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Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov,NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n=68). Melanoma cell-specific TPH1 and LAT1 expression are significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cut-point survival analysis of pretreatment ‘high’ vs. ‘low’ C11-AMT SUVmaxof the hottest tumor lesion per patient revealed that the ‘low’ C11-AMT SUVmaxwas associated with longer progression-free and OS in our clinical trial (n=26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.

Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.

Purpose Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-FDG-PET parameters before and during definitive radiotherapy with treatment outcomes. Methods and Materials Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an IRB-approved study. 18F-FDG-PET/CT scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method and Cox models were used to estimate the hazard ratios (HR). Results From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intra-treatment SUVmax (normalized to blood pool SUVmean) > 6.7 with intra-treatment SUV40% > 2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HR for RFS and OS (more likely to recur vs less likely) of 7.33 (90% CI 2.97 – 18.12) and 6.09 (90% CI 2.22 – 16.71), respectively and adjusted HR of 6.57 (90% CI 2.53 – 17.05) and 5.61 (90% CI 1.90 – 16.54) for RFS and OS, respectively. Conclusions PET parameters after 2 weeks of definitive radiotherapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.

Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program. The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018–January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8–22; range, 0–66). The median number of CRLMs was 7 (range, 2–40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%. Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.

Purpose To assess whether radiographic and metabolic changes on midchemoradiation therapy (CRT) fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for cervical cancer predict outcome. Methods and Materials Women with International Federation of Gynecology and Obstetrics stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy were enrolled on a single-institution prospective clinical trial; FDG-PET/CT was obtained before CRT and at 30 to 36 Gy. Max and mean standard uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling and competing risk analysis. Results Thirty women were enrolled from 2012 to 2016. After a median follow-up of 24 months, 2-year rates of OS, DFS, DM, NR, and CR were 68% (95% confidence interval [CI], 51%-85%), 44% (95% CI, 26%-63%), 42% (95% CI, 23%-59%), 14% (95% CI, 4%-30%), and 10% (95% CI, 2%-24%), respectively. Intra-PET metrics and TLG across all PET scans were most consistently associated with OS, DFS, DM, and NR on univariate analysis. Intra-CRT TLG was associated with OS (hazard ratio [HR] 1.35; 95% CI, 1.15-1.55; P = .001), DFS (HR 1.19; 95% CI, 1.04-1.34; P = .018), and NR (HR 1.25; 95% CI, 1.10-1.40; P = .002). No absolute or relative changes between parameters of baseline and mid-CRT FDG-PET/CT were associated with disease outcomes on univariate analysis, with the exception of relative change in mean standard uptake values and CR (P = .004). Conclusions In this group of patients with high-risk cervical cancer treated with CRT and brachytherapy, TLG and metabolic tumor volume on intra-CRT FDG-PET/CT was associated with OS. These metrics may provide an early signal for selective treatment intensification with either dose escalation or adjuvant chemotherapy.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A “design, measure, analyze, improve, and control” quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers’ aggregated baseline infiltration rate was 6.2% (range, 2%–16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% (P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates (P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important.

DeltaRex-G is a replication-incompetent amphotropic murine leukemia virus-based retroviral vector that displays a collagen-matrix-targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal ‘dominant negative’, i.e. a truncated construct of the executive cyclin G1 (CCNG1) oncogene. DeltaRex-G inhibits the CCNG1 function of promoting cell competence and survival through the commanding CCNG1/cyclin-dependent kinase (CDK)/Myc/mouse double minute 2 homolog (Mdm2)/p53 axis. In 2009, DeltaRex-G was granted Fast Track designation from the US Food and Drug Administration for the treatment of pancreatic cancer. In 2019, the results of a phase 1/2 study that used DeltaRex-G as monotherapy for stage 4 chemotherapy-resistant pancreatic ductal adenocarcinoma (PDAC) were published. A unique participant of the aforementioned phase 1/2 study is now an 84-year-old Caucasian woman with chemoresistant PDAC who was treated with DeltaRex-G, 3x1011 colony forming units (cfu)/dose, 3 times/week for 4 weeks with a 2-week rest period, for 1.5 years. During the treatment period, the patient's tumors in the liver, lymph node and peritoneum exhibited progressive decreases in size, which were accompanied by a reduction and normalization of serum carbohydrate antigen 19-9 levels, and the patient achieved complete remission after 8 months of DeltaRex-G therapy with minimal side effects (grade 2 fatigue). Henceforth, the patient has been in remission for 12 years with no evidence of disease, no late therapy-related adverse events, and no further cancer therapy following DeltaRex-G treatment. The present study reports a mutation of tumor protein p53 (TP53) (G199V) found retrospectively in the patient's archived tumor samples. TP53 is a well-characterized tumor suppressor gene, and a critical regulatory component of the executive CCNG1/CDK/Myc/Mdm2/p53 axis, which regulates proliferative cell competence, DNA fidelity and survival. Studies are underway to determine whether TP53 mutations in pancreatic cancer can help identify a subset of patients with advanced metastatic cancer with an otherwise poor prognosis who would respond favorably to DeltaRex-G, which would broaden the treatment options for patients with otherwise lethal PDAC.

