PET-CT In Assessment Research Articles

Utility of PET-CT for assessment of response to neo-adjuvant chemotherapy in breast cancer.

12 Background: Response to neo-adjuvant chemotherapy (NACT) is associated with prognosis in non-metastatic breast cancer and can potentially inform further therapeutic options. The aim of this study was to correlate post NACT response on PET CT with pathological response. Methods: All patients who underwent pre- NACT (baseline) and post NACT PET CT imaging with F-18 FDG in a dose of 5-7 MBq/kg body weight with a minimum of 185 MBq given intravenously were retrospectively analyzed. Scan was performed on GE Discovery 710 whole-body PET scan with 128 slice CT. Relevant clinical and imaging related details were extracted from the treatment records. Post NACT PET response (PERCIST criteria) in the primary tumor and nodes was correlated with the pathological response on the post surgical specimen. Analysis was done using Microsoft Excel and SPSS v20 (IBM SPSS). Results: The median age was 49 years (range 30-76 years). 83.1% of patients had node positive disease on baseline PET imaging (not pathologically confirmed). Post chemotherapy PET showed complete metabolic response in the primary tumor and regional nodes in 56.3% and 74% of patients respectively. Two patients had progressive local disease. Pathological complete response rates post surgery in triple negative, Her2 neu positive and ER positive group was 50%, 34% and 12% respectively. The sensitivity, specificity, positive predictive value and negative predictive value is tabulated below. Conclusions: Overall FDG PET CT showed good specificity with limited sensitivity for post NACT response assessment in breast cancer. Our results suggest that post NACT PET CT may have limited utility for clinical decision making and at present its use cannot be recommended outside of a clinical trial.[Table: see text]

Multicenter, randomized phase II study of epcoritamab for patients with large B-cell lymphomas achieving a partial response after CD19-directed CAR T-cell therapy (CAR-T).

TPS7100 Background: Despite the promising efficacy of CAR-T for patients with relapsed or refractory (R/R) large B-cell lymphomas (LBCL), more than 60% of patients will relapse, the majority of which occur in the first 6 months. Approximately 30% of patients with LBCL treated with CAR-T achieve a partial response (PR) on day 30 (D30) PET-CT assessment. Of patients in a D30 PR, 70% will eventually progress, yet the standard of care remains close observation. Early consolidative treatment strategies utilizing therapies with a different mechanism of action may improve outcomes, but there are currently no reliable biomarkers. Epcoritamab (Epco), a bispecific antibody directed against CD20 and CD3, has been approved by the FDA for LBCL patients who relapse after at least 2 lines of therapy. In the phase 2 study, Epco was associated with an overall response rate (ORR) of 63% and a complete response (CR) rate of 39%, including similar responses in a subset of patients who were relapsed 100 days post CAR-T. This study is a trial-in-progress that will evaluate the efficacy of epco compared to observation for patients with LBCLs achieving a PR on D30 post CAR-T PET-CT assessment. Methods: This is an investigator-initiated, randomized, phase II, multicenter, open-label study (NCT06238648) evaluating epco monotherapy for a fixed duration of 12 cycles compared to observation for LBCL patients with D30 PR after standard of care CAR-T. A maximum of 120 patients will be randomized 1:1 to epco or observation across 10 academic centers. Stratification factors include line of CAR-T (second vs third line) and costimulatory domain (CD28 vs 4-1BB). Key inclusion criteria include PET evidence of a D30 PR. non-bulky disease ( <7.5cm), ANC of >1000, hemoglobin >7 g/dL if asymptomatic or >8 if symptomatic, platelet count >50,000. G-CSF, pRBCs and platelet transfusions are allowed. Key exclusion criteria include prior anti CD20xCD3 bispecific antibody therapy, ongoing or uncontrolled CRS or ICANS, and active or symptomatic CNS disease. Epco is administered subcutaneously at a dose of 0.16mg on day 1, 0.8mg on day 8, prior to full dose of 48mg on day 15. Epco is administered weekly in 28 day cycles (C) for C1-3, on day 1 and 15 of C4-9 and on day 1 of C10-12. PET-CT response is assessed by the 2014 Lugano criteria after 2 cycles, and then every 3 months during active treatment. The primary objective is efficacy, measured as conversion from D30 PR to CR. The secondary endpoints include frequency and severity of treatment emergent adverse events, ORR, duration of response, duration of complete response, progression free survival, event free survival, and overall survival. Peripheral blood samples will be collected pre-treatment and during treatment to assess for biomarkers of response and resistance. The study was activated in January 2024 and recruitment is ongoing. Clinical trial information: NCT06238648 .

Prediction of Patient Outcomes in Locally Advanced Cervical Carcinoma Following Chemoradiotherapy-Comparative Effectiveness of Magnetic Resonance Imaging and 2-Deoxy-2-[18F]fluoro-D-glucose Imaging.

