Restaging Imaging Research Articles

Targeting BCMA in Plasmablastic Lymphoma: Two Cases of Therapeutic Response to Teclistamab

Plasmablastic lymphoma (PBL) is an aggressive subtype of B-cell Non-Hodgkin lymphoma (B-NHL) with poor outcomes. PBL occurs more commonly in HIV-positive or immunocompromised patients, but it can also occur in immunocompetent patients. Despite anthracycline-based induction therapy, PBL is associated with chemotherapy resistance and early disease relapse, yielding a median overall survival of 7 to 15 months (Castillo JJ, et al. Blood. 2015). The advent of novel therapies altered the therapeutic landscape for many common subtypes of B-NHL, but progress in PBL is lacking due to the rarity of this disease and the lack of effective therapeutic targets. While PBL does not express many common B-NHL markers (e.g. CD19 or CD20), it does highly express B-cell maturation antigen (BCMA). However, data regarding the efficacy of therapies targeting BCMA in PBL is limited. Herein, we report two cases of relapsed/refractory PBL treated with the BCMA-targeting bispecific antibody teclistamab. Patient 1 was a 33 year old male without significant comorbidities when he was diagnosed with Stage IIE PBL after presenting with a chest wall mass. He was treated with six cycles of dose-adjusted EPOCH-V, followed by radiation to the involved region and a BEAM autologous hematopoietic stem cell transplant. Post-transplant imaging showed him to be in a CR on day 30 PET, but he developed recurrent PBL on his day 100 PET exam with osseus lesions. He was then treated with daratumumab and ICE chemotherapy for four cycles, with an initial resolution of osseus lesions. However, he developed relapsed disease with perilymphatic lung nodules. His PBL was confirmed to express BCMA and he was started on teclistamab monotherapy. Following one cycle of weekly teclistamab (1.5mg/kg), his post-treatment PET imaging demonstrated a complete response. He then underwent a consolidative allogeneic hematopoietic stem cell transplant from a matched unrelated donor. As of this report, he remains in a complete response based on his 30 day PET restaging imaging after transplant and without clinical evidence of disease more than 90 days after transplant. Patient 2 was a 60 year old male with medical history of comorbid CAD, stage IV chronic kidney disease, chronic back pain requiring opioid treatment, and peripheral arterial disease when he was diagnosed with Stage IV PBL after he was found to have mass-like thickening of his descending colon on a CT scan. He underwent partial colectomy, with pathology revealing PBL and his post-operative staging PET/CT scan noting osseus, splenic, and hepatic lesions consistent with advanced stage disease. He was initially treated with DA-EPOCH for six cycles with intrathecal methotrexate, which yielded an initial complete response, though he relapsed four months after completing therapy. He was then treated with gemcitabine, oxaliplatin, and daratumumab but progressed after eight cycles on treatment with abdominal and perisplenic masses confirmed on biopsy to be PBL He was then initiated on teclistamab, which was continued weekly. His treatment course was complicated by a viral pneumonia from which he recovered with IVIG and supportive measures. Following 2 total cycles of therapy, his repeat PET/CT imaging was consistent with a complete response (Figure 1), and he remains on weekly teclistamab therapy with no evidence of disease to date. The encouraging responses noted in our two cases illustrate the therapeutic potential of targeting BCMA using teclistamab in PBL. In our cases, teclistamab was a well tolerated therapy, even in our patient with significant comorbidities. This report provides a foundation for future prospective, multicenter clinical trials to evaluate the efficacy and safety of teclistamab in the treatment of relapsed and refractory PBL.

Ultra-High-Resolution T2-Weighted PROPELLER MRI of the Rectum With Deep Learning Reconstruction: Assessment of Image Quality and Diagnostic Performance.