4004 Background: Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective tumor response. Retrospective and small, prospective studies suggest that the combination of capecitabine and temozolomide is associated with high response rates (RR) and relative long progression-free survival (PFS). This trial was conducted to establish a role for the combination of capecitabine and temozolomide. Methods: E2211 was a multicenter, randomized, phase II trial comparing temozolomide (200 mg/m2 PO QD days 1-5) vs. capecitabine/temozolomide (capecitabine 750 mg/m2 PO BID days 1-14; temozolomide 200 mg/m2 PO QD days 10-14) in patients with advanced pancreatic NETs. Eligibility criteria included: metastatic or unresectable, low or intermediate grade pancreatic NETs, progression within preceding 12 months, and no prior temozolomide, DTIC, capecitabine or 5-fluorouracil. The primary endpoint was PFS; secondary endpoints were Overall Survival (OS), RR, safety, and MGMT as evaluated by immunohistochemistry (IHC) and promoter methylation. Allowing for 5% ineligibility, 145 randomized patients were required to obtain 138 eligible patients to detect a difference in median PFS of 9 versus 14 months (hazard ratio of 0.64) using a two-sided log-rank test at the overall 0.20 significance level with 81% power. Results: 144 patients were enrolled between 4/2013 to 3/2016 to temozolomide (n = 72) or capecitabine/temozolomide (n = 72); the efficacy analysis population included 133 eligible patients. At the scheduled interim analysis in January 2018, median PFS was 14.4 months for temozolomide vs. 22.7 months for capecitabine/temozolomide (HR = 0.58), which was sufficient to reject the null hypothesis for this final primary endpoint (stratified log rank p = 0.022. In the final analysis (5/2021), median OS was 53.8 months for temozolomide and 58.7 months for capecitabine/temozolomide (HR = 0.82, p = 0.42) and RR was 34% for temozolomide and 40% for capecitabine/temozolomide (p = 0.59). Capecitabine/temozolomide was associated with higher rates of grade 3-4 AEs (45% vs. 22%, p = 0.005). MGMT deficiency, defined as either low IHC or positive promoter methylation, was associated with greater odds of response (OR [95% CI] = 6.38 [2.19, 18.60] and 9.79 [1.09, 87.71], respectively). Conclusions: E2211 is the first prospective randomized trial of capecitabine/temozolomide and shows the longest PFS and highest RR reported for patients with pancreatic NETs in a prospective randomized study. MGMT deficiency was associated with greater odds of objective response. Clinical trial information: NCT01824875.

