Purpose/Objective(s) Greater disease burden is associated with poor outcomes after CAR T. Bridging therapy (BT) is widely used between apheresis and CAR T infusion. We hypothesized that the dynamics of radiomic cytoreduction during the bridging period would be prognostic. Materials/Methods Patients with large B-cell lymphoma (LBCL) treated with CD19 CAR T from 2016–2022 were stratified into 5 BT cohorts: 1) no BT 2) radiotherapy (RT) 3) systemic therapy (ST) 4) ST+RT and 5) steroids alone. All patients had a pre apheresis PET. Patients who received BT also had a repeat PET post BT but pre-CAR T infusion. MTV for all scans was analyzed using a semi-automated method with SUV4 threshold. Progression free (PFS) and overall survival (OS) from CAR T infusion were estimated by Kaplan Meier; multivariable analysis was performed using proportional hazards. Patients were stratified by pre-BT disease burden using an absolute MTV cutpoint of 65.4 cc established by a maximally selected log-rank statistic for PFS. “High” and “low” MTV were defined as MTV above or below this cutpoint, respectively. To quantify the impact of effective cytoreduction during BT, we then created 4 BT MTV risk groups: a) “pLow” with persistently low MTV pre and post BT, b) “pHigh” with persistently high MTV pre and post BT, c) “Rising” with baseline low MTV which increased to high post BT and d) “Improved” with baseline high MTV which decreased to low post BT. Results One hundred ninety-one patients with LBCL (79%), high grade BCL (17%) or primary mediastinal BCL (4%) received CAR T (53% axicabtagene, 22% tisagenlecleucel, 25% lisocabtagene). Forty-seven patients (25%) received no BT, 104 (54%) had ST, 30 (16%) had RT, 5 (3%) had ST+RT, and 5 (3%) steroids alone. Of the 144 patients who received BT, 56% had any degree of quantitative cytoreduction post-BT and only 49% achieved at least 50% MTV reduction. With median follow-up of 21.6 months post CAR T infusion, 12 months PFS was 65% for RT (CI = 47–90%), 50% for no BT (CI = 37–67%), and 39% for ST (CI = 30–50%). Our established MTV cutpoint of 64.5 cc and was significantly associated with PFS (median 20 vs. 2.7 m, P < 0.0001) and OS (unreached vs. 11 m, P < 0.0001). MTV dynamics during BT were further prognostic with 'Improved’ patients having significantly better outcomes vs. the “pHigh” patients with PFS of 11 vs. 2.0 m and unreached vs. 7.2 m OS (P < 0.0001 for both). On multivariate analysis, MTV trajectory across the bridging period remained significantly associated with PFS (P < 0.001); importantly, there was no significant difference in PFS between Improved and pLow patients (HR for Improved = 2.74, CI = 0.82-9.18). Conclusion In our real-world experience, BT was able to reduce disease burden in approximately half of patients. We demonstrate that effective BT can enable initially high disease burden patients to achieve outcomes comparable to low disease burden patients, suggesting BT can convert patients from high to low risk pre-CAR T.