The aim of this study was to evaluate the impact of ultra-high-resolution acquisition and deep learning reconstruction (DLR) on the image quality and diagnostic performance of T2-weighted periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) imaging of the rectum. This prospective study included 34 patients who underwent magnetic resonance imaging (MRI) for initial staging or restaging of rectal tumors. The following 4 types of oblique axial PROPELLER images perpendicular to the tumor were obtained: a standard 3-mm slice thickness with conventional reconstruction (3-CR) and DLR (3-DLR), and 1.2-mm slice thickness with CR (1.2-CR) and DLR (1.2-DLR). Three radiologists independently evaluated the image quality and tumor extent by using a 5-point scoring system. Diagnostic accuracy was evaluated in 22 patients with rectal cancer who underwent surgery after MRI without additional neoadjuvant therapy (median interval between MRI and surgery, 22 days). The signal-to-noise ratio and tissue contrast were measured on the 4 types of PROPELLER imaging. 1.2-DLR imaging showed the best sharpness, overall image quality, and rectal and lesion conspicuity for all readers ( P < 0.01). Of the assigned scores for tumor extent, extramural venous invasion (EMVI) scores showed moderate agreement across the 4 types of PROPELLER sequences in all readers (intraclass correlation coefficient, 0.60-0.71). Compared with 3-CR imaging, the number of cases with MRI-detected extramural tumor spread was significantly higher with 1.2-DLR imaging (19.0 ± 2.9 vs 23.3 ± 0.9, P = 0.03), and the number of cases with MRI-detected EMVI was significantly increased with 1.2-CR, 3-DLR, and 1.2-DLR imaging (8.0 ± 0.0 vs 9.7 ± 0.5, 11.0 ± 2.2, and 12.3 ± 1.7, respectively; P = 0.02). For the diagnosis of histopathologic extramural tumor spread, 3-CR and 1.2-CR had significantly higher specificity than 3-DLR and 1.2-DLR imaging (0.75 and 0.78 vs 0.64 and 0.58, respectively; P = 0.02), and only 1.2-CR had significantly higher accuracy than 3-CR imaging (0.83 vs 0.79, P = 0.01). The accuracy of MRI-detected EMVI with reference to pathological EMVI was significantly lower for 3-CR and 3-DLR compared with 1.2-CR (0.77 and 0.74 vs 0.85, respectively; P < 0.01), and was not significantly different between 1.2-CR and 1.2-DLR (0.85 vs 0.80). Using any pathological venous invasion as the reference standard, the accuracy of MRI-detected EMVI was significantly the highest with 1.2-DLR, followed by 1.2-CR, 3-CR, and 3-DLR (0.71 vs 0.67 vs 0.59 vs 0.56, respectively; P < 0.01). The signal-to-noise ratio was significantly highest with 3-DLR imaging ( P < 0.05). There were no significant differences in tumor-to-muscle contrast between the 4 types of PROPELLER imaging. Ultra-high-resolution PROPELLER T2-weighted imaging of the rectum combined with DLR improved image quality, increased the number of cases with MRI-detected extramural tumor spread and EMVI, but did not improve diagnostic accuracy with respect to pathology in rectal cancer, possibly because of false-positive MRI findings or false-negative pathologic findings.

MRI with diffusion-weighted imaging in staging and restaging of cancer rectum

Abstract Background Magnetic Resonance Imaging (MRI) has emerged as one of the most reliable noninvasive methods for staging rectal carcinoma, due to its ability to precisely delineate rectal tumors. Aim The aim of this study is to assess role of diffusion-weighted (DW) imaging in primary staging and restaging of locally advanced rectal cancers. Patients and methods 40 cases with rectal cancer were included in the research referred to the Radio diagnosis department throughout the period from December 2018 to March 2022. Pelvic MRI with DW imaging was done for all cases. Results According to this studies adding DW imaging to conventional MRI among group I (patients with resectable rectal cancer) increased the diagnostic accuracy to 93.6%, sensitivity to 91%, and specificity to 100%. In group II (patients with locally advanced rectal carcinoma) there was significant increase in the diagnostic accuracy to 83.6%, giving also high negative predictive value as we were able to differentiate between complete responder and nonresponder. Furthermore, the diagnostic accuracy in the evaluation of the mesorectal fascia involvement was much improved after the addition of DW imaging. Conclusion DW imaging yields better diagnostic accuracy than using conventional MR imaging alone in initial staging and restaging of cases with locally advanced rectal cancer.

LUNG-IST-127: A pilot phase II study of maintenance cabozantinib plus pembrolizumab for patients with metastatic squamous non-small cell lung cancer (sqNSCLC) with disease control following induction therapy.

TPS9151 Background: First-line combination chemotherapy with pembrolizumab followed by maintenance pembrolizumab is the standard of care treatment for patients with metastatic sqNSCLC. This was established by the phase III KEYNOTE-407 trial, which demonstrated a median progression-free survival (PFS) of 6.4 months in the experimental arm. Despite these advances, there remains a need to continue to improve upon survival outcomes for these patients. Cabozantinib is a small-molecule inhibitor of multiple tyrosine kinsases including MET, VEGFRs, AXL, RET, and ROS, which are receptors involved in tumor cell-proliferation, angiogenesis, and immune cell regulation. Preclinical studies have demonstrated the ability of cabozantinib to modulate both adaptive and innate immune cells and to exhibit synergistic activity when used in combination with immune checkpoint inhibitors. We hypothesize that cabozantinib in combination with pembrolizumab in the maintenance phase of first-line treatment of metastatic sqNSCLC will prolong median PFS with a tolerable toxicity profile. Methods: LUNG-IST 127 is a pilot phase II, single-arm clinical trial of maintenance cabozantinib in combination with pembrolizumab for patients with metastatic sqNSCLC who achieved disease control following standard 1L induction therapy with chemotherapy and pembrolizumab. Thirty-six patients will be enrolled at 2 US sites to receive first-line induction therapy with carboplatin, nab-paclitaxel or paclitaxel, and pembrolizumab for four cycles. After induction therapy, those who have achieved disease control based on re-staging imaging will continue onto maintenance therapy with cabozantinib 40mg PO daily in combination with pembrolizumab 200mg IV every 3 weeks. The primary endpoint is PFS estimated by Kaplan-Meier methods with associated 95% confidence intervals. Based on an exploratory power analysis using an elevated one-sided alpha level of 0.40, we hypothesize that the proposed therapy will prolong median PFS from 6.4 to 9 months. Key secondary endpoints include overall survival (OS), overall response rate (ORR), and characterizing the safety and tolerability of cabozantinib in combination with pembrolizumab. Quality of life will also be measured with the EORTC QLQ-C30. Correlative endpoints include characterizing cfDNA from biofluids and assessing the change in circulating immune cells in different phases of treatment in association with PFS and OS. This trial would be the first to address whether there is clinical benefit in utilizing combination cabozantinib and pembrolizumab in the maintenance phase of treatment in metastatic sqNSCLC. Clinical trial information: NCT05613413 .