4020 Background: High grade (G3) GEPNENs are a rare and heterogeneous disease entity for which there is little prospective treatment data. EP chemotherapy is the treatment standard but this may not be appropriate for all G3 GEPNEN pts. CAPTEM has demonstrated activity in G3 GEPNENs and may be a promising alternative. EA2142 aimed to determine if CAPTEM was superior to EP in pts with G3 GEPNENs. Methods: This was a multicenter, randomized (1:1) phase II trial for pts with a locally advanced and unresectable or metastatic well differentiated G3 neuroendocrine tumor (NET) or a poorly differentiated, non-small cell G3 neuroendocrine carcinoma (NEC) of suspected gastrointestinal origin and an ECOG PS of 0-2. Pathology must have demonstrated a Ki-67 of 20-100% or at least 10 mitoses/10 high powered field. Pts were randomized to receive capecitabine 750 mg/m2 orally every 12 hours on days 1-14 and temozolomide 200 mg/m2 orally once daily on days 10-14 of a 28-day treatment cycle (Arm A) or etoposide 100 mg/m2 daily on days 1-3 with either cisplatin 25 mg/m2 daily on days 1-3 or carboplatin AUC 5 on day 1 of a 21-day treatment cycle (Arm B). Restaging scans were performed every 8 weeks and toxicity monitored per CTCAEv4. Final statistical plan was to accrue 80 pts to detect a 67% improvement in progression free survival (PFS) (primary endpoint) with CAPTEM as compared to EP, 80% power and one-sided significance level of 0.10. A planned interim analysis for efficacy and futility was conducted. Results: A total of 67 pts were enrolled (Arm A, n=32; Arm B, n=35). Male 58%, African American 4%, Asian 3%. Mean age 61. Among 63 eligible pts, primary tumor site pancreatic 56%, non-pancreatic 43%. Poorly differentiated 57%, well differentiated 33%, unknown 10%. Mean Ki-67 48% (Arm A), 60% (Arm B). The study was closed prior to full accrual due to futility at 57.7% information time. In the interim analysis, among 62 eligible pts, PFS, overall survival and response rate with CAPTEM were 2.43 months (mos) (95% CI 2.04, 7.72), 12.6 mos, 9% respectively vs 5.36 mos (95% CI 2.14, 7.23), 13.6 mos and 10% with EP. Toxicity was evaluable in 57 pts with Grade (G) 3/4 events occurring in 29% of pts on Arm A, 66% of pts on Arm B. G3/4 events occurring in more than 5% of pts on Arm A—febrile neutropenia (n=2); abdominal pain (n=2); diarrhea (n=2); nausea (n=2); neutropenia (n=2); dehydration (n=2) and on Arm B—anemia (n=8); febrile neutropenia (n=2); fatigue (n=2); lymphopenia (n=2); neutropenia (n=12); thrombocytopenia (n=4); leukopenia (n=6). There was one G5 event on Arm A due to sepsis. Conclusions: CAPTEM does not appear to be superior to EP chemotherapy as front-line treatment for pts with G3 NENs but does demonstrate a more favorable toxicity profile. Studies assessing G3 NET independently of G3 NEC are needed. Clinical trial information: NCT02595424.

TPS9591 Background: In patients (pts) with advanced, metastatic melanoma (aMM) anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combination regimens yield durable responses, yet the optimal therapy duration remains unclear. Most prospective studies have treated responding pts for at least 2 years unless there has been a prohibitive treatment related adverse event (TRAE). Durable treatment-free survival has been observed in pts where anti-PD-1 therapy is discontinued after short courses due to TRAEs. Biomarkers are needed to define which pts may safely discontinue anti-PD-1 therapy in order to reduce financial toxicity and risk of late TRAEs, and to improve quality of life. 18FDG-PET/CT scan and tumor biopsy may better assess for active residual disease and identify pts who can safely discontinue treatment. A retrospective study at G-LCCC demonstrated responding pts with aMM who elected to discontinue their anti-PD-1 therapy (median treatment duration 12 months) after a negative PET/CT scan and/or tumor biopsy had event free survival (EFS) of 95% at 3 years (Gibney et al JITC 2021). We hypothesize that pts with disease control by CT scan after 12 months on anti-PD-1 therapy can be safely discontinued from treatment if no hypermetabolic activity on PET/CT scan or negative biopsy for active disease. Methods: EA6192 is a multicenter phase II study to evaluate the EFS after discontinuation of anti-PD-1-based therapy in aMM pts with PET/CT scan and/or biopsy that is negative for active disease. Pts with unresectable stage IIIB-IV aMM treated with nivolumab/ipilimumab (nivo/ipi), nivo, pembrolizumab (pembro), or pembro/ipi are eligible. Pts with uveal melanoma are excluded. Pts must receive 52 weeks of therapy, have disease control (CR, PR or SD by imRECIST) and no prohibitive TRAEs. Eligible pts undergo screening including 18FDG-PET/CT scan at 52 weeks (+/- 2 weeks) from start of anti-PD-1 therapy. Pts with hypermetabolic tumor site(s) undergo biopsy. Pts with non-hypermetabolic PET/CT scan or negative biopsy are assigned to Arm A and are monitored off active treatment. Pts with hypermetabolic PET/CT scan and positive or non-feasible biopsy are assigned to Arm B and remain on active treatment for another 48 weeks. Restaging scans are performed every 12 weeks. Arm B pts with disease control undergo a second PET/CT scan and biopsy, and then are monitored off active treatment. 150 patients are planned for accrual. The primary objective is to accurately define the 12-month EFS rate of Arm A, distinguishing between the null and alternative hypotheses of 12-month EFS rate of 88% and 95% with 92% power and one-sided type 1 error rate of 0.072. Secondary and exploratory objectives include assessment of pathologic response, EFS for Arm B, overall survival, incidence of late TRAEs, and correlative biomarker studies. This study is actively enrolling pts. Clinical trial information: NCT04462406.