Purpose/Objective(s) High rates of locoregional control are observed after chemoradiation (CRT) for head and neck squamous cell carcinoma (HNSCC), but distant metastasis (DM) remains a major cause of morbidity and mortality. Improved prediction of adverse oncologic outcomes would facilitate patient selection for escalated therapy. Prior studies have shown that tumor hypoxia on FMISO PET predicts for local failure after CRT, but data showing an association with DM are limited. We combined data from two clinical trials to evaluate whether tumor hypoxia on FMISO PET predicts DM-free survival (DMFS) and overall survival (OS) after CRT for HNSCC. Materials/Methods From 2004 to 2020, patients undergoing CRT for nonmetastatic HNSCC who enrolled on two clinical trials investigating the role of FMISO PET (NCT00606294, NCT03323463) were included in this analysis. FMISO PET before and ≥ 7 days after starting CRT were evaluated for tumor hypoxia. Pre- and intra-treatment hypoxia were hypothesized to predict worse DMFS and OS, measured from the end of CRT. DMFS was defined using a composite endpoint, consisting of biopsy-proven HNSCC outside the head and neck or death. Predictors of DMFS and OS were modeled with Cox regression. Results Among 295 patients, 86% had oropharyngeal primaries, and 89% had HPV+ disease. Per AJCC 7th edition staging, 15% had T ≥ 3, and 18% had N ≥ 2c. De-escalated 30 Gy CRT was delivered to 49% of patients; all others received 70 Gy CRT. Pre- and intra-treatment hypoxia on FMISO PET were identified in 218 (74%) and 69 (23%) patients, respectively. Median follow-up among survivors was 4.4 years. DMFS and OS at 4 years were 89% and 94%, respectively. Among 17 patients with DM, 4 had prior locoregional recurrence. Among 69 patients negative for pre-treatment hypoxia, none experienced DM. In univariable models, worse DMFS was associated with pre-treatment hypoxia (HR 3.37, 95% CI = 1.03-11.1, p = 0.04) and intra-treatment hypoxia (HR 2.57, 95% CI = 1.28-5.15, p = 0.008). In a multivariable model, intra-treatment hypoxia independently predicted worse DMFS (HR 2.94, 95% CI = 1.40-6.21, p = 0.005), alongside T ≥ 3 disease. In univariable models, trends toward worse OS were seen with pre-treatment hypoxia (HR 2.76, 95% CI = 0.84-9.08, p = 0.09) and intra-treatment hypoxia (HR 1.76, 95% CI = 0.85-3.61, p = 0.13). Conclusion We report the largest clinical series evaluating tumor hypoxia on FMISO PET as a predictor for DMFS and OS after CRT for HNSCC. Pre- and intra-treatment hypoxia on FMISO PET significantly predicted worse DMFS. Intra-treatment hypoxia predicted worse DMFS independent of tumor stage. No patients who were negative for hypoxia on pre-treatment FMISO PET experienced DM. Tumor hypoxia on FMISO PET may aid in selecting patients for escalated treatment strategies aimed at preventing DM.

HPV-associated oropharyngeal carcinoma (OPC) patients shed viral DNA which has been employed to monitor treatment response. The sensitivity of this approach, however, appears to be limited in OPC patients with low-burden disease. We hypothesized that circulating tumor DNA (ctDNA) detection through personalized tumor-specific alterations in combination with HPV ctDNA offers a more sensitive yet specific approach in early-stage HPV OPC patients. Cell-free DNA (cfDNA) from HPV+ OPC patients enrolled in a phase II chemoradiation (CRT) de-escalation trial (NCT03323563) was collected. All patients underwent resection of the primary tumor before CRT and a baseline plasma was drawn at this time. DNA from the tumor and matched normal underwent whole-exome sequencing to identify somatic variants and for HPV typing. A dual MRD-HPV assay was developed based on the Invitae’s Personalized Cancer MonitoringTM (PCM) assay including personalized tumor-specific and custom HPV-specific primers targeting high-risk HPV types. The MRD-HPV assay was applied to plasma cfDNA samples. 158 patients with T0-2/N1-N2c HPV-OPC were enrolled. The MRD-HPV assay was successfully designed for 111 patients targeting a median of 50 mutations per patient (range: 26-50). 64.0% (71/111) of patients had HPV16-related tumors and available baseline plasma, and all subsequent analyses were conducted on this group. While ctDNA detection by HPV testing resulted in sensitivity of 85.9% (61/71), ctDNA detection by MRD increased sensitivity to 90.1% (64/71). Furthermore, ctDNA detection by either HPV and/or MRD increased sensitivity to 95.8% (68/71). The 10 patients with negative HPV ctDNA tests harbored tumors with lower tumor volume and lower levels of genome instability than HPV ctDNA positive patients. Two of the three patients with negative baseline MRD-HPV had detectable ctDNA within 1 month from the start of treatment. The combination of PCM MRD and HPV ctDNA assays provide a highly sensitive approach for detection of low disease burden in early HPV-associated OPC patients.