Diagnostic performance of Ga-68 FAPI 04 PET/CT in colorectal malignancies.

To evaluate the role of Ga-68 fibroblast activation protein inhibitor 04 PET/computed tomography (FAPI) in colorectal cancers (CRCs) in terms of diagnostic accuracy and impact on clinical management. FAPI is compared with FDG PET/CT and conventional imaging in staging, restaging, recurrence detection, and response evaluation of CRC. Twenty-nine consecutive patients of histopathologically confirmed primary or relapsed CRC were included in the study. Patients who underwent FAPI PET/CT along with either FDG PET/CT or conventional imaging were included. Primary lesions, recurrence sites, lymph nodes, and metastatic lesions were recorded on all the scans. Maximum standardized uptake value (SUVmax) was measured from both primary and metastatic lesions. The sensitivity of FAPI in primary and recurrence detection is 100% compared to 88% for FDG/conventional imaging. The overall sensitivity of FAPI stands at 98% with accuracy at 95% whereas for FDG/conventional imaging the sensitivity and accuracy are 78% and 77%, respectively, with P < 0.002. Significant difference was noted in the detection of peritoneal metastasis (96% vs. 66%). FAPI PET/CT shows better sensitivity and accuracy in the evaluation of CRCs, especially in peritoneal disease compared to FDG PET/CT and conventional imaging. FAPI has the potential to replace FDG in CRCs.

Determinants of outcome following PSMA-based radioligand therapy and mechanisms of resistance in patients with metastatic castration-resistant prostate cancer.

[177Lu]Lu-PSMA has recently been approved for use in the post-taxane, post-novel hormonal-agent setting in patients with metastatic castration-resistant prostate cancer. As a beta-emitting radioligand targeting prostate-specific membrane antigen (PSMA), it delivers radiation to cells expressing PSMA on their surface. In pivotal clinical trials, patients were selected for this treatment based on positron emission tomography (PET)/CT imaging, requiring PSMA-avid disease with no evidence of discordant disease on 2-[18F]fluoro-2-deoxy-D-glucose PET/CT or contrast CT scan. Despite exhibiting an optimal imaging phenotype, the response for many patients is not durable, and a minority do not respond to [177Lu]Lu-PSMA at all. Disease progression is inevitable even for those who achieve an exceptional initial response. Reasons for both primary and acquired resistance are largely unknown; however, they are likely due to the presence of underlying PSMA-negative disease not identified on imaging, molecular factors conferring radioresistance, and inadequate delivery of lethal radiation, particularly to sites of micrometastatic disease. Biomarkers are urgently needed to optimize patient selection for treatment with [177Lu]Lu-PSMA by identifying those who are most and least likely to respond. Retrospective data support using several prognostic and predictive baseline patient- and disease-related parameters; however, robust prospective data is required before these can be translated into widespread use. Further, early on-treatment clinical parameters (in addition to serial prostate-specific antigen [PSA] levels and conventional restaging imaging) may serve as surrogates for predicting treatment response. With little known about the efficacy of treatments given after [177Lu]Lu-PSMA, optimal treatment sequencing is paramount, and biomarker-driven patient selection will hopefully improve treatment and survival outcomes.

Sarcopenia Prevalence and Influence on the Development of Toxicity and Length of Stay in Patients with Relapsed and Refractory Myeloma Treated with Commercial Anti-BCMA CART Cells