TPS4185 Background: Evidence-based data is lacking to guide the care of older adults with newly diagnosed metastatic pancreatic cancer (mPCA). As a result, treatment approach and the selection of chemotherapy regimens are often extrapolated from data from younger patients. Furthermore, vulnerable older adults are often treated with dose adjusted regimens with limited data to support this practice. EA2186 is a phase II randomized controlled trial, and the first prospective study aiming to define the optimal treatment approach of vulnerable older adults with newly diagnosed mPCA. Methods: Patients aged 70 years and over with histologically confirmed pancreatic adenocarcinoma, evidence of metastatic disease, ECOG PS 0-2 and adequate organ function, who are considered vulnerable are eligible for this trial (accrual target 184). This study utilizes a screening geriatric assessment which characterize patients as fit, vulnerable or frail by evaluating functional status, cognition and co-morbidities. Vulnerable patients according to this screening assessment are those with mild abnormalities in functional status, comorbidities and/or cognition, or older than 80 years of age. Those patients will be randomized to receive either modified Gemcitabine/Nab-Paclitaxel or dose-reduced 5-Fluorouracil Leucovorin and Liposomal Irinotecan every 2 weeks. A comprehensive geriatric assessment (GA) and quality of life (QOL) evaluation are completed prior to initiation of therapy for all randomized patients. Follow up will continue until disease progression or withdrawal, with repeated GA and QOL assessments at each disease evaluation. Overall survival is the primary objective, with secondary objectives including progression free survival, and response rate. Enrolled patients will be stratified by age 70-74 vs ≥75, and ECOG PS 0-1 vs 2. Additional endpoints of interest for older adults include: evaluation of risk factors identified through GA, and capturing toxicities of interest for this patient population (i.e. hospitalization, deterioration in PS, and falls). Correlative studies include assessment of pro-inflammatory biomarkers or aging in the blood (IL-6 and CRP) as well as imaging evaluation of sarcopenia and body composition as predictors of treatment tolerance. Clinical trial information: NCT04233866.

Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program.The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%.Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume andPatients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study.From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVPET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.

This retrospective analysis identifies predictors of survival in a cohort of patients with meta-iodobenzylguanidine (MIBG)-positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with 131I-MIBG therapy, to inform treatment selection and posttreatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from 211 P/GEP-NET patients treated with 131I-MIBG between 1991 and 2014. For patients with CT follow-up (n = 125), imaging response was assessed by RECIST 1.1 if images were available (n = 76) or by chart review of the radiology report if images could not be reviewed (n = 49). Kaplan-Meier analysis and Cox multivariate regression estimated survival and progression-free survival benefits predicted by initial imaging, biochemical response, and symptomatic response. Results: All patients had stage IV disease at the time of treatment. Median survival was 29 mo from the time of treatment. Symptomatic response was seen in 71% of patients, with the median duration of symptomatic relief being 12 mo. Symptomatic response at the first follow-up predicted a survival benefit of 30 mo (P < 0.001). Biochemical response at the first clinical follow-up was seen in 34% of patients, with stability of laboratory values in 48%; response/stability versus progression extended survival by 40 mo (P < 0.03). Imaging response (20% of patients) or stability (60%) at the initial 3-mo follow-up imaging extended survival by 32 mo (P < 0.001). Additionally, multiple 131I-MIBG treatments were associated with 24 mo of additional survival (P < 0.05). Conclusion: Therapeutic 131I-MIBG for metastatic P/GEP-NETs appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up help prognosticate expected survival after 131I-MIBG therapy. Multiple rounds of 131I-MIBG are associated with prolonged survival.

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).

Hybrid PET/MR imaging is in early development for treatment planning. This article briefly reviews research and clinical applications of PET/MR imaging in radiation oncology. With improvements in workflow, more specific tracers, and fast and robust acquisition protocols, PET/MR imaging will play an increasingly important role in better target delineation for treatment planning and have clear advantages in the evaluation of tumor response and in a better understanding of tumor heterogeneity. With advances in treatment delivery and the potential of integrating PET/MR imaging with research on radiomics for radiation oncology, quantitative and physiologic information could lead to more precise and personalized RT.