Purpose/Objective(s)De-escalation strategies for the treatment of HPV-associated OPC show promise for effective, less toxic treatment. However, identifying accurate markers of more aggressive subsets of HPV OPC remains challenging. The 30 Reduction in Radiation for OPC (ROC) trial prospectively used intra-treatment 18F-FMISO imaging to selectively de-escalate patients to 30Gy chemoradiotherapy, however, a subset of patients still developed nodal recurrence. We hypothesized that diffusion-weighted (DW) MRI-derived quantitative imaging metrics, such as apparent diffusion coefficient (ADC), a surrogate marker of tumor cellularity based on water diffusion patterns, might help identify patients at high risk of recurrence and enable broader use of de-escalation strategies.Materials/MethodsThe 30 ROC trial enrolled patients with p16-positive OPC, cT0-2, N1-2c (AJCC 7th ed). All patients had pre-treatment 18F-FMISO (fluoromisonidazole) PET scan and those with baseline nodal hypoxia underwent a 2nd intra-treatment scan. All patients underwent primary site surgery where negative margin was not required. All patients had gross neck nodal disease. Those with intra-treatment resolution of nodal hypoxia or without initial hypoxia were de-escalated to 30Gy (non-hypoxic group) with 2 cycles of concurrent chemotherapy, while those with persistent radiographic hypoxia (hypoxic group) were treated to 70Gy. Standard T1, T2 weighted, and multiple b-value DW-MRI data were acquired pre-treatment and weekly during the first 4 weeks of treatment. Two radiation oncologists delineated nodal tumor regions of interest (ROIs) in a blinded fashion with ITK-SNAP on DW images (b= 0 s/mm2). Multiple b-value DW data were fitted to a monoexponential model to calculate ADC (mm2/s). The data analysis was performed on ROIs and voxel-wise using the in-house developed tool MRI-QAMPER. Standard statistical analysis was performed using MRI and clinical response data based on RECISTv1.1 provided by a radiologist.Results158 patients were enrolled, of whom 95 had pre-treatment DW-MRI data available with tumor ROI with ADC values. Based on overall 18F-FMISO imaging, 12.6% (12/95) exhibited persistent hypoxia and 87.4% (83/95) had resolved/no hypoxia. All patients with nodal recurrences were in the de-escalated non-hypoxic group (8/83). Pre-treatment ADC was not different between overall hypoxic and non-hypoxic groups. Among de-escalated patients, those who developed nodal recurrence exhibited significantly different intra-treatment ADC at week 3 (before completing 30Gy) relative to those who did not recur (P<0.05, Wilcoxon rank-sum test).ConclusionThe quantitative imaging metric, ADC, reflects both the restricted and hindered Brownian motion of water molecules in tumor tissue. Thus, ADC may be a useful intra-treatment marker to identify patients at risk for nodal recurrence to benefit from the incorporation of an upfront planned neck dissection after 30Gy as part of the de-escalation strategy.

Purpose/Objective(s) F-18 Fluoromisonidazole (FMISO) is a robust imaging biomarker for tumor hypoxia. Hypoxia limits effective cancer treatment, specifically radiotherapy in head and neck cancers. We have completed and have ongoing trials using hypoxia imaging to guide radiation dose de-escalation. To ensure wide applicability, we sought to develop and validate standardized qualitative and quantitative criteria to accurately and reliably interpret clinical FMISO PET/CT images. Materials/Methods All HPV+ oropharyngeal cancer patients who had FMISO PET/CT imaging before and about 2 weeks into chemoradiation therapy and pre-treatment F-18 FDG PET/CT were included. 4 independent nuclear medicine (NM) physicians with varying clinical experience of 1, 3, 5, and 15 years with no FMISO experience interpreted images. Training and reference interpretations were performed by a 5th NM physician with 30 years of clinical and 15 years of FMISO experience. Suspicious cervical lymph nodes (LN) > 1 cm in short axis with abnormal FDG avidity on FDG PET/CT were categorized as positive or negative for FMISO uptake. A LN was considered positive if it demonstrated SUVmax visually greater than floor of mouth (FOM). FMISO SUVmax of the LN and FOM were obtained using a 3D VOI. The training and validation process consisted of: (1) initial instruction; (2) practice interpretation; (3) one on one re-training on contentious group reads; (4) final group training; (5) validation interpretation of new scans. Qualitative, visual comparison of FMISO uptake in LN to FOM, and quantitative, ratio of FMISO SUVmax of LN to FOM, were analyzed. The Fleiss κ coefficient (κ) was calculated to measure inter-reader agreement. Results 192 FMISO scans were included. Qualitative criteria mean sensitivity and specificity (SE/SP) after initial instruction were 0.773 and 0.809. κ was 0.338. Mean SE/SP after additional training were 0.976 and 0.869. κ was 0.864 [95%CI: 0.782 to 0.944]. For the quantitative criteria, ROC curve analysis was used to estimate the best threshold by maximizing the Youden index, which was determined to be SUVmax LN/SUVmax FOM > 1.2. Quantitative criteria mean SE/SP after additional training were 0.896 and 0.953. κ was 0.859 (95%CI: 0.761 to 0.944). The quantitative criteria alone demonstrated a lower sensitivity than the qualitative, 0.896 vs. 0.976. Therefore, we suggest using a hybrid method with quantitative criteria as a guide with the ultimate decision based on qualitative assessment to minimize the number of patients with false negatives and subsequent undertreatment. Conclusion The hybrid qualitative/quantitative diagnostic interpretation criteria developed for evaluating FMISO PET/CT in combination with dedicated training has substantial inter-reader agreement and excellent diagnostic performance. This suggests that multi-institutional studies that employ FMISO PET for patient stratification in prospective trials are feasible and can be implemented.