Background Sarcopenic muscle loss has well-documented adverse impacts on treatment outcomes and mortality across cancer types and is particularly prevalent in patients with multiple myeloma, reported in 54% of newly diagnosed patients (Nandakumar ASCO 2022). Two chimeric antigen receptor T-cell (CAR-T) constructs have been FDA approved for relapsed/refractory multiple myeloma (RRMM) after exposure to at least 4 prior lines of therapy. MM Treatment combinations frequently incorporate high dose dexamethasone, well known to cause muscle atrophy, and patients may be on therapy for many years prior to becoming eligible for commercial products with associated detrimental effects from cumulative toxicities. We sought to determine the prevalence of sarcopenia in a real-world cohort of patients with RRMM presenting for commercial CAR-T. Methods We identified all patients presenting to our center treated with commercially approved CAR-T with available restaging imaging performed prior to lymphodepleting chemotherapy (LD-chemo). Cross-sectional area (CSA) of skeletal muscle were measured using Sliceomatic software (v6, Tomovision, 2022), abdominal images obtained from low-dose CT of PET/CT scans, standardized to the midpoint of of the L3 vertebrae. CSA was standardized to the square of patient height to compute skeletal muscle index (SMI, cm2/m2). Patients were categorized as sarcopenic according to international gender-specific consensus cutoffs for SMI, male: < 55.4 cm2/m2 and female: < 38.9 cm2/m2 (Mourtzakis et al, 2008) Patients with the following FISH cytogenetics were considered high risk: t(4;14), t(14;16) and deletion 17p/monosomy 17 whereas the remainder were standard risk. All variables were summarized with descriptive statistics, Mann-Whitney U test, students t-test, chi-squared or Fisher's exact were used where appropriate. Analyses were conducted in Stata (16.1, StataCorp LLC, College Station, TX). Results The cohort consisted of 61 patients, 55 (90%) received ide-cel and 6 (10%) received cilta-cel. Baseline characteristics are summarized in Table 1. Of these 16 (26%) were ≥70 years at the time of treatment and 36 (59%) had co-morbidity index >2 at the time of therapy (Sorror, Blood 2005). All scans were performed a median of 16 days prior to CAR-T administration (range 2-90). Prior to CAR-T administration 47 (77%) of patients met criteria for sarcopenia based on their pre-LD chemo restaging imaging. Male patients were more likely than women to meet criteria for sarcopenia (89% vs 62%, p=0.01) and 31 (50%) met criteria for sarcopenic overweight or obesity. Sarcopenic patients had poorer baseline performance status ECOG >=2 (23% vs 7%, p=0.17), higher baseline ferritin (p=0.08) and higher baseline tumor burden as defined by >50% marrow involvement (40% vs 14%, p=0.08) when compared to non-sarcopenic patients, although not significant at the P=0.05 level. The majority (63%) of sarcopenic patients did not meet criteria for registration trials. No significant relationship was found between the presence of sarcopenia and the development of cytokine release syndrome, but all patients who developed neurotoxicity (any grade) had underlying sarcopenia (any grade ICANS 12/47, 26% vs 0%, p=0.04). A greater proportion of sarcopenic patients had extended lengths of stay >=9 days 51% vs 21%, p=0.05). In total 24/61 (39%) were recommended for post-discharge rehab/physical therapy, of whom the majority (N=20) had baseline sarcopenia. Similarly, 13/61 (21%) required additional supports at home on discharge, N=10 with baseline sarcopenia. Conclusion Sarcopenia is highly prevalent, found in 77% of patients attending for BCMA-directed CAR-T therapy in the commercial setting. We have shown that analysis of body habitus is straightforward to perform using images acquired as standard and could inform practice. In the real-world setting, sarcopenic patients appear to be at higher risk of developing neurotoxicity, although this merits further investigation. Although high prevalence of sarcopenia in this sample may preclude statistical detection of its adverse clinical impacts, it is clearly a significant clinical issue for patients undergoing complex immunotherapies for MM and warrants further research and intervention. Pre-habilitation strategies may be beneficial while patients are awaiting apheresis availability, or during cell manufacturing. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High Metabolic Tumor Volume Is Associated with Higher Toxicity and Decreased Efficacy of BCMA CAR-T Cell Therapy in Multiple Myeloma

Background Recently, two chimeric antigen receptor T-cell (CAR-T) constructs have been FDA approved for relapsed/refractory multiple myeloma (RRMM) after exposure to at least 4 prior lines of therapy. High tumor burden has been associated with inferior outcomes, reduced CAR-T expansion and higher rates of toxicity. Patients relapsing after multiple lines of therapy more frequently have oligosecretory and extra-medullary disease that may not be well captured by serum-based markers of disease or bone marrow infiltration, respectively. Functional imaging with FDG-PET is well established as a useful tool in patients with myeloma but its prognostic impact in highly refractory patients or those proceeding with CAR-T has not been described. Metabolic tumor volume (MTV) capturing all metabolically active disease can be useful as a more global assessment of disease burden. We sought to evaluate tumor burden as measured by MTV in a cohort of patients presenting for anti-BCMA CAR-T with RRMM. Methods We identified all patients presenting to our center treated with anti-BCMA CAR-T with available restaging imaging performed within 60 days prior to lymphodepleting chemotherapy (LD-chemo). Baseline skull to midthigh with or without leg/whole-body 18F-FDG PET/CT scans were evaluated for MTV using a custom tool implemented on MIM PACS version 7.1 (MIM Software, Cleveland, OH) as previously reported (Dean et al, Blood Adv 2020). Briefly, images were semi-automatically analyzed to identify abnormal regions with reference to average metabolic activity of normal liver defined by PET SUV. Metabolically active volume at the lesion level were converged based on PERCIST criteria (41% of SUVmax). Summation of the metabolically active volumes across the human body is reported as the Metabolically Tumor Volume (MTV), measured in ml. Patient image scans were reviewed centrally by a radiologist blinded to outcomes, who removed any false positive uptake unrelated to metabolically active disease. Patients with the following FISH cytogenetics were considered high risk (HR): t(4;14), t(14;16) and deletion 17p/monosomy 17 whereas the remainder were standard risk (SR). The high and low tumor volume groups were selected based on the median MTV value in cohort. Baseline laboratory tests (e.g. beta2 microglobulin (b2M), C-reactive protein (CRP)) and repeat bone marrow biopsy were obtained prior to LD-chemo. Soluble BCMA (sBCMA) was measured by ELISA on patients with available serum samples (R&D Systems, MN, USA #DY193). All analyses were conducted in Stata (16.1, StataCorp LLC, College Station, TX). Results The study cohort consisted of 66 patients. Median age was 65 years (range 36 - 81), 55% were male, 55% had ECOG 0-1 prior to LD-chemo and 65% received bridging therapy. 25 (38%) were categorized as HR based on FISH cytogenetics. Patients had received a median of 6 prior lines of therapy and median interval between PET and date of CART infusion was 14.5 days (range 2-54). Median MTV was 26.3ml (0.26-1073.87ml) and only 3/66 (5%) had no measurable PET-avid lesions captured by this algorithm. Patients with high MTV (>26) were more likely to have elevated baseline CRP >0.5mg/dL (p=0.007) and receive bridging therapy (60% vs 40%, p=0.02). MTV correlated with sBCMA levels on day -6 (r=0.82, p=0.003), and with baseline b2M (r=0.47, p=0.005), but MTV did not correlate well with percentage plasma cells in pre-CAR-T bone marrow biopsy (r=0.12, p=0.3). The risk of ³G2 CRS was significantly higher (44% vs 12%, p=0.02) and any grade ICANS was numerically higher (27% vs 12%, p=0.1) in those with high vs low MTV, respectively. Finally, fewer patients with high MTV achieved CR by D30 (19% vs 31%, p=0.2) and with limited follow up 12/14 (86%) of deaths had occurred in patients with high baseline MTV (p=0.003). Conclusion These preliminary data confirm the added value of MTV calculated from baseline imaging as part of standard of care in patients with heavily pre-treated relapsed myeloma presenting for anti-BCMA CAR-T therapy. MTV correlated highly with sBCMA measured at day-6 and may be more representative for risk assessment than basing burden on bone marrow plasma cell percentage, which has not demonstrated a consistent relationship in predicting adverse events to date. High MTV appears to be associated with an increased risk of CAR-T specific adverse events and inferior outcomes and warrants further investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