Cardiac single-photon emission computed tomography (SPECT) is often used to identify defects in myocardial perfusion due to atherosclerotic coronary artery disease. It was also used in studies to evaluate radiation therapy (RT)-associated cardiac abnormalities. In the current review, we aim to evaluate the rates of post-RT cardiac SPECT early perfusion abnormalities and relate this to the irradiated left ventricular volume. The studies cited in this systematic review were identified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six studies between 1996 and 2016 fulfilled the inclusion criteria. The reported perfusion defects in these studies were seen in the apical and anterolateral aspects of the left ventricle. Three studies show correlation between the percent of the left ventricle within the RT-field and percent of patients with early perfusion defects on cardiac SPECT. In two studies that used cardiac sparing techniques (such as deep inspiration), that resulted in a low mean heart dose, no perfusion defects were noted. Data suggest that incidental irradiation of the heart in cases of left breast/chest wall RT can result in early post-RT perfusion defects on cardiac SPECT. There appears to be strong dose/volume dependence to the risk, and hence techniques to reduce cardiac exposure are recommended.

Purpose To evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH). Methods and Materials We performed a prospective single-institution single-arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (± internal mammary nodes). The DIBH was done by use of a controlled surface monitoring technique (AlignRT, Vision RT Ltd, London, UK). The RT was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall motion changes were assessed by pre-RT and 6-month post-RT SPECT scans. A cumulative SPECT summed-rest score was used to quantify perfusion in predefined left ventricle segments. The incidence of wall motion abnormalities was assessed in each of these same segments. Results A total of 20 patients with normal pre-RT scans were studied; their median age was 56 years (range, 39-72 years). Seven (35%) patients also received irradiation to the left internal mammary chain, and 5 (25%) received an additional RT field to supraclavicular nodes. The median heart dose was 94 cGy (range, 56-200 cGy), and the median V25 Gy was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities. Conclusions Our results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.

Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT).Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology.This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.

Context Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors. Objective To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG. Design Retrospective chart and imaging review at a tertiary referral center. Patients Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment. Intervention Median 18 800 MBq 131-I MIBG. Main Outcome Measures Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A). Results Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3–6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival. Conclusions Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.

Neuroendocrine tumors (NETs) are relatively rare, with 12,000–15,000 new cases diagnosed annually in the USA. Although NETs are a diverse group of neoplasms, they share common molecular targets that can be exploited using nuclear medicine techniques for both imaging and therapy. NETs have traditionally been imaged with SPECT imaging using 111In-labeled octreotide analogs to detect neoplasms with somatostatin receptors. In addition, certain NETs (pheochromocytomas, paragangliomas, and neuroblastomas) are also effectively imaged using 123I- or 131I-labeled metaiodobenzylguanidine (MIBG), an analog of guanethidine. More recently, PET imaging with 68Ga-labeled somatostatin receptor (SSR) analogs allows neuroendocrine tumors to be imaged with much higher sensitivity. 68Ga-DOTATATE was approved as a PET tracer by the FDA in June 2016. In addition to imaging, both MIBG and DOTATATE can be labeled with therapeutic radionuclides to deliver targeted radiation selectively to macroscopic and microscopic tumor sites. The incorporation of the same molecular probe for imaging and therapy provides a radio-theranostic approach to identifying, targeting, and treating tumors. Over the years, several centers have experience treating NETs with high-dose 131I-MIBG. 177Lu-DOTATATE was approved by the FDA in 2018 for treatment of gastroenteropancreatic NETs and constitutes a major advancement in the treatment of these diseases. In this paper, we provide an overview of imaging and treating neuroendocrine tumors using MIBG and SSR probes. Although uncommon, neuroendocrine tumors have provided the largest experience for targeted radionuclide imaging and therapy (with the exception of radioiodine treatment for thyroid disease). In addition to benefitting patients with these rare tumors, the knowledge gained provides a blueprint for the development of future paired diagnostic/therapeutic probes for treating other diseases, such as prostate cancer.