Purpose/Objective(s)Greater tumor burden before CD19-targeted Chimeric Antigen Receptor T Cell (CAR T) therapy predicts lower complete response (CR) rate and shorter survival. Patterns of failure studies have identified baseline lesion characteristics associated with post-CAR T failure. It is not yet known how bridging radiotherapy (BRT) before CAR T alters outcomes and patterns of failure.Materials/MethodsWe reviewed non-Hodgkin lymphoma patients treated with BRT from 30d pre-apheresis to CAR T infusion from 2016-2021. Metabolic tumor volume (MTV) was determined by manual and semiautomatic methods (concordance correlation coefficient >0.98) using threshold SUV 4 pre-BRT and post-BRT/pre-CAR T; maximally selected log-rank established an MTV cut point of 16cc. Patients were stratified by MTV as 'Poor Risk' (>16cc post-BRT), 'Good Risk' (≤16cc pre- and post-BRT) or 'Converted Risk' (>16cc pre-BRT and ≤16cc post-BRT). Response was evaluated by Lugano criteria. Progression (PD) was classified as pre-existing (present pre-CAR T) vs. new and in field, marginal (within 1cm of), or distant with respect to prescription dose region. Progression free and overall survival (PFS/OS) were measured from CAR T infusion by Kaplan Meier.Results41 patients with diffuse large B cell (DLBCL; n = 33), mantle cell (n = 7) and Burkitt's lymphoma (n =1) were reviewed. 30 (73%) were advanced stage. Most common BRT sites were head/neck (n=14), pelvis (n=7), and extremity (n=7). BRT sites were bulky (≥7.5cm) in 19 (46%), extranodal in 22 (54%), and SUV>10 in 29 (71%). 39% of BRT treated all active disease. Median dose was 30Gy (4 - 54). 17 (41%) also received systemic therapy during the bridging period. Patients received axicabtagene (n=19), tisagenlecleucel (n=10), lisocabtagene (n=9), or brexucabtagene (n=3). In 33 patients with interim PET after BRT: 85% had PR/CR in field (CR=10), 58% had out of field PD. Despite median 13d from BRT to PET, there was a significant reduction in overall max diameter (p=0.006) and SUV (p=0.03) and in field MTV (p<0.001). At median post-CAR T follow up of 20.3mo, 19 DLBCL patients progressed. Most PD (12/19) involved pre-existing sites; 8 were in field/marginal. In DLBCL, median PFS was 20mo; median OS was not reached. In 25 DLBCL patients with post-BRT PET, median PFS was 26, 31, and 2.7mo in Good, Converted, and Poor risk groups. Median OS was unreached for Good/Converted and 11mo for Poor risk.ConclusionBRT significantly reduced maximum diameter, SUV, and MTV – all predictors of poor post-CAR T prognosis. Patterns of failure in this cohort were similar to published failure patterns after CAR T without bridging therapy, which may suggest improved control of higher-risk lesions. Similar PFS and OS in patients with initially low MTV and those who achieved low MTV post-BRT suggests the ability to improve patient risk; larger cohorts are needed to confirm this finding. Greater tumor burden before CD19-targeted Chimeric Antigen Receptor T Cell (CAR T) therapy predicts lower complete response (CR) rate and shorter survival. Patterns of failure studies have identified baseline lesion characteristics associated with post-CAR T failure. It is not yet known how bridging radiotherapy (BRT) before CAR T alters outcomes and patterns of failure. We reviewed non-Hodgkin lymphoma patients treated with BRT from 30d pre-apheresis to CAR T infusion from 2016-2021. Metabolic tumor volume (MTV) was determined by manual and semiautomatic methods (concordance correlation coefficient >0.98) using threshold SUV 4 pre-BRT and post-BRT/pre-CAR T; maximally selected log-rank established an MTV cut point of 16cc. Patients were stratified by MTV as 'Poor Risk' (>16cc post-BRT), 'Good Risk' (≤16cc pre- and post-BRT) or 'Converted Risk' (>16cc pre-BRT and ≤16cc post-BRT). Response was evaluated by Lugano criteria. Progression (PD) was classified as pre-existing (present pre-CAR T) vs. new and in field, marginal (within 1cm of), or distant with respect to prescription dose region. Progression free and overall survival (PFS/OS) were measured from CAR T infusion by Kaplan Meier. 