172P Impact on management of non-metastatic prostate cancer biochemical recurrence with use of 68Ga PET-PSMA PET/CT scans in single-institution experience

68-Ga PSMA PET/CT has become a new reference standard for prostate cancer (Pca) imaging beyond conventional techniques. This study aims to compare the role of 68-Ga PSMA PET/CT and conventional imaging for staging and re-staging in nonmetastatic Pca who have biochemical Recurrence and evaluate the impacts on management.

Incidence of Brain Metastasis as First Event in Patients with Esophageal Carcinoma: a Report from Three Prospective Alliance Clinical Trials.

Historically, reported incidence of brain metastasis secondary to esophageal carcinoma is low. We sought to determine the incidence of brain metastasis in a contemporary cohort of patients with carcinoma of the esophagus. Data from patients with localized esophageal carcinoma prospectively enrolled on three curative intent Alliance treatment trials (N0044, N0342, N044E) were reviewed including time to diagnosis of first progression event (brain versus other site) and overall survival. Eighty-five patients comprised the cohort of which 85% were male and 86% had adenocarcinoma primary tumor histology. Thirty-nine of the 85 patients had documented progression to any site, and of those, brain metastasis occurred as the first event in 15% (6 of 39). Adenocarcinoma was the primary histology in all 6 patients and tumor grade was high (3 or 4) in 5 of the 6 patients (one not documented). Median time to brain metastasis (9.6months) versus non-brain metastasis (12.4months) and median survival after first progression (5.4months versus 8.1months, respectively) were not statistically different. In this prospective cohort of patients with esophageal carcinoma, those with high-grade adenocarcinoma appear to have a higher incidence of brain metastasis than historically reported. The pattern of brain metastases corroborates recent findings in terms of incidence, predominance of adenocarcinoma primary tumor histology, timing after diagnosis, and overall survival. Further study to confirm these findings, as well as the value of baseline, restaging and follow-up cranial imaging for brain metastasis is recommended. NCT00022139 (NCCTG N0044), NCT00100945 (NCCTG N0342), and NCT00100945 (NCCTG N044E).

Recommendations for radiation therapy in oligometastatic prostate cancer: An ESTRO-ACROP Delphi consensus

Background and purposeOligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospective randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices. Material and methodsA European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists’ experts in prostate cancer was asked to answer a dedicated questionnaire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer. ResultsThe panel achieved consensus on patient selection and routine use of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligoprogressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented. ConclusionThese recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of randomized trials are available.

Clinical importance of second-opinion interpretations of abdominal imaging studies in a cancer hospital and its impact on patient management

PurposeThe purpose of this retrospective study was to evaluate the quality of outside hospital imaging and associated reports submitted to us for reinterpretation related to clinical care at our tertiary cancer center. We compared the initial study interpretations to that of interpretations performed by subspecialty-trained abdominal radiologists at our center and whether this resulted in a change in inpatient treatment. Materials and methodsWe performed an institutional review board-approved retrospective single-institution study of 915 consecutive outside computed tomography (CT) and magnetic resonance (MR) abdominal imaging studies that had been submitted to our institution between August 1, 2020 and November 30, 2020. The assessed parameters included the quality and accuracy of the report, the technical quality of the imaging compared to that at our institution, the appropriateness of the imaging for staging or restaging, usage of oral and IV contrast, and CT slice thickness. Clinical notes, pathologic findings, and subsequent imaging were used to establish an accurate diagnosis and determine the effect on clinical treatment. Discrepancies between the initial and secondary interpretations were identified independently by a panel of radiologists to assess changes in treatment. The impact of discrepancies on treatment was evaluated based on current treatment guidelines. ResultsOf 744 CT (81%) and 171 MR (19%) outside imaging studies, 65% had suboptimal quality compared to the images at our institution, and 31% were inappropriate for oncological care purposes. Only 21% of CT studies had optimal slice thickness of <3 mm. Of 375 (41%) outside reports, 131 (34%) had discrepancies between secondary and initial interpretations. Of the 88 confirmed discrepant studies, 42 patients (48%) had a change in treatment based on the secondary interpretation. ConclusionsImaging studies from outside institutions have variable image quality and are often inadequate for oncologic imaging. The secondary interpretations by subspecialty-trained radiologists resulted in treatment change.