Nine percent of all primary neoplasms in man are tumors of the central nervous system. The most common brain tumors are astrocytomas; within this group more than half of the tumors are either the malignant anaplastic astrocytomas or the glioblastoma multiforme. Primary brain tumors are ideally suited to localized therapies because they are found in a single area of the brain in more than 90% of the cases. While hyperthermia can be applied noninvasively to the brain, it has the same problem as ionizing radiation in precisely delivering the energy to only the tumor volume. The choice of frequency for an interstitial microwave (MW) antenna array hyperthermia system depends on compromising between a number of factors. Precise temperature measurement is essential for the development and evaluation of interstitial microwave hyperthermia treatments for brain tumors. The microwave antennas and temperature probes left a track that was readily identified histologically.

The objective of this study was to analyze the uptake of rubidium in malignant tumors.Sixteen malignant lesions were included. Two radiologists compared each lesion to four references (subcutaneous fat, lung, mediastinal blood pool, and liver) at rest and stress and scored as 1-4. Maximum standardized uptake value (SUV) in each lesion and four references, as well as ratios of lesion SUV to SUV of each of the references, were calculated at rest and stress. We assessed an agreement for scores of reader 1 versus reader 2 (inter-reader) at rest and stress, scores at rest versus stress (intrapatient) for reader 1 and reader 2, and lesion SUV and respective ratios at rest and stress using paired t-test and Bland-Altman analyses.Fifteen (94%) out of 16 lesions had a score of 3 or 4 at rest or stress or both by at least one reviewer. We did not find evidence of inter-reader bias at rest or stress or intrapatient (rest vs. stress) bias for either reader. SUV ranged from 1.0 to 8.1 at rest and from 0.7 to 6.7 at stress. There was an excellent agreement between ratios of lesion SUV to lung SUV at rest versus stress. On the extreme, there was a poor agreement between ratios of lesion SUV to liver SUV at rest versus stress. Otherwise, the agreement was good for the majority of the results, and moderate for a few others.Malignant tumors can be readily depicted and quantified on rubidium PET/CT. Further research is needed.

TPS5098 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored SOC approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed RT, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive PC. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2ng/mL if within 12 mos of RP) and no metastases on CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes with STAD) are eligible. Prior to study registration, pts undergo SOC baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- metastasis-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of metastasis-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Clinical trial information: NCT04423211.

4064 Background: E/GEJ adenocarcinoma has a high mortality rate despite curative intent therapy. The use of immune checkpoint inhibition is beneficial for treatment of this cancer in the metastatic and adjuvant settings but the role of these agents in the perioperative setting remains unclear. Here we report the results of an initial safety run-in of nivolumab when given in combination with neoadjuvant chemoradiation. Methods: Pts with a localized T1N1-3M0 or T2-3N0-2M0 E/GEJ adenocarcinoma with an ECOG PS of 0-1 and whom were deemed surgical candidates for an esophagectomy by a qualified surgeon were eligible. In step 1, pts were randomized to neoadjuvant therapy with carboplatin AUC 2 and paclitaxel 50 mg/m2 intravenously (IV) weekly x 5 along with 41.4-50.4 Gy radiation without (Arm A) or with (Arm B) nivolumab 240 mg IV during weeks 1 and 3 of treatment, followed by esophagectomy. Pts underwent a second randomization (step 2) to adjuvant nivolumab 240 mg IV every 2 weeks x 12 cycles with or without ipilimumab 1 mg/kg IV every 6 weeks during cycles 1, 4, 7 and 10. For the safety run-in, 30 pts were planned for accrual to allow for 12 evaluable pts per arm. Pts were followed for safety during neoadjuvant therapy through surgery and toxicities monitored per CTCAEv5. Pre-specified early stopping rules were defined to allow halting of the trial if deemed unsafe. Planned study accrual is 278 pts. Neoadjuvant primary endpoint is pathologic complete response rate, adjuvant primary endpoint is disease-free survival. Results: A total of 31 pts were enrolled to the safety run-in element of the study (Arm A, n = 16; Arm B n = 15). Male, 94%; White, 100%; median age, 62; esophageal adenocarcinoma, 52%; GEJ, 48%. Grade (G) 3 events occurring in more than one pt on Arm A—decreased lymphocytes (n = 5). G4 events occurring on Arm A—decreased lymphocytes (n = 1). G3 events occurring in more than one pt on Arm B—decreased lymphocytes (n = 2); anemia (n = 2); leukopenia (n = 4); hypotension (n = 2). G4 events occurring on Arm B—decreased lymphocytes (n = 3); cardiac tamponade and pericardial effusion (n = 1). Cardiac events were thought to be secondary to tumor location, not neoadjuvant treatment. On Arm B, notable G3 events seen in one pt each included colonic obstruction, wound infection and esophageal anastomotic leak. Of pts who have reached the time for surgery, 12/14 pts on Arm A and 13/13 pts on Arm B have proceeded to surgery. Of pts who have completed step 1, 7/14 pts on Arm A and 8/11 pts on Arm B have registered to step 2. Conclusions: The addition of nivolumab to carboplatin, paclitaxel and radiation in the neoadjuvant setting appears to be safe with no disproportionate level of toxicity observed between the two treatment arms. Accrual to the remainder of the trial continues with 43/278 patients accrued. Clinical trial information: NCT03604991.