41 patients with diffuse large B cell (DLBCL; n = 33), mantle cell (n = 7) and Burkitt's lymphoma (n =1) were reviewed. 30 (73%) were advanced stage. Most common BRT sites were head/neck (n=14), pelvis (n=7), and extremity (n=7). BRT sites were bulky (≥7.5cm) in 19 (46%), extranodal in 22 (54%), and SUV>10 in 29 (71%). 39% of BRT treated all active disease. Median dose was 30Gy (4 - 54). 17 (41%) also received systemic therapy during the bridging period. Patients received axicabtagene (n=19), tisagenlecleucel (n=10), lisocabtagene (n=9), or brexucabtagene (n=3). In 33 patients with interim PET after BRT: 85% had PR/CR in field (CR=10), 58% had out of field PD. Despite median 13d from BRT to PET, there was a significant reduction in overall max diameter (p=0.006) and SUV (p=0.03) and in field MTV (p<0.001). At median post-CAR T follow up of 20.3mo, 19 DLBCL patients progressed. Most PD (12/19) involved pre-existing sites; 8 were in field/marginal. In DLBCL, median PFS was 20mo; median OS was not reached. In 25 DLBCL patients with post-BRT PET, median PFS was 26, 31, and 2.7mo in Good, Converted, and Poor risk groups. Median OS was unreached for Good/Converted and 11mo for Poor risk. BRT significantly reduced maximum diameter, SUV, and MTV – all predictors of poor post-CAR T prognosis. Patterns of failure in this cohort were similar to published failure patterns after CAR T without bridging therapy, which may suggest improved control of higher-risk lesions. Similar PFS and OS in patients with initially low MTV and those who achieved low MTV post-BRT suggests the ability to improve patient risk; larger cohorts are needed to confirm this finding.

Purpose/Objective(s) The 30 ROC Trial utilizes functional imaging, specifically pre-treatment (Tx) and intra-Tx fluorine-18-labeled fluoromisonidazole positron emission tomography (18F-FMISO PET) to select appropriate human papillomavirus positive (HPV+) OPC patients for major de-escalation to 30 Gy. In this trial, patients also underwent pre-Tx and weekly multiparametric magnetic resonance imaging (MRI) scans to correlate with hypoxia status. The aim of the present study was to assess the value of MRI tumor volume to predict baseline hypoxia status in HPV+OPC patients who underwent major dose de-escalation. Materials/Methods A total (N = 158) patients with cT0-2,N1-2b (AJCC 7th ed.) p16+ OPC were enrolled. All patients had pre-Tx 18F-FMISO PET scans to assess baseline hypoxia status, and only those with baseline hypoxia underwent a repeat intra-Tx scan. Pre-Tx and weekly intra-Tx MRI scans were acquired on technology company's 3T MRI scanner using a neurovascular phased array coil. Radiation oncologists delineated gross nodal disease as regions of interest on T2w images. Tumor volume (cm3) was calculated in ITK SNAP for each patient using the segmentation software. All standard statistical analyses were performed on RStudio 2021.09.2. Results Of the 158 patients, N=95 patients had analyzable pre-Tx and weekly on-Tx MRI scans. Based on pre-Tx 18F-FMISO PET results, increased tumor volume was associated with baseline nodal hypoxia (N=69, median 18.55 cm3, range: 3.15- 60.62) compared to initially non-hypoxic tumors (N= 26, median 6.44 cm3, range: 0.48 – 47.74, p<0.001). After the intra-Tx 18F-FMISO PET result, patients were further stratified into converted negative (N= 57), persistently hypoxic (N=12), and never hypoxic (N=26). We found that the median pre-Tx nodal volume for the persistently hypoxic (median 17.75 cm3, range 5.54- 42.93, p=0.006) and converted negative (median 18.55 cm3, range 3.15 – 60.62, p<0.001) groups was significantly (P= <0.05) increased compared to the initially hypoxia negative patients (6.44 cm3, range 0.48 – 47.74). We performed further assessment of this pattern with intra-Tx MRIs (weeks 1-4) and found that this correlation of groups with baseline hypoxia (converted negative and persistently hypoxic) continued to exhibit larger nodal volume compared to the never hypoxic group. Conclusion Pre-Tx nodal volume on MRI correlates with pre-Tx hypoxia status where the larger the volume, the higher the likelihood of hypoxia. This correlation continued throughout radiation Tx as evidenced by the weekly MRI scans.