HELIX-ICC: An-open label phase II trial of induction systemic mFOLFIRINOX followed by concurrent hepatic arterial infusion of floxuridine and systemic mFOLFIRI for unresectable intrahepatic cholangiocarcinoma.

TPS500 Background: The majority of patients with intrahepatic cholangiocarcinoma (ICC) present with advanced liver dominant disease rendering them unresectable. The current standard of care supports palliative treatment of unresectable ICC with gemcitabine plus cisplatin. Alternatively, continuous liver-directed therapy using a surgically implanted hepatic arterial infusion (HAI) pump allows for maximal treatment of liver tumors with limited systemic side-effects and can facilitate conversion to a resectable status. No prospective clinical trial has utilized FOLFIRINOX in combination with HAI floxuridine-dexamethasone for ICC. Methods: HELIX-ICC is a first-line, single-center, single-arm, phase II clinical trial enrolling patients with liver-dominant unresectable or multifocal ICC. Only patients with microsatellite stable cancer and no prior liver radiotherapy will be included. Patients are administered dose-modified FOLFIRINOX systemically for 4 cycles over 8 weeks. Those with evidence of disease control on restaging imaging and laparoscopy will proceed to HAI pump placement. Treatment continues with two 28-day cycles of combined HAI floxuridine (1.08 mg/kg) with dexamethasone for 14 days and systemic dose-modified FOLFIRI starting on day 15. The primary objectives are to evaluate the safety and efficacy (disease control rate [DCR] at 6 months) of this novel treatment approach that utilizes our institutional dose-reduced HAI floxuridine protocol in combination with modified systemic regimens to facilitate control of liver disease and maximize patient quality of life (QoL). HELIX-ICC includes many exploratory analyses through longitudinal collection of blood samples, liver biopsies (including an end of trial research biopsy), and QoL metrics (Table). The study is open to n = 30 with an initial safety run-in of 6 patients, of which 4 have enrolled at the time of submission. This study is designed to allow for drop out of 9 patients, with total accrual of 21 patients to protocol completion achieving 80.2% power at 0.05 significance to detect a 25% increase in DCR at 6 months. Clinical trial information: NCT04251715. [Table: see text]

Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging.

Objective responses to first-line systemic chemotherapy in metastatic pancreatic cancer patients are seen in less than one third of cases. Unfortunately, a significant amount will have disease progression (PD) on their first restaging imaging. With patients' short life expectancy, it is crucial for clinicians to be prudent when deciding whom and when to treat. Our study aimed to evaluate outcomes of patients that progressed on their first restaging imaging on 1st line therapy. We retrospectively analyzed patients diagnosed between 2010-2017 whose first restaging imaging demonstrated PD. The primary outcome was overall survival (OS) from metastatic diagnosis date to death. Patients who were lost to follow-up were excluded. Out of 262 total patients reviewed, 98 patients (37%) were included. Sixty-five (66%) received 2nd line therapy, and 33 (34%) did not. Reasons patients did not pursue 2nd line therapy were performance status (PS) decline, organ dysfunction, or patient choice for alternative therapy. Median ages for patients who did and did not receive 2nd line therapy were 61 and 67, respectively (P<0.001). More patients had a poor PS at the time of initial diagnosis in the non-2nd line therapy group (7.5% vs. 31.0%, P=0.021). Median OS for those receiving 2nd line therapy was 9 months (95% CI: 7-11 months) compared to 4 months (95% CI: 3-5 months) for those not receiving 2nd-line therapy (P<0.001). Although likely biased due to better performance status and younger age, our patients who progressed rapidly on 1st line therapy showed an OS benefit if they received 2nd line therapy. These results suggest that patients maintaining a good PS after immediate progression on 1st line therapy should be offered 2nd line therapy.

Update on the Role of Imaging in Clinical Staging and Restaging of Renal Cell Carcinoma Based on the AJCC 8th Edition, From the AJR Special Series on Cancer Staging

Update on the Role of Imaging in Clinical Staging and Restaging of Renal Cell Carcinoma Based on the AJCC 8th Edition, From the AJR Special Series on Cancer StagingAsser Abou Elkassem, MD1, Brian C. Allen, MD2, Kedar G. Sharbidre, MD1, Soroush Rais-Bahrami, MD1,3 and Andrew D. Smith, MD, PhD1Audio Available | Share Claim CREDIT

Pseudoprogression and cancer immunotherapy: A seven year retrospective study of rate, temporal course, and predictive markers in an Irish tertiary referral center.

