PET Criteria Research Articles

Quantitative‐ and visual read‐based flortaucipir PET T+ criteria for the pathophysiological assessment of Alzheimer’s Disease

AbstractBackgroundThe revised NIA‐AA biological Alzheimer’s disease (AD) staging scheme considers various tau positivity (T+) rules based on global and regional neocortical tau PET uptakes. In AD clinical trials, various tau PET criteria (e.g., visual+quantitative [TauVQ], Mintun et al., 2021) have been employed to select eligible patients. In this study, we compared six T+ criteria in terms of their potential usefulness for biological staging and clinical trial eligibility.MethodsN=296 symptomatic (189/107 MCI/AD‐dementia) subjects from AV‐1451‐A05 (NCT02016560) were included. Six different tau‐PET stratifications (T+/T‐) were employed: Two quantitative global neocortical uptake measures (CenTauR‐Universal, Villemagne et al., 2023, and AD‐signature weighted neocortical, Devous et al., 2018); two quantitative temporal‐based uptake measures (CenTauR‐Meta‐temporal, Villemagne et al., 2023 and Early Tau VOI, Kotari et al., 2023), a visual read‐based method (Fleisher et al., 2021) and TauVQ method. A dataset of young cognitively normal subjects (N=16) was utilized to determine T+ thresholds for quantitative measures (mean+2.5xSD SUVr). The tau stratifications were evaluated for their agreement with amyloid‐PET positivity and for AD‐related prognostic utility using signal‐to‐noise ratios (SNRs) of T+ for (1) Annualized change in AD Assessment Scale‐Cognitive (ADAS‐Cog11) and (2) 18‐month change in CenTauR‐Meta‐temporal SUVr.ResultsCenTauR‐Universal and CenTauR‐Meta‐Temporal derived T+ groups showed comparable SNRs (Figure 1A‐B) and agreement with amyloid positivity (Figure 2). The TauVQ‐ and the visual read‐derived T+ groups also performed similarly. The regional early tau VOI‐based T+ group, compared to the global AD‐signature neocortical‐based T+ group, showed a higher SNR for 18‐month change in CenTauR‐Meta‐temporal SUVr. However, a lower SNR for annualized ADAS‐Cog11 change and a lesser agreement with amyloid positivity were observed. Comparisons using PET‐to‐autopsy cohort will be presented.ConclusionsOur analyses suggest using CenTauR‐Meta‐temporal and visual read‐based regional T+ criteria may identify a larger subgroup of symptomatic patients exhibiting similar amyloid positivity prevalence and clinical decline compared to those determined by corresponding global T+ criteria. Among examined methods, the early tau VOI‐based T+ criterion possibly captures the earliest pathologic stage. Lastly, CenTauR‐based T+ groups showed lower SNRs for tau and clinical progression, suggesting flortaucipir‐specific criteria might be more sensitive for prognostic evaluations. Further validations using different datasets and cut points are warranted.

Factors Associated with Myocardial Uptake on Oncologic Somatostatin PET Investigations and Differentiation from Myocardial Uptake of Acute Myocarditis.

Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(β), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(β), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.

18F]FDG-PET/CT atypical response patterns to immunotherapy in non-small cell lung cancer patients: long term prognosis assessment and clinical management proposal.

To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). 109 patients were prospectively included and underwent [18F]FDG-PET/CT at baseline, after 7 weeks (PETinterim1), and 3 months (PETinterim2) of treatment. On PETinterim1, tumor response was assessed using standard PERCIST criteria. In the event of PERCIST progression at this time-point, the study design provided for continued immunotherapy for 6 more weeks. Additional response patterns were then considered on PETinterim2: pseudo-progression (PsPD, subsequent metabolic response); dissociated response (DR, coexistence of responding and non-responding lesions), and confirmed progressive metabolic disease (cPMD, subsequent homogeneous progression of lesions). Patients were followed up for at least 12 months. Median follow-up was 21 months. At PETinterim1, PERCIST progression was observed in 60% (66/109) of patients and ICPI was continued in 59/66. At the subsequent PETinterim2, 14% of patients showed PsPD, 11% DR, 35% cPMD, and 28% had a sustained metabolic response. Median overall survival (OS) and progression-free-survival (PFS) did not differ between PsPD and DR (27 vs 29 months, p = 1.0; 17 vs 12 months, p = 0.2, respectively). The OS and PFS of PsPD/DR patients were significantly better than those with cPMD (29 vs 9 months, p < 0.02; 16 vs 2 months, p < 0.001), but worse than those with sustained metabolic response (p < 0.001). This 3-group prognostic stratification enabled better identification of true progressors, outperforming the prognostic value of standard PERCIST criteria (p = 0.03). [18F]FDG-PET/CT enables early assessment of response to immunotherapy. The new wsPERCIST ("wait and see") PET criteria proposed, comprising immune-related atypical response patterns, can refine conventional prognostic stratification based on PERCIST criteria. HDH F20230309081206. Registered 20 April 2023. Retrospectively registered.

Combined modality for localized gastric diffuse large B-cell lymphoma: Long-term outcomes of 50 patients.

7079 Background: R-CHOP is the primary treatment for gastric diffuse large B-cell lymphoma (GDLBCL); for localized disease, the role of consolidative radiation therapy (RT) after chemotherapy remains underexplored. This study focuses on localized GDLBCL undergoing a combined modality therapy of R-CHOP followed by gastric RT, comparing outcomes between those receiving short-course (3-4 cycles) and full-course (6 cycles) R-CHOP. Methods