Introduction: About 20% of patients with classical Hodgkin lymphoma (cHL) relapse or are primary refractory to first-line treatment and require second-line therapy followed by autologous stem cell transplant. There is no one standard second-line therapy and it is possible that not all patients require such an aggressive approach to achieve cure. Quantitative analysis of baseline 18F-FDG-PET-CT scans could provide a comprehensible risk-assessment complementary to clinical risk-factors. Methods: We analysed baseline 18F-FDG-PET-CT scans from r/r cHL patients treated within three clinical trials with ICE, ICE and brentuximab vedotin (BV) or DHAP and BV. For the clinical risk model we used the following parameters: primary refractory vs relapse, age, Ann Arbor stage and B-symptoms. Metabolic tumor volume (MTV) was calculated using a fixed threshold of standard uptake value (SUV) ≥4.0. Radiomics features were extracted in compliance with the Image Biomarker Standardization Initiative. We developed a predictive model for 3-year time to progression (TTP) using logistic regression with backward selection on robust radiomics features, e.g. SUVpeak (highest 1mL region FDG uptake) and several novel dispersity features, representing dissemination and differences in volume and SUV of lesions within a patient. Results were cross-validated (CV) and validated in an independent external cohort. High-risk groups were defined based on the prevalence of events in the training cohort (22/110; 20%). Results: We included 174 r/r cHL patients; n = 110 in the training set (BV-DHAP and BV-ICE cohort) and n = 64 in the validation set (ICE cohort). The clinical model resulted in an area under the curve (AUC) of 0.81 on the training set (tAUC), CV-AUC of 0.76 and AUC of 0.74 on the validation set (vAUC). Radiomics analysis resulted in a selection of 6 PET features: MTV and 5 dispersity features. The radiomics model showed a tAUC of 0.73, CV-AUC of 0.63 and vAUC of 0.70. Combining clinical and radiomics parameters yielded a tAUC of 0.90, CV-AUC of 0.79 and vAUC of 0.77. Using the combined model on the training set, patients in the high-risk group (n = 22) had a 3-year TTP of 38% vs 90% for patients in the low-risk group (n = 88; p < 0.0001; Fig1A). In the validation set, the 3-year TTP was 39% vs 80% for high- (n = 13) and low-risk patients (n = 51; p = 0.0011; Fig1B). In Fig1C we included an example of PET-CT scans of two patients with stage IV disease and a high and low prediction score. EA - previously submitted to EHA 2021. The research was funded by: SHOW foundation (Amsterdam UMC donation fund to support hematology/oncology scientific research) Keywords: Diagnostic and Prognostic Biomarkers, PET-CT, Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

S. F. Barrington, A. A. Kirkwood, L. C. Pike, C. Guezennec, H. Li, M. le Blanc, D. Poon, M. V. Knopp, L. Clifton‐Hadley, C. Laubach, H. Schöder, J. W. Friedberg, P. W. Johnson Kings College London and Guy's and St Thomas' PET Centre, School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, UK, University College London, Cancer Research UK and University College London Cancer Trials Centre, London, UK, Kings College London, Kings College London and Guy's and St Thomas' PET Centre, London, UK, Kings College London, Kings College London and Guy's and St Thomas' PET Centre, London, UK, Fred Hutchinson Cancer Research Center, SWOG Statistics and Data Management Center, Seattle, USA, Fred Hutchinson Cancer Research Center, SWOG Statistics and Data Management Center, Seattle, USA, Ohio State University, IROC Ohio, Wright Center of Innovation, Columbus, USA, Ohio State University, IROC Ohio, Wright Center of Innovation, Columbus, USA, University College London, Cancer Research UK and University College London Cancer Trials Centre, London, UK, SWOG Cancer Research Network, Operations Office, San Antonio, Texas, USA, Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, USA, University of Rochester, JWF Wilmot Cancer Institute, Rochester, USA, University of Southampton, Department of Medical Oncology, Southampton, UK