TPS267 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases (mets) not identified with conventional imaging (CIM). Given greater sensitivity and specificity of PET, its findings are being increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of otherwise non-tailored SOC. Earlier detection of mets with molecular imaging has led to increasing use of focally ablative met-directed RT, to delay or enhance systemic therapy through better local control. There is also interest in earlier use of advanced systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castrate-resistant and metastatic castration-sensitive PC, and potential activity for low-volume mets. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2 if RP within 12 mos), and negative CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes + STAD) and undergo SOC baseline PET are eligible. The study will initially use 18F-fluciclovine but permit additional radiotracers based on FDA approval and availability. Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic mets). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- met-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of met-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified logrank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in experimental arm from 61.5% in control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Trial was activated on October 8, 2020; NCT04423211. Acknowledgement: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180794, U10CA180820, U10CA180868, U10CA180888, U10CA180821, UG1CA233196, UG1CA233253, UG1CA233277, UG1CA233328, and UG1CA233330. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Clinical trial information: NCT 04423211.

Introduction: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. Patients and Methods: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). Results: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. Conclusions: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC. © 2020 Elsevier Inc.In this pilot study, preoperative staging with [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in muscle-invasive bladder cancer detected the primary bladder tumor; however, the determination of lymph node status was limited by few patients with pathologic lymph node involvement. Additional studies are needed to evaluate the potential role for [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in the staging of bladder cancer.

3556 Background: Molecular imaging of metabolic pathways critical for effector T cell response other than glucose could predict response to PD1 inhibitors. We have previously shown that high expression of tryptophan metabolic pathway enzymes in stage III/IV melanoma correlates with reduced abundance of tumor-infiltrating lymphocytes (TILs, ASCO 2019, e21014). Here we investigated C11-AMT, a PET tracer that images tryptophan metabolism, as a predictor of response to pembro in patients (pts) with PD1 inhibitor-naïve MM. Methods: In this trial (NCT03089606) pts must have had measurable MM by RECIST, have undergone IV contrast CT, FDG-PET, and C11-AMT PET scan (30-40 min dynamic imaging), plus a mandatory tumor biopsy prior to pembro treatment. Results: 21 pts (16 males; 15 stage IV; median age 61) had all 3 baseline scans and evaluable research biopsies. 13 pts were non-progressors (CR = 4, PR = 6, and SD = 3). At a median f/u of 13.7 mons (2.8-25.1+), 6 pts are dead from MM, 11 are alive without MM and 4 are alive with MM. 46 tumor lesions were assessed by all 3 scans. Of the pts with tumor lesion, C11-AMT PET SUVmax < 7 and skewness < +0.3 of the tumor lesion with the highest C11-AMT SUVmax was associated with non-progression by RECIST (SUVmax < 7/skewness < +0.3 in progressors vs. non-progressors; Fisher’s 2-tail test p= 0.055). The corresponding association between baseline FDG-PET (SUVmax < 14 and skewness < +0.3) with treatment response was insignificant ( p= 0.08). There was a weak (Spearman ρ= 0.33) but significant correlation ( p= 0.001) in SUVmax between FDG-PET and C11-AMT among the 46 tumors analyzed. There was no significant correlation between melanoma-specific expression of the tryptophan- (TPH1, TPH2, IDO1, TDO2, LAT1) and glucose-metabolizing enzymes (GLUT1, HK1, HK3) by immunohistochemistry. Response to pembro trends to associate with present TILs (Fisher’s p= 0.087). Conclusions: Baseline C11-AMT PET imaging using simple radiomics measures (highest metabolic activity, SUVmax, and tumor heterogeneity, skewness) may better predict clinical benefit from pembro in MM than FDG PET. Variability in C11-AMT’s SUVmax cannot be solely explained by FDG-PET’s SUVmax, suggesting that these two imaging modalities may provide complementary information about intratumoral metabolic dysregulation that may relate with pembro response. Texture analysis using LifeX v4.0 will be presented at the meeting. Clinical trial information: NCT03089606 .

