolic activity of the disease can be useful in the early evaluation of response or progression. Medullary and extramedullary myeloma-lesions/plasmacytomas show a varied appearance on different imaging modalities. Therefore, it is important to assess all myeloma-lesions consistently across various investigator sites involved in a clinical trial. We propose to assess soft tissue myeloma-lesions, including medullary and extramedullary plasmacytomas as measurable (target) lesions and pure lytic bony lesions as non-measurable (non-target) lesions. This approach allows for quantitative assessment of measurable lesions and qualitative assessment of the rest of the disease burden. A consistent imaging assessment by a Musculoskeletal Radiologist can then be integrated with clinical data by an Oncologist for IMWG response assessment. This can result in a guide for imaging-based independent review assessment in multiple myeloma clinical trials

e19061 Background: Positron Emission Tomography (PET) scans were applied to lymphoma as early as in 1990s. Revised criteria for lymphoma assessment was published in 2007 by International Working Group (IWG). The criteria for PET into response assessment were added due to better sensitivity and superiority of PET over CT and its ability to distinguish between viable tumor and necrosis or fibrosis in residual mass after treatment. PET was primarily recommended for patients with FDG avid curable lymphomas such as Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) and later for the post-treatment assessment of DLBCL and HL. The Lugano Classification 2014 regarded FDG PET/CT to be the standard for staging and assessment of all FDG-avid histologies. Methods: A retrospective review of 10 Lymphoma studies with a total of 1,537 subjects and 17,394 time points was carried out using PET in addition to CT as per imaging schedule. There were 5 clinical trials with a total of 1,169 subjects with 15,480 time points using IWG-NHL classification 2007 while 5 clinical trials with a total of 729 subjects and 1,914 time points using Lugano classification 2014. The number of subjects and time points with PET where PET had an impact on the overall assessment was calculated. Results: PET was available for a total of 1,159 subjects (out of 1,537) and 4,688 time points (out of 17,394) across all 10 studies. Out of 4,688 visits with PET, 956 (20.4%) visits had an impact on overall assessment due to additional metabolic findings. Out of 1,159 subjects with PET, 462 (39.9%) subjects had an impact on overall assessment and study endpoints due to additional uptake related findings. The impact across different studies was between 7% to 59% possibly due to difference in indication, line of therapy and blinded independent review design. The most common impact due to PET was related to complete response and disease progression. Conclusions: It can be concluded that PET significantly impacts assessments and imaging endpoints for lymphoma clinical trials using IWG-NHL classification or Lugano classification. Thus, addition of PET improves the outcome of the response not only in lymphoma treatment and diagnosis, but also clinical trial outcomes. [Table: see text]

Background: The Lugano classification criteria introduced in 2014 is widely used in clinical trials as well as in clinical practice for response assessment in Lymphoma. The criteria recommend a combination of disease morphology assessment using Computed Tomography (CT) and lesion metabolic activity assessment on Positron Emission Tomography (PET), with PET metabolic assessments being the driver for overall response assessment. In this study, we analyzed the alignment between assessments made using both modalities. The independent review assessments of 583 subjects with 1032 follow up timepoints from multiple Phase I to Phase-III multi-center clinical trials to determine the alignment between assessments made using both modalities. Methods: 583 subjects with 1032 post-baseline timepoints from multiple phases I to phase-III multi-center clinical trials on lymphoma were retrospectively analyzed using the independent review data. All clinical trials used the Lugano Classification as a response assessment criteria. The variability between the PET-based metabolic assessments [Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), No Metabolic Response (NMR) and Progressive Metabolic Disease (PMD)] and CT-based morphological assessments [(Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)] for the same timepoint was analyzed by comparing the following: Timepoints where PET-based assessment was CMR, but CT based assessment was not CR and vice versa Timepoints where PET-based assessment was PMD, but CT based assessment was not PD and vice versa Results: 280 timepoints had CMR on PET, but only 109 of these 280 timepoints (39%) had an assessment of CR on CT (147 were PR, 23 SD, and 1 PD) 138 timepoints that had CR on CT but 32 (23%) were non-CMR on PET (29 were PMR, 1 NMR, and 2 PMD). 343 timepoints had PMD on PET and 301 of these 343 timepoints (88%) had an assessment of PD on CT (2 were CR, 28 PR, 12 SD) 115 timepoints had PD on CT Scan, but 10 (8%) timepoints that had PD on CT were non-PMD on PET (1 CMR, 6 PMR, and 3 NMR) Conclusion: The results shown above suggest that PET and CT based assessments may not always be aligned. CMR on PET can be associated with residual disease on CT in about 61%, whereas a CR on CT may have associated residual metabolic activity on PET in 23% cases. This is in alignment with the Lugano criteria where PET-based metabolic activity assessment is considered a driver in lymphoma response assessment than CT. PET findings show the metabolic activity of the lesions, whereas morphological response on CT scan may be affected by underlying treatment-related effects such as fibrosis and may not always align with PET response. A PMD on PET is associated with a progression on CT scan most of the times and vice versa, but in a small number of the case, progression may not be aligned on two modalities and may need further investigation by biopsy and follow-up imaging. Disclosures No relevant conflicts of interest to declare.

PURPOSETo evaluate the effects of preoperative embolization on overall surgical outcomes after meningioma resection and determine whether pre- and postembolization tumor enhancement patterns on magnetic resonance imaging (MRI) scans can be used to assess the efficacy of embolization.METHODSWe developed a prospective database of all patients who underwent surgical resection with or without preoperative embolization for extra-axial intracranial meningiomas from 2004 to 2010. Using specialized computer software, the total volume of enhancement was calculated in pre- and postembolization MRI scans to quantify the percentage of embolization, which was described as the embolization fraction (EF).RESULTSA total of 89 patients underwent surgical resection. Fifty two patients underwent embolization prior to surgery. Tumor location significantly correlated with the decision to embolize preoperatively. Adequate embolization was achieved in 58% of patients. Forty four patients (84.6%) had a postsurgical Karnofsky performance score (KPS) of 80 or above, while 46 patients (88.4%) had a postsurgical Glascow Outcome Score (GOS) of 4 or 5. The mean EF was 25.03% with a median of 18.72%. A greater extent of embolization as quantified by EF led to decreased intraoperative blood loss (r = -.319, P = .022) and better postsurgical outcomes as defined by KPS (r = .279, P = .044).CONCLUSIONSPre- and postembolization tumor enhancement patterns on magnetic resonance imaging defined as EF correlate with improved surgical facilitation and postoperative functional outcomes in the management of intracranial meningioma.