Introduction: Management of early-stage follicular lymphoma (FL) is widely variable. We utilized our Follicular Lymphoma Outcomes Database (FLOD) to assess outcomes and understand the role of initial observation in patients (pts) with early-stage FL. Methods: We retrospectively identified 295 pts with grade 1-3A, stage I-II FL diagnosed between 1998 and 2009 at Memorial Sloan Kettering Cancer Center while excluding pts with fully resected disease, incomplete imaging at diagnosis, and pts not prescribed rituximab in frontline systemic therapy. Pts were categorized as immediately treated if localized or systemic treatment was started within 6 months of diagnosis. Pts were stratified by age at diagnosis (years): 20-40 vs. 40-60 vs. 60-75 vs. 75-95, to analyze the percentage of immediate treatment or observation in each group. Results: In the cohort, 137 (46%) pts were initially observed, and 158 (54%) pts received immediate treatment, consisting of radiation (n = 108), systemic treatment (n = 29), or combined modality treatment (n = 21). With a median follow-up of 8.4 years (range 0.3-17.2), the estimated 10-year overall survival (OS) and disease-specific survival (DSS) were 87.2% (95% confidence interval [CI]: 0.83-0.92) and 95.6% (95%CI: 0.93-0.98), respectively. Age at diagnosis did not influence selection of pts for observation or immediate treatment (p value 0.98 and 0.75, respectively for stage I and II pts). In 172 pts with stage I disease, 112 (65%) were immediately treated, while 60 (35%) were observed. In 123 pts with stage II FL, 46 (37%) were immediately treated and 77 (63%) were observed. OS in observed pts was similar to that of immediately treated stage I or stage II pts (hazard ratio [HR]: 1.51, p = 0.41, Fig. A; HR: 0.74, p = 0.48, Fig. D). In stage I or II pts with complete staging with bone marrow biopsy and PET, OS between observed and immediately treated pts remain similar (HR: 4.01, p = 0.10, Fig. B, HR: 0.25, p = 0.17, Fig. E). The median time to first therapy for pts initially observed with stage I and II disease were 4.73 years (95% CI: 2.66-NR, Fig. C) and 6.90 years (95% CI 4.15-NR, Fig. F), respectively. Complete staging did not alter median time to first therapy significantly. PFS for immediately treated pts at 5, and 10 years were 67.6%, and 44.6% for stage I disease, and 46.8%, and 32.2% for stage II disease. Biopsy-proven transformation risk using a competing risk analysis was 4.2% and 10.8% at 5 and 10 years. The research was funded by: P30 CA008748 Keywords: Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract L. Falchi Consultant or advisory role: Genmab. Research funding: Roche, Genmab. P. A. Hamlin Consultant or advisory role: Portola Pharmaceutics, Celgene, Karyopharm, Juno Therapeutics. Research funding: Portola, Molecular Templates, Incyte, J&J Pharmaceuticals. S. M. Horwitz Consultant or advisory role: ADCT therapeutics, Aileron,Corvus, Forty-Seven, Innate Pharma, Kyowa-Hakka-Kirin, Millenium/Takeda, Mundipharma, Portola, Seattle Genetics. Research funding: ADCT therapeutics, Aileron, Celgene, Forty-Seven, Infinity/Verastem, Kyowa-Hakka-Kirin, Millenium/Takeda, Seattle Genetics, Trillium. E. Joffe Consultant or advisory role: AstraZeneca, Epizyme. A. Kumar Consultant or advisory role: Celgene. Research funding: Abbvie, Adaptive Biotechnologies, Celgene, Pharmacyclics, Seattle Genetics. M. J. Matasar Consultant or advisory