2651 Background: Immunotherapy is a relatively new treatment strategy which has achieved unprecedented clinical efficacy in many advanced malignancies. However, the pattern of tumour response to immunotherapy is distinct from other therapies and poses major challenges to clinicians. One such challenge is pseudoprogression. The aim of this study was to assess the current management of patients on immunotherapy with radiological evidence of disease progression at first restaging imaging in an Irish cancer centre, and to determine the rate, time course, and predictive markers of pseudoprogression in those patients treated beyond progression (TBP). Methods: Patients treated with immunotherapy for metastatic malignancy in MMUH between March 2013 and September 2020 were retrospectively drawn. Inclusion required follow-up restaging imaging every 4-12 weeks for the duration of treatment. Patterns of response during immunotherapy were established from radiology reports and categorized as stable (SD), response (R), mixed disease (MD), or progressive disease (PD). Pseudoprogression was defined as progression/ mixed disease at first restaging compared to baseline followed by subsequent response/stable disease. Results: The cohort of 228 patients was comprised of 80 NSCLC, 74 melanoma, 25 RCC, 19 gynaecological, 14 gastrointestinal, 6 breast, 1 ESSCLC, and 9 other cancer patients. Median age was 61.16 (IQR 49.47-69.44). Therapeutic agents were anti-PD1 alone (176) or in combination with targeted therapy (6) or CTLA4 (13), CTLA4 alone (15), and anti-PD-L1 alone (13) or in combination with chemotherapy (5). At first restaging, the number (%) classified as SD, R, MD, and PD, respectively, was 29 (12.8), 62 (27.2), 16 (7), and 76 (33.3). Treatment was stopped prior to restaging in 44 (19.3) cases. Of the 92 patients with mixed/ progressive disease, 41 were TBP and 51 were not treated beyond progression (NTBP). Evidence of radiological progression and worsening performance status (PS) were the most common reasons given by clinicians for NTBP. Of those TBP, 20 had subsequent response/stable disease, occurring at a median of 105.50 (range 58.0-420) days after the initial restaging scan and giving an overall pseudoprogression rate of 8.8%. At one year, 100% of the pseudoprogression group was alive. The neutrophil-lymphocyte ratio (NLR) was significantly lower in the pseudoprogression group compared to those with true progression (p = 0.006). There was no significant difference in performance status between the two groups. Conclusions: Pseudoprogression on cancer immunotherapy is real but uncommon, with an overall incidence of 8.8%. It can occur any time up to 420 days after initial progression and indicates a high likelihood of &gt; 1 year survival. A low NLR may be a useful predictor of pseudoprogression but a technological solution is likely needed.

MRI and targeted biopsies compared to transperineal mapping biopsies for targeted ablation in recurrent prostate cancer after radiotherapy: Primary outcomes of the FORECAST trial.

5009 Background: Radiotherapy is a common and effective treatment for localised prostate cancer. However, recurrence of cancer can occur in 10-15% of men in the following 5 years. Most patients with recurrence are managed using hormonal therapy with associated systemic side-effects and subsequent development of castrate resistance. Salvage prostatectomy confers a high risk of urine incontinence and rectal injury. Accurately localising and ablating only areas of recurrence within the prostate might be effective with fewer side-effects. The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial assessed this diagnostic and treatment pathway for men with radiorecurrent cancer (NCT01883128). Methods: We first compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy (Apr/2014-Jan/2018) in 181 patients from 6 UK centres. We then assessed the functional and cancer control outcomes of focally ablating areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU). Primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies and urinary continence after focal ablation. A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment. Results: Of 181 men with suspicion of recurrence following radiotherapy, re-staging whole-body imaging (Choline PET and Bone Scan) showed localised disease in 128 (71%), nodal disease only in 13 (7%) and 38 (21%) metastatic. The sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%). Specificity, and positive and negative predictive values, were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%). 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone. Overall sensitivity of mpMRI was 81% (95%CI 73-88%) using Likert score 4-5 to denote a positive test. Specificity, and positive and negative predictive values, were 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%). In the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%); 5/93 (5%) had a CTCAE grade 3+ adverse events. There were no rectal injuries. With a median follow-up of 27.8 [SD 1.3] months, PFS was 66% [54-75] at 24-months. Metastases-free survival in the 73 men with localised disease was 80% [95%CI 68–88] at 24-months. There were no cancer specific deaths. Conclusions: Prostate mpMRI and MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Focal ablation to areas of intra-prostatic recurrence preserves continence in the majority of men with good cancer control. Clinical trial information: NCT01883128.

Encorafenib and binimetinib with or without nivolumab in treating patients with metastatic radioiodine refractory BRAF V600 mutant thyroid cancer.