TPS4651 Background: E/GEJ adenocarcinoma has a high mortality rate despite curative intent treatment. A pathologic complete response (pCR) is associated with better overall survival (OS) but occurs in less than 30% of pts. Immunotherapy is effective in the metastatic setting. Here we aim to evaluate the contribution of immunotherapy in the neoadjuvant and adjuvant settings in pts with locoregional E/GEJ cancer. Methods: This is a multi-center, randomized phase II/III trial. Surgical candidates with locoregional E/GEJ adenocarcinoma receive carboplatin AUC 2 IV and paclitaxel 50 mg/m2 IV, both weekly x 5 during concurrent radiation (50.4 Gy) either with or without nivolumab 240 mg IV during weeks 1 and 3, followed by surgery. Pts with no post-operative disease receive nivolumab 240 mg IV every 2 weeks for 12 cycles either with or without ipilimumab 1 mg/kg IV every 6 weeks for 4 cycles. Eligibility criteria include pts with T1-N1-3M0 or T2-3N0-2M0 disease whom are candidates for surgery, no prior chemotherapy or radiation for this disease, no prior immunotherapy, no significant autoimmune disease. Pts must be disease free for adjuvant treatment. Primary neoadjuvant endpoint is pCR rate; primary adjuvant endpoint is disease free survival (DFS). Secondary endpoints include toxicity, DFS and OS. Pre- and mid-treatment diffusion weighted imaging MRI will be conducted during the neoadjuvant portion of the study. A neoadjuvant safety run in of 30 pts is underway. Overall, 278 pts will be needed to detect an absolute improvement of 15% in pCR rate in pts receiving and not receiving neoadjuvant nivolumab and 236 pts will be needed to detect a HR of 0.65 in favor of adjuvant ipilimumab/nivolumab over nivolumab (90% power, one sided alpha of 0.10). Accrual is expected over 34 months at a rate of 8 patients per month. If favorable at interim analysis. Clinical trial information: NCT03604991 .

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.

Background Despite universal adoption of sentinel lymph node biopsy (SLNB) for breast cancer, there remains no standardized protocol for preoperative lymphoscintographic assessment of sentinel nodes. Both immediate and delayed lymphoscintigraphy are currently utilized, although it is unclear how delayed imaging impacts SLN identification. Methods Among patients diagnosed with breast cancer who underwent SLNB at Duke from 2011 to 2012, two protocols for preoperative lymphoscintigraphy were used: protocol A included both immediate and delayed lymphoscintigraphy (n = 152), while protocol B involved immediate lymphoscintigraphy only (n = 103). Results The overall intraoperative SLN identification rate was 98.4% and did not differ between groups. A lower number of SLN were visualized on the immediate scan using protocol A compared to protocol B (P

The purpose of the study was to evaluate the feasibility and protocol optimization of whole-body hybrid MR–PET system performed 1-month after post-locoregional thermoablative procedures for hepatocellular carcinomas (HCCs). Eight patients (6 men and 2 women; mean age, 56.6 ± 5.5 years) with 9 ablated HCCs constituted our study population. Three readers interpreted the studies to determine the presence or absence of residual malignancy. Two readers independently assessed the fused MR–PET images to compare registration accuracy of two types of T2-weighted (triggered T2 half-Fourier acquisition single-shot turbo spin-echo and turbo spin-echo) and T1-weighted [Cartesian and radial 3D gradient echo (GRE)]. Image quality evaluation of both 3D-GRE T1-weighted sequences was evaluated. Kappa statistics were used to measure inter-observer agreement. Non-parametric Kruskal–Wallis and Wilcoxon signed-rank tests were used for qualitative data analysis. Definite residual tumor was observed in 3/9 ablations; two were PET positive. All residual tumors were isovascular on MRI. Radial 3D-GRE demonstrated significantly superior MR–PET subjective co-registration in comparison with the remaining sequences and showed a non-significant trend toward higher image quality scores than Cartesian GRE. Whole-body hybrid MR–PET is feasible as a part of 1-month follow-up post-locoregional thermoablative treatment for HCC. Radial 3D-GRE offers improved co-registration with PET data, with overall good image quality.