role: Genentech, Bayer, Merck, Juno, Roche, Teva, Rocket Medical, Seattle Genetics. Honoraria: Genentech, Roche, Bayer, Pharmacyclics, Janssen, Seattle Genetics, GlaxoSmithKline. Research funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics. Educational grants: Genentech, Roche, Seattle Genetics, Bayer. A. J. Moskowitz Consultant or advisory role: Kyowa Hakko Kirin Pharma, Miragen Therapeutics, Takeda Pharmaceuticals, ADC therapeutics, Seattle Genetics, Cell Medica, Bristol-Myers Squibb, Erytech Pharma. Research funding: Incyte, Seattle Genetics, BMS, and Merck. A. Noy Consultant or advisory role: Janssen, Pharmacyclics, Medscape, Targeted Oncology. Research funding: Pharmacyclics, NIH, Raphael Pharma. L. M. Palomba Honoraria: Merck, Celgene, Juno and Pharmacyclics. D. Straus Consultant or advisory role: Seattle Genetics. Research funding: Seattle Genetics. G. von Keudell Research funding: Pharmacyclics, Merck, Epizyme. A. D. Zelenetz Consultant or advisory role: Genentech/Roche, Kite/Gilead, Quant Health, Astra Zeneca; Karyopharm, Adaptive Biotechnology; MorphoSys, JUNO/Celege/BMS, BeiGene, Verastem. Research funding: MEI Pharma, Genentech/Roche, BeiGene, Adaptive BIotechnology. A. Dogan Honoraria: Corvus Pharmaceuticals, Physicians’ Education Resource, Seattle Genetics, Takeda, Roche, EUSAPharma, PeerView. Research funding: Roche and Takeda. G. Salles Consultant or advisory role: Abbvie, Beigene, BMS/Celgene, Debiopharm, Genentech/Roche, Genmab, Incyte, Ipsen, Kite/Gilead, Milteniy, Morphosys, Novartis, Velosbio. A. Younes Employment or leadership position: Employed by AstraZeneca. Consultant or advisory role: Biopath, Xynomics, Epizyme, Roche. Honoraria: Janssen, AbbVie, Merck, Curis, Epizyme, Roche, Takeda. Research funding: Janssen, Curis, Merck, BMS, Syndax, and Roche. C. L. Batlevi Honoraria: Dava Oncology. Research funding: Janssen, Novartis, Epizyme, Xynomics.

Thermal ablation is a minimally invasive technique that is growing in acceptance and popularity in the management of early lung cancers. Although curative resection remains the optimal treatment strategy for stage I pulmonary malignancies, percutaneous ablative treatments may also be considered for selected patients. These techniques can additionally be used in the treatment of oligometastatic disease. Thermal ablation of early lung tumours can be achieved using several different techniques. For example, microwave ablation (MWA) and radiofrequency ablation (RFA) utilise extreme heat, whereas cryoablation uses extremely cold temperatures to cause necrosis and ultimately cell death. Typically, post-ablation imaging studies are performed within the first 1-3 months with subsequent imaging performed at regular intervals to ensure treatment response and to evaluate for signs of recurrent disease. Surveillance imaging is usually undertaken with computed tomography (CT) and integrated positron-emission tomography (PET)/CT. Typical imaging findings are usually seen on CT and PET/CT following thermal ablation of lung tumours, and it is vital that radiologists are familiar with these appearances. In addition, radiologists should be aware of the imaging findings that indicate local recurrence following ablation. The objective of this review is to provide an overview of the expected post-treatment findings on CT and PET/CT following thermal ablation of early primary lung malignancies, as well as describing the imaging appearances of local recurrence. Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Background Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SUR MEAN , SUR PEAK and SUR MAX , respectively. Results Fifteen patients harbored KRAS missense mutations ( KRAS +), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SUR MAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. Conclusion The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

The article 18 F-Fluciclovine ( 18 F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.