To evaluate the utility and comparative effectiveness of three five-point qualitative scoring systems for assessing response on PET-CT and MRI imaging individually and in combination, following curative-intent chemoradiotherapy (CRT) in locally advanced cervical cancer (LACC). Their performance in the prediction of subsequent patient outcomes was also assessed; Methods: Ninety-seven patients with histologically confirmed LACC treated with CRT using standard institutional protocols at a single centre who underwent PET-CT and MRI at staging and post treatment were identified retrospectively from an institutional database. The post-CRT imaging studies were independently reviewed, and response assessed using five-point scoring tools for T2WI, DWI, and FDG PET-CT. Patient characteristics, staging, treatment, and follow-up details including progression-free survival (PFS) and overall survival (OS) outcomes were collected. To compare diagnostic performance metrics, a two-proportion z-test was employed. A Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. The T2WI (p < 0.00001, p < 0.00001) and DWI response scores (p < 0.00001, p = 0.0002) had higher specificity and accuracy than the PET-CT. The T2WI score had the highest positive predictive value (PPV), while the negative predictive value (NPV) was consistent across modalities. The combined MR scores maintained high NPV, PPV, specificity, and sensitivity, and the PET/MR consensus scores showed superior diagnostic accuracy and specificity compared to the PET-CT score alone (p = 0.02926, p = 0.0083). The Kaplan-Meier analysis revealed significant differences in the PFS based on the T2WI (p < 0.001), DWI (p < 0.001), combined MR (p = 0.003), and PET-CT/MR consensus scores (p < 0.001) and in the OS for the T2WI (p < 0.001), DWI (p < 0.001), and combined MR scores (p = 0.031) between responders and non-responders. Post-CRT response assessment using qualitative MR scoring and/or consensus PET-CT and MRI scoring was a better predictor of outcome compared to PET-CT assessment alone. This requires validation in a larger prospective study but offers the potential to help stratify patient follow-up in the future.

PD-0399 Timing of Response Assessment PET CT in OPSCC Post Treatment and Salvage Neck Dissection Rates

PD-0399 Timing of Response Assessment PET CT in OPSCC Post Treatment and Salvage Neck Dissection Rates

HL-300 Efficacy of Brentuximab Vedotin Plus Conventional Chemotherapy Regimens as Pre–Autologous Stem Cell Transplantation Re-Induction Salvage Therapy in Relapsed/Refractory Classical Hodgkin Lymphoma

Adding brentuximab vedotin (BV) to traditional chemotherapy protocols, followed by autologous stem cell transplantation (ASCT), has effected fundamental change in the treatment approach of relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). Several studies have shown a superior rate of complete remission (CR) up to 70%-87% in patients receiving BV-based salvage chemotherapy. Previous studies exposed pre-ASCT PET-CT negativity as the most important factor affecting the post-transplant outcome. Therefore, our objective was to evaluate the efficacy of BV-chemotherapy regimens by PET CT assessment of response rate. Single-center, descriptive retrospective analysis of 20 patients with R/R cHL, eligible for ASCT, treated at the University Clinic for Hematology - Skopje between January 2017 and January 2022. We reviewed demographic and clinical characteristics pointing to disease stage and the presence of unfavorable prognostic factors, treatment, and outcome. Patients received BV-chemotherapy combinations, including BV-DHAP and BV-ICE, or PET-adapted sequential chemotherapy with BV followed by augmented ICE. In patients receiving a BV combination, PET-CT was performed after 3 cycles. In patients treated with sequential chemotherapy who did not achieve response by 3 cycles of BV and received augmented ICE, PET-CT was performed after the second cycle. Fourteen patients (70%) had refractory disease and 6 patients (30%) had relapsed disease (3 with early relapse). The majority were male (70%). The mean age at the time of assessment was 39 (range: 15-63). According to the EORTC staging system, 14 patients (70%) were initially defined to have advanced stage. Patients had received 1-3 previous treatment lines. Seven patients with refractory disease received BV-DHAP. After 3 cycles, PET negativity was achieved in 4 patients (57.1%) and these patients proceeded to ASCT. All 5 patients with relapsed disease treated with BV-DHAP achieved CR. Two patients with refractory disease received BV-ICE and both of them progressed. Among 5 patients with refractory disease receiving sequential therapy, CR was confirmed in 3 (60%). One patient with early relapse received BV-augmented ICE and achieved CR. BV-based salvage chemotherapy is an effective treatment strategy for patients with R/R cHL, and it is reasonable to be moved forward as standard second-line therapy in R/R CD30+ cHL.

Prognostic evaluation value of (18)F-FDG PET-CT in Hodgkin's lymphoma after treatment

Objective: To investigate the prognostic value of (18)F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ((18)F-FDG-PET-CT) in Hodgkin's lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV(max)) of lesion and liver SUV (rLL), SUV(max) reduction between baseline PET (PET-0) and PET-end (ΔSUV(max)), and Deauville 5-point scale (5-PS). Methods: Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV(max) were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results: There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference (P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference (P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS (r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95%CI: 0.825-1.000) and 0.91 (95%CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods (P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients (P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL (P<0.05). Conclusions: The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

PET-CT for Assessment of Multiple Myeloma Disease Burden and Metabolic Response before and after Carfilzomib-Based Induction, Consolidation and Carfilzomib Maintenance Therapy: Data from the UK NCRI Cardamon Study

PET-CT for Assessment of Multiple Myeloma Disease Burden and Metabolic Response before and after Carfilzomib-Based Induction, Consolidation and Carfilzomib Maintenance Therapy: Data from the UK NCRI Cardamon Study

P-015: Is it time to revisit role of PET-CT imaging and its integration with other parameters in International Myeloma Working Group (IMWG) response assessment criteria?