TPS6085 Background: Differentiated thyroid cancer is the most common endocrine malignancy and has a high frequency of actionable molecular aberrations including BRAF V600E mutations (45%), RET fusions (10%), and NTRK fusions ( &lt; 2%). FDA approved systemic therapies for metastatic radioiodine refractory differentiated thyroid cancer (RR-DTC) include multikinase inhibitors (Lenvatinib and sorafenib), NTRK inhibitors (larotrectinib and entrectinib for NTRK fusion+ cancers), and RET inhibitors (selpercatinib and pralsetinib for RET fusion+ cancers). Previous phase II clinical trials showed clinical efficacy with first and second generation BRAF inhibitors in patients with BRAF mutant RR-DTC. BRAF inhibitors have not yet been FDA approved for treatment of BRAF mutant RR-DTC. Effective therapeutic options for patients with BRAF mutant RR-DTC remains an important unmet clinical need. BRAF mutant thyroid cancers often show elevated expression of PD-L1. Additionally, BRAF inhibition results in increased expression of PD-L1 in thyroid cancer. This clinical trial seeks to evaluate the safety and efficacy of encorafenib plus binimetinib with or without nivolumab in patients with BRAF mutant metastatic RR-DTC. Encorafenib and binimetinib are highly selective and potent oral inhibitors of BRAF and MEK, respectively. Nivolumab is a potent inhibitor of the immune co-inhibitory receptor programmed cell death protein 1 (PD-1). Methods: This is a phase II, single institution, open-label, randomized clinical trial evaluating the combinations of (Arm 1) encorafenib 450 mg/day + binimetinib 45 mg twice daily and (Arm 2) encorafenib 450 mg/day + binimetinib 45 mg twice daily + nivolumab 480 mg I.V. every 4 weeks in patients with metastatic BRAF mutant RR-DTC. The trial will enroll 20 patients in each arm and treatment will be given in 28 day cycles for up to 2 years. Eligible patients must have metastatic/unresectable BRAF mutant RR-DTC, an ECOG performance status of 0-1 and adequate bone marrow, liver and kidney function. Patients with CNS metastases are included if the metastases have been treated and remained stable or are asymptomatic and ≤10 mm in diameter. Patients may be systemic therapy naïve or have previously been treated with multikinase inhibitors. Prior therapy with BRAF, MEK or immune checkpoint inhibitors is exclusionary. The primary endpoint is confirmed objective response rate (ORR) determined by RECIST v1.1 with restaging imaging every 12 weeks. Secondary endpoints include progression free survival, overall survival, and safety/tolerability (CTCAE v5.0). Arms 1 and 2 will be evaluated independently and are not powered for direct comparison. The trial design includes continuous toxicity monitoring with a Pocock-type stopping boundary. This clinical trial is in progress and 3 patients have been enrolled. Clinical trial information: NCT04061980.

Equivalent tumor detection for early and late FAPI-46 PET acquisition

IntroductionPositron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer.MethodsThis is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33).ResultsIn total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: − 0.48, − 0.14, − 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03).ConclusionIn conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

Neoadjuvant chemotherapy for resectable oncologically high-risk biliary tract cancers

Presenter: Kelvin Allenson MD | Moffitt Cancer Center Background: Surgical resection for biliary tract cancers (BTC) remains the only curative therapy, yet recurrence rates following resection remain high. Prior retrospective studies have identified clinicopathologic features that are associated with high risk of recurrence. A neoadjuvant chemotherapy (NAC) approach for high-risk BTC may select patients with more favorable tumor biology, treat micrometastatic disease and decrease the risk of recurrence, although this approach has not yet been examined in prospective clinical trials. The purpose of this study was to evaluate the safety and outcomes of a NAC approach in resectable oncologically high-risk BTC. Methods: A hepatobiliary disease-site-specific multidisciplinary tumor board was created at a major comprehensive cancer center in November 2015. Diagnosis, stage, pertinent imaging findings and treatment recommendations are prospectively recorded. Tumor board records were reviewed from November 2015-May 2020 to identify patients with resectable, oncologically high-risk BTC for whom a NAC approach was recommended. These patients were cross-referenced with the prospectively maintained hepatobiliary surgery database to ensure that all patients were captured. Patients who underwent abdominal exploration/aborted surgical resection prior to initiation of chemotherapy were excluded. Patients who met the inclusion criteria composed the intention-to-treat (ITT) cohort, while those patients who met the inclusion criteria and received NAC, composed the NAC cohort. Results: Fifteen patients were identified who had resectable oncologically high-risk BTC and recommended to undergo NAC. Three (20%) patients were lost to follow-up, and to the best of authors’ knowledge never started NAC, while the remaining 12 (80%) received NAC. The mean age of the ITT cohort was 64 years old, 12 (80%) had a Charlson Comorbidity Index of 2-3. Nine (60%) patients had intrahepatic cholangiocarcinoma (IHCC) and 6 (40%) had gallbladder cancer (GBC). In the NAC cohort, the median number of chemotherapy cycles was 4; 11 patients received gemcitabine/cisplatin and 1 received FOLFOX. Ten of 12 patients underwent oncologic resection, while the other 2 patients (1 IHCC and 1 GBC) had evidence of disease progression on re-staging imaging. One of 10 patients who underwent surgical resection had a Clavien-Dindo grade 3/4 complication (percutaneous drain for a seroma). On final surgical pathology, 2 IHCC patients had pathologic upstaging, while 3 of 4 gallbladder cancer patient had no residual disease. Eight of 10 patients who underwent surgical resection received additional postoperative chemotherapy. With a median follow up of 19.9 months, the median progression free (PFS) and overall survival (OS) in the ITT cohort was 11.7 and 16.9 months, respectively. In the NAC cohort, PFS and OS was 15.8 and 20 months respectively. Conclusion: In this retrospective study of NAC in resectable oncologically high-risk BTC, 67% and 83% of the ITT and NAC cohorts received NAC and surgical resection. Only 1 significant perioperative complication was observed. Although NAC for BTC remains investigational, it was well tolerated, did not appear to increase surgical morbidity and resulted in reasonable oncologic outcome (median OS 20 months). Randomized trials investigating a NAC approach for oncologically high-risk BTC are warranted.