<h3>Background</h3> 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.

Interim-PET As a Predictive Factor in Patients with Hodgkin's Lymphoma

Introduction. PET-CT is the new standard for staging of patients with Hodgkin Lymphoma (HL). However, it is becoming obvious that the role of PET-CT in assessment of response is not limited to imaging at the end-of-treatment. In recent years the prognostic role of interim PET-CT and attempt to use PET response-adapted therapy has come under evaluation across a number of international studies with promising results. Here we report the results of a multicenter retrospective study of interim PET in HL.Methods. 53 patients with HL with a stage I-II (64%), III-IV (36%) who were admitted between August 2012 and May 2017 to 10 Ukrainian hematological centers were included in this retrospective analysis. Metabolic PET-CT imaging was performed at participating PET centers according to routine protocols, compatible with EANM guidelines for FDG PET-CT imaging in malignant tumors. Interim PET (PET2) was performed at 15.5 ±3 days (range, 5-26) after 2d and 4th cycles of traetment in 75% and 25% cases, respectively. Patients were treated with ABVD or BEACOPP-14/esc based on risk group. The primary endpoint was event-free survival (EFS), defined as disease progression or death from HL.Results. Median age of patients at diagnosis was 32 years (range 17-56), and 63% of patients were female. B symptoms were present in 42% (22/53), extranodal disease in 4% (2/53), and bulky disease (>10 cm in any dimension) in 25% (13/53) of pts. Median follow-up was 24 months from diagnosis. Interim PET-CT, performed after chemotherapy, was categorized as Deauville 1-2 in 34 patients (56%), Deauville 3 in 12 (32%), Deauville 4 in 5 (10%), and Deauville 5 in 2 (2%). The threshold of positivity was set for a residual uptake higher than the liver background (grade 4 and 5 of the scale).13% (7/53) and 87% (46/53) patients in our cohort were PET2-positive (PET2+) and negative (PET2-), respectively (p<0.05). In total, disease progression was documented in 43% (3/7) of PET2+ patients and 11% (5/46) if PET2-negative patients (p<0.05). There was 1 death from refractory disease. 3-year EFS for patients with PET2+ vs PET2- was 45% vs 77%, respectively (p<0.05).Also, we compared EFS in patients with PET2 according to the Deauville score subgroups: 1-2 vs 3 vs 4-5 scores. The 3-year EFS was significant difference: 91% for the Deauville 1-2 subgroup versus 86% for Deauville 3 versus 46% for Deauville 4-5, (p < 0.004).Conclusion. Interim PET-CT is an important tool for clinicians in the diagnosis and management of patients with HL. The pronostic role and validity of the Deauville 5PS for interpretation of interim PET should be confirmed prospectively. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Maintenance Treatment with Lenalidomide for Multiple Myeloma Increases the Proportion of MRD Negative (Flow-/PET-CT-) Patients

IntroductionLenalidomide maintenance therapy in Multiple Myeloma has been used in order to prolong the Progression-Free Survival (PFS) obtained with any induction therapy through the depletion of residual tumor burden. In this way, it is well established the value of Minimal Residual Disease (MRD) assessed by flow cytometry (FCM) as an independent prognosis factor in Multiple Myeloma. Similarly, patients who become PET-CT negative (when previously they have proved lesions) have better survival outcomes; in fact, this has recently been accepted as a new response criterion.However, the available data about the complementary use of both techniques in terms of prognosis are limited. The aim of this study is to analyze the prognostic impact of achieving negative residual disease by FCM and PET-CT during Lenalidomide maintenance therapy.MethodsWe retrospectively selected 87 Multiple Myeloma patients from 3 Spanish hospitals (Hospital 12 de Octubre, Hospital Virgen de las Nieves and Hospital Ramón y Cajal). Main selection criterion was to start Lenalidomide maintenance therapy between 2008-2017; the previous induction therapy was heterogeneous. 75% of included patients had previously received an autologous stem cell transplant. We collected data about baseline variables, clinical and biological parameters, therapy administered and FCM and PET-CT assessment at diagnosis, post-induction and during maintenance. Statistical analysis was realized with SPSS 21.0 version (SPSS, Inc., Armonk, NY).ResultsResponse at the beginning of maintenance was VGPR or CR in 78% of patients and 48,3% were MRD-. Initial PET-CT was positive in 31%. After a median of 21 Lenalidomide cycles, 32% of patients with initial MRD+ achieve MRD-; meanwhile, 48,1% of patients with initial PET-CT+ become negative.When we jointly assessed FCM and PET-CT results during maintenance therapy (49 patients had been studied by both techniques), we detected a significant difference in terms of PFS between patients that achieve combined PET-/FCM- and the other groups (median PFS not reached vs 32 months, respectively; p<0,0001) (Fig.1). We also found a trend to longer OS in patients PET-/FCM- (4-year OS 100% vs 83%; p=0,053). Patients with standard-risk cytogenetics were more frequently PET-/FCM- than in the high-risk cytogenetics group (31,8% vs 5,6%; p=0,002); nevertheless high-risk cytogenetics patients that achieve PET-/FCM- (n=3) also had prolonged PFS (4-year PFS 100%).ConclusionLenalidomide maintenance therapy increases the proportion of patients that achieve combined PET-/FCM-. Both techniques are complementary and their combination allows us to identify a subset of PET-/FCM- patients with very good prognosis and PFS outcomes significantly superior than the other patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

18f-FDG PET-CT Assessment of Responses to Salvage Therapy and Autologous Stem Cell Transplant (ASCT) in Relapsed/Refractory Classical Hodgkin Lymphoma (cHL)

Background:Approximately 25% of patients with cHL have relapsed or refractory (r/r) disease. Although salvage chemo-radiotherapy followed by autologous stem cell transplant (ASCT) offers the best chance of freedom from treatment failure (FFTF) (~50%), a portion patients have a poor prognosis despite this approach. Traditional prognostic scores are less well validated than in de novo disease, and hence 18F-FDG PET-CT, the gold-standard imaging modality in cHL, has an increasing role as a powerful prognostic indicator in this context.Our aims were a) to compare response rates to salvage therapy using 18F-FDG PET-CT (reported according to Lugano 2014 criteria) with trial-reported outcomes; and b) to assess the prognostic value of 18F-FDG PET-CT in this context.Method:Retrospective data were collected on r/r cHL patients treated across 3 UK hospital sites (2011-2017). PET-CT scans were retrospectively reviewed according to Lugano 2014 response criteria i.e. complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR) and progressive metabolic disease (PMD). Prognostic scores were calculated as described by Jostings et al. 2000.Results:34 patients were identified: 21 with refractory cHL (<90 days) and 13 with relapsed disease. Median age was 43 years (range 14-77). Median time to relapse was 94 weeks (193-687). 100% patients had a prognostic score of <2, with 90% <1 (score unable to be calculated: n=2). 88% patients achieved an overall response (ORR) after 1st line salvage therapy, with 33% achieving CMR and 55% PMR (18F-FDG PET not performed: n=1). Patients were treated with 1-4 lines of salvage therapy (median= 1), with 33% receiving brentuximab vedotin. Of the 82% patients that proceeded to ASCT, 46% were in CMR, 50% were in PMR and 4% had mixed disease response. 47% of patients achieved CMR post-ASCT, with FFTF in 37% (Post-ASCT 18F-FDG PET unavailable: n=3). As shown in the table below, there was a 55% rate of FFTF in patients with CMR post 1st line salvage therapy, compared with a 23% rate of FFTF in patients with PMR post 1st line salvage. 38% of patients with an overall CMR pre-ASCT had FFTF, compared with 43% with overall PMR.Conclusion:There is a wide discrepancy in FFTF, comparable with previous trial data, between patients achieving CMR and those achieving a PMR on 18F-FDG PET-CT post 1st line salvage chemotherapy. However, patients who received multiple lines of salvage therapy achieved similar rates of FF2F, irrespective of their metabolic response on their pre-ASCT 18F-FDG PET-CT. This suggests that 18F-FDG PET-CT may have limited prognostic value in this setting. [Display omitted] DisclosuresHildyard:ADC Therapeutics: Research Funding. Collins:Pfizer: Consultancy, Honoraria; ADC Therapeutics: Research Funding; MSD: Consultancy, Honoraria; Celleron: Consultancy; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Amgen: Research Funding.

Phase II trial of GVDexa (gemcitabine, vinorelbine and dexamethasone) regimen in relapsed/refractory Hodgkin’s lymphoma.

e19519 Background: Gemcitabine, vinorelbine and liposomal doxorubicin (GVD) is an effective regimen in relapsed/refractory Hodgkin’s lymphoma (RRHL). Conventional second-line chemotherapy is still required as the cost of immunotherapy and antibody-drug conjugates are prohibitive to Indian patients. We report the results of a phase II, open-label, single-arm, single centre interventional study in RRHL where dexamethasone replaced liposomal doxorubicin. Methods: Adult patients (≥18 years) with RRHL at first or second relapse were included. GVDex was delivered as outpatient once in 3 weeks (Gemcitabine 1000 mg/m2 IV over 30 min on D1,8; Vinblastine 25 mg/m2 IV fast infusion on D1,8; Dexamethasone 40 mg PO D1-4) for two cycles followed by interim PET CT assessment by Cheson’s criteria and Deauville scoring. The primary endpoint was the objective response rate (ORR = complete response + partial response). The sample size was calculated using Fleming’s 2-stage model (α error: 0.05 and power: 0.8). Twenty patients were required in the first stage. If there were ≥16 responses, the null hypothesis would be rejected and the study stopped. Results: Between May 2016, and December 2020, 26 patients with RRHL were screened, and 20 were enrolled: primary resistant HL-8 patients (40%) and relapsed HL- 12 patients (60%). The median age was 35 years (range:20-52). Six patients (30%) presented with limited stage and 14 patients (70%) with advanced stage HL at relapse. GVdex was delivered as a first salvage regimen in 18 patients (90%) and second in 2 patients. After 2 cycles of GVDex, 16 (80%) had responded [partial response: 12 (60%); complete response: 4 (20%)]. Median number of cycles of GVDex: 3 (range: 1-4). Five patients (25%) required dose reductions due to chemotherapy-related toxicities. The median duration of objective response was 13.4 months. Eleven patients (55%) underwent high-dose chemotherapy supported by autologous stem cell rescue. After a median follow-up of 25 months (95% CI: 5.9-44.5), the median progression-free survival (PFS) was 24.7 months, and the median overall survival (OS) has not been reached. The estimated 2-year PFS was 44%, and the 2-year OS was 79%. The most common treatment-related adverse events were anemia (100%), neutropenia (70%, 14/20) and fatigue (70%, 14/20). Grade 3 or 4 treatment-related AEs occurred in 14 patients (70%). Grade ≥3 neutropenia occurred in 9 patients (45%) and febrile neutropenia in 3 patients (15%). Serious adverse events were reported in 3 patients (15%). One patient developed Ficat and Arlet classification stage III avascular necrosis of the femoral head. One patient died due to suspected COVID-19 pneumonia (non-neutropenic fever) before cycle 2 of chemotherapy. Conclusions: GVDex it is an effective salvage regimen with acceptable toxicity in patients with RRHL. Clinical trial information: CTRI/2017/04/008361.

Effects of two patient-specific dosing protocols on measurement of myocardial blood flow with 3D 82Rb cardiac PET

Clinical measurement of myocardial blood flow (MBF) has emerged as an important component of routine PET-CT assessment of myocardial perfusion in patients with known or suspected coronary artery disease. Although multiple society guidelines recommend patient-specific dosing, there is a lack of studies evaluating the efficacy of patient-specific dosing for quantitative MBF accuracy. Two patient-specific dosing protocols (weight- and BMI-adjusted) were retrospectively evaluated in 435 consecutive clinical patients referred for PET myocardial perfusion assessment. MBF was estimated at rest and after regadenoson-induced hyperemia. The effect of dosing protocol on dose reduction, PET scanner saturation, relative perfusion, and image quality was compared. The effect of PET saturation on the accuracy of MBF and myocardial flow reserve (MFR) in remote myocardium was assessed with multivariable linear regression. BMI-adjusted dosing was associated with lower administered 82Rb activities (1036.0 ± 274 vs. 1147 ± 274MBq, p = 0.003) and lower PET scanner saturation incidence (28 vs. 38%, p = 0.006) and severity (median saturation severity index 0.219 ± 0.33 vs. 0.397 ± 0.59%, p = 0.018) compared to weight-adjusted dosing. PET saturation that occurred with either dosing protocol was moderate and resulted in modest remote MBF and MFR biases ranging from 2 to 9% after adjusting for patient age, sex, BMI, rate-pressure product, and LV ejection fraction. No adverse effects of BMI dose adjustment were observed in relative perfusion assessment or image quality. Patient-specific dosing according to BMI is an effective method for guideline-directed dose reduction while maintaining image quality and accuracy for routine MBF and MFR quantification.

Response rate and diagnostic accuracy of early PET-CT during neo-adjuvant therapies in oesophageal adenocarcinoma: A systematic review and meta-analysis.

Only 25% of oesophageal adenocarcinoma (OAC) patients have a pathological response to neo-adjuvant therapy (NAT) before oesophagectomy. Early response assessment using PET imaging may help guide management of these patients. We performed a systematic review and meta-analysis to synthesise the evidence detailing response rate and diagnostic accuracy of early PET-CT assessment. We systematically searched several databases including MEDLINE and Embase. Studies with mixed cohorts of histology, tumour location and a repeat PET-CT assessment after more than one cycle of NAT were excluded. Reference standard was pathological response defined by Becker or Mandard classifications. Primary outcome was metabolic response rate after one cycle of NAT defined by a reduction in maximum standardised uptake value (SUVmax) of 35%. Secondary outcome was diagnostic accuracy of treatment response prediction, defined as the sensitivity and specificity of early PET-CT using this threshold. Quality of evidence was also assessed. Random-effects meta-analysis pooled response rates and diagnostic accuracy. This study was registered with PROSPERO (CRD42019147034). Overall, 1341 articles were screened, and 6 studies were eligible for analysis. These studies reported data for 518 patients (aged 27-78years; 452 [87.3%] were men) between 2005 and 2020. Pooled sensitivity of early metabolic response to predict pathological response was 77.2% (95% CI 53.2%-100%). Significant heterogeneity existed between studies (I2 =80.6% (95% CI 38.9%-93.8%), P=.006). Pooled specificity was 75.0% (95% CI 68.2%-82.5%), however, no significant heterogeneity between studies existed (I2 =0.0% (95% CI 0.0%-67.4%), P=.73). High-quality evidence is lacking, and few studies met the inclusion criteria of this systematic review. The sensitivity of PET using a SUVmax reduction threshold of 35% was suboptimal and varied widely. However, specificity was consistent across studies with a pooled value of 75.0%, suggesting early PET assessment is a better predictor of treatment resistance thanof pathologicalresponse. Further research is required to define optimal PET-guided treatment decisions in OAC.

Incremental value of endoscopic brush cytology in response assessment after chemo-irradiation for Esophageal cancer.

Response assessment after chemo-radiotherapy (CTRT) in locally advanced esophageal cancer is usually performed using a PET-CT scan, an upper GI endoscopy (UGIE) and histological correlation with biopsy or cytology. We aim to study the incremental value of brush cytology in addition to PET-CT for response assessment. In this retrospective analysis, 40 patients with Stage II- IV carcinoma esophagus treated with radical intent between June 2015 and August 2019 were included. Patients were treated with either upfront concurrent CTRT or neo-adjuvant chemotherapy followed by CTRT. All patients underwent PET-CT and UGIE for initial staging and response assessment on follow-up. Patients with esophageal stricture (disease related or treatment induced) had brush cytology done during UGIE. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of brush cytology were calculated considering serial clinical follow-up as gold standard. Twenty-three male (57.5%) and 17 (42.5%) female patients with median age of 57years (range: 27 - 79years) were analyzed. Concurrent CTRT was delivered in 52.5%; 75% patients were treated with intensity-modulated radiotherapy (IMRT); median RT dose was 63Gy (range- 41.4 to 64Gy). At a median follow-up of 16months (range 6- 54months), 20 patients (55.5%) were clinically controlled, 9 (25%) had local recurrence, 5 (13.8%) had loco-regional recurrence and 2 had distant metastasis. Considering clinical follow-up as the gold standard, sensitivity, PPV and NPV of PET-CT combined with brush cytology improved compared to PET-CT alone and was found to be 75%, 90%, 85.7% and 81.8% respectively. We found that brush cytology on endoscopy is a simple tool with high specificity which adds value to the findings of response assessment PET-CT scan and thereby can increase the confidence of the treating oncologist in making clinical decisions.

Phase I/II Dose-Escalation Study of Lenalidomide in Combination with R-GDP for Treatment of Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Followed By Maintenance Lenalidomide

Introduction Patients with relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL) whom are transplant-ineligible have limited treatment options. To address this specific treatment challenge, we undertook a clinical trial combining lenalidomide and rituximab (R2) with an established salvage regimen for DLBCL in gemcitabine, dexamethasone, cisplatin (GDP). Methods This was a single-center, open-label, phase I/II dose-escalation study of lenalidomide in combination with R-GDP for treatment of transplant-ineligible R/R DLBCL. The study was divided into a phase I dose-escalation study employing a '3+3' design followed by an expansion (phase II) portion with the recommended phase 2 dosing (RP2D), and a maintenance phase using 10 mg daily for 21 out of a 28-day cycle, for up to 1 year. The primary objective was to determine the maximum tolerated dose (MTD) of lenalidomide when combined with RGDP while secondary objectives was to analyze progression-free (PFS) and overall (OS) survival. Dose-escalation included 4 dose levels (DL) of 10 mg, 15 mg, 20 mg, 25 mg, starting at DL1. Lenalidomide was given for 6 cycles during induction therapy on days 1-21 every 28 days for a total of 6 cycles. The expansion phase used lenalidomide at the RP2D. Based on interim PET-CT assessment after cycle 2 (PET-2), patients in CR completed 2 more cycles of R2-GDP followed by two cycles of R2 and then stopped treatment without lenalidomide maintenance; patients with stable disease (SD) or partial remission (PR) completed 2 more cycles of R2-GDP and repeated PET-CT assessment after cycle 4 (PET-4). Based on PET-4, all responding patients (CR or PR) completed a further 2 cycles followed by maintenance with lenalidomide 10mg/day. Patients who failed to achieve at least PR at the point of PET-4 assessment were deemed treatment failure and stopped study treatment. Results The first patient was enrolled in February 2017. At data cut-off (July 20, 2020), 10 patients were enrolled into the dose-escalation study and a further 9 patients in the phase II part using lenalidomide at the RP2D of 15 mg/day (DL2). The MTD of lenalidomide of 15 mg/day was established after 2 of 3 patients at 20 mg/day (DL3) suffered neutropenic sepsis. The median age was 57.5 years (range, 40-76). Seven patients had primary refractory disease after R-CHOP while 13 had relapsed disease. Median time from first diagnosis to trial enrolment was 11.87 months. Median number of prior treatments were 2, including 4 patients who had previously undergone autologous transplant. After a median follow-up of 23.6 months in surviving patients, overall response rate was 68% (CR, N=7; PR, N=6). Median number of lenalidomide cycles completed in the induction phase was 4. Four patients completed less than 3 lenalidomide cycles due to progressive disease (PD). Nine patients died while on follow-up, 7 from PD and 2 infective deaths related to study treatment. The most common grade 3/4 treatment-emergent adverse events were neutropenia and thrombocytopenia with 4 and 11 patients experiencing at least one episode of grade 3 and 4 neutropenia and thrombocytopaenia, respectively. Out of these patients, 2 had neutropenic sepsis. Six patients went on to receive maintenance lenalidomide, completing a median of 5 cycles. Only one patient completed the planned 12 months of lenalidomide maintenance; 2 patients discontinued due to infective complications, one due to neutropenia, one due to patient's decision to stop without any adverse events documented, and one due to PD. For the entire cohort, median PFS and OS were 4.7 months and 26 months, respectively. Patients with primary refractory disease (N=7) had a median PFS of only 2 months. When these patients were excluded, the remaining (N=13) had a median PFS of 21 months. Conclusion In our cohort of transplant ineligible R/R DLBCL patients R2-GDP resulted in an ORR of 68%. Patients with primary refractory disease did not benefit from study treatment. However, for the remaining patients, the median PFS of 21 months compares favorably with other salvage regimens in this population. Lenalidomide at 15 mg/day may safely augment RGDP responses in chemotherapy-sensitive relapsed DLBCL. Disclosures No relevant conflicts of interest to declare.

Intrastromal Therapy In-sync with Featured Stereotactic Body Radiotherapy (SBRT)-Fixing the Defiant Tumor Microenvironment-A Proof of Concept Study

The past decade has thrown much light over understanding of tumor micro-environment and its effects on cancer immune evasion. Fibroblasts are resting mesenchymal cells that can be activated to facilitate tissue repair during wound healing. However, cancer associated fibroblasts (CAF) are functionally intense. CAFs can produce growth factors and cytokines such as transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) to promote angiogenesis and recruit immuno-suppressive cells into the tumor stroma leading to immune evasion .Our study targets this resistant tumor stroma using actinium tagged Fibroblast activation protein(FAP) imaging followed by a phased SBRT to one or more sites, Thus by modulating the CAF associated tumor immune-tolerance an improved neo-antigen presentation during SBRT could be expected which may lead to better response rates. The study was started after institutional ethical clearance. A total of 5 patients with disseminated metastatic disease who have had first line therapies and failed subsequently on multiple lines of chemotherapy/targeted therapy were recruited post informed consent. A diagnostic actinium tagged FAP imaging was done and on confirmation of the FAPs tumor site uptake, therapeutic doses of Actinium tagged with FAPs to a dose of 300 micro grams Intravenous. Post 5 days of intra-stromal therapy, SBRT was given in 3 to 5 fractions to the core of all visible metastatic lesions. Patients were assessed for response after 6 weeks with a PET-CT and the side effect profile was assessed with liver function tests, kidney function tests at one-week post completion of SBRT (Stereotactic body Radiotherapy) and also at 6 weeks prior to response assessment PET-CT scan. In all the five patients, there were no observed toxicity with respect to the liver and kidney at 1 week and at 6 weeks post therapy. See Table.Abstract 192; TablePR-Partial response, CR-Complete response, SD-Stable DiseasePrimaryRadiationSiteDoseResponse (RT Site)Response (Distant Site)Patient 1BreastSBRT-3 FractionsBone24GyPRPRPatient 2OvarySBRT-3 FractionsLiver36GyCRPRPatient 3ProstateSBRT-5 FractionsBone35GyPRPRPatient 4ProstateSBRT-3 FractionsProstate24GyPRSDPatient 5LungSBRT-5 FractionsLung30GyPRPR Open table in a new tab Evolution of robust treatment strategies targeting tumor microenvironment is a field of exciting research. Effectively tackling the tumor immune evasion mechanisms based on individual tumor microenvironment profiling such as FAP imaging would ultimately aid in improved response to therapy. The early results of our study are encouraging.

Multi-observer concordance and accuracy of the British Thoracic Society scale and other visual assessment qualitative criteria for solid pulmonary nodule assessment using FDG PET-CT

To compare the interobserver reliability and diagnostic accuracy of the British Thoracic Society (BTS) scale and other visual assessment criteria in the context of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) evaluation of solid pulmonary nodules (SPNs). Fifty patients who underwent FDG PET-CT for assessment of a SPN were identified. Seven reporters with varied experience at four centres graded FDG uptake visually using the British Thoracic Society (BTS) four-point scale. Five reporters also scored SPNs according to three- and five-point visual assessment scales and using semi-quantitative assessment (maximum standardised uptake value [SUVmax]). Interobserver reliability was assessed with the intra-class correlation coefficient (ICC) and weighted Cohen's kappa (κ). Diagnostic performance was evaluated by receiver operator characteristic (ROC) analysis. Good interobserver reliability was demonstrated with the BTS scale (ICC=0.78, 95% confidence interval [CI]: 0.69-0.85) and five-point scale (ICC=0.78, 95 CI 0.68-0.86), whilst the three-point scale demonstrated moderate reliability (ICC=0.70, 95% CI: 0.59-0.80). Almost perfect agreement was achieved between two consultants (κ=0.85), and substantial agreement between two other consultants (κ=0.78) using the BTS scale. ROC curves for the BTS and five-point scales demonstrated equivalent accuracy (BTS area under the ROC curve [AUC]=0.768; five-point AUC=0.768). SUVmax was no more accurate compared to the BTS scale (SUVmax AUC=0.794; BTS AUC=0.768, p=0.43). The BTS scale can be applied reliably by reporters with varied levels of PET-CT reporting experience, across different centres and has a diagnostic performance that is not surpassed by alternative scales.

Safety and Toxicity Profile of Pembrolizumab (PEM) in Combination with ICE Chemotherapy Followed By Autologous Stem Cell Transplantation for Relapsed/Refractory Classical Hodgkin Lymphoma: No Impairment in Stem Cell Mobilization or Engraftment

Background: Despite excellent outcomes in the front-line management of classical Hodgkin lymphoma (cHL), patients with relapsed or refractory disease typically undergo second-line cytotoxic chemotherapy before proceeding to consolidation with autologous hematopoietic stem cell transplant (autoHSCT). Pre-transplant F18-FDG-PET imaging is a well-established predictor of outcomes following autoHSCT; a complete metabolic response (CMR) to second-line therapy defined as a Deauville score 1-3 predicts a favorable outcome and is a requirement for transplant at many centers. The PD-1 pathway plays an important role in the pathogenesis of cHL and checkpoint inhibition with agents including PEM and nivolumab have shown efficacy as monotherapy in heavily pretreated disease. We hypothesized that the addition of PEM to ICE (ifosfamide, carboplatin, and etoposide) chemotherapy will increase the rate of CMR by PET-CT prior to autoHSCT without impairing the mobilization of peripheral blood progenitor cells (PBPC) or engraftment. Here we present interim safety and toxicity data from this ongoing trial (NCT03077828) including the yields of PBPC mobilization and engraftment. Methods: Enrollment criteria include patients age &gt;18 years medically fit for autoHSCT with relapsed/refractory cHL and excludes those with prior PD-1 inhibitor exposure, CNS involvement, more than 2 prior regimens or history of autoimmune disease. Patients are treated with 2 cycles of PEM 200 mg IV on day 1 in combination with ICE chemotherapy (ifosfamide 5000 mg/m2 day 2 CIV over 24hr, carboplatin AUC 5 IV day 2, etoposide 100 mg/m2 IV days 1-3) on a Q21 day cycle. PBPC mobilization and harvest are performed per institutional protocol on recovery post-cycle #2. A cycle of PEM 200 mg IV is then administered as monotherapy followed by response assessment with PET-CT. Patients with Deauville scores ≤3 proceed to autoHSCT per institutional protocol. A third cycle of PEM+ICE is optional following the PET-CT assessment. Neither the conditioning regimen nor management during transplantation is dictated by the protocol. Results: As of July 2019, 23 of 40 planned patients have evaluable safety and toxicity data. One patient had inconclusive pathology and was removed from study after one cycle of PEM-ICE but is included for this report. The median age was 32 (range 19-62) and 17 of 23 patients were females (74%). 8 patients were refractory to first-line therapy, and 9 relapsed within one year of treatment. 19 patients had received ABVD. Following protocol directed therapy, all but one patient had successful mobilization and collection; one had a severe allergic reaction to filgrastim and underwent bone marrow harvest instead. 16 patients collected in a single day of apheresis; the remainder collected within 4 days. The median number of stem cells harvested was 12.6 x 106 CD34+ cells/kg (range 4.2 - 46.1 x 106/kg). 3 patients underwent the 3rd cycle of PEM + ICE chemotherapy. 3 patients had Deauville scores &gt;3 on FDG-PET response assessment; two had biopsies showing only benign processes and proceeded to transplant. Following stem cell reinfusion, all patients successfully engrafted, with a median time to absolute neutrophil and platelet recovery of 11 days (range: 9 - 24) and 12 days (range: 9 - 23), respectively. The combination of PEM + ICE chemotherapy was well tolerated. There were no reports of pneumonitis, colitis, hepatitis, or endocrinopathies. The most common toxicities were cytopenias, mucositis, diarrhea and febrile neutropenia. A single death on protocol was deemed secondary to advanced cardiovascular disease discovered mid-treatment during the patient's pre-transplant assessment. There was no clinical evidence to suggest an inflammatory process resulting in the cardiac arrest. Conclusions: The combination of PEM with ICE chemotherapy in relapsed / refractory cHL appears tolerable and safe. We found no significant hindrance to peripheral blood stem cell harvest and PEM- related AEs were uncommon. Additionally, pre-treatment with a checkpoint inhibitor prior to autoHSCT appears safe thus far and does not appear to delay engraftment. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses. Karmali:Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau. Pro:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Mehta:Millennium/Takeda, Celgene; stock in Celgene, Bristol-Myers Squibb and Bluebird: Speakers Bureau. Gordon:Bayer: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Gilead: Other: Advisory Board; Zylem LLC: Other: co-founder; research in nanoparticles in cancer. Winter:Merck: Consultancy, Research Funding.

Second-look PET-CT following an initial incomplete PET-CT response to (chemo)radiotherapy for head and neck squamous cell carcinoma.

The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a 'second-look' interval PET-CT. Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13weeks (range 6-25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a 'second-look' interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a 'second-look' PET-CT can be used to spare patients unnecessary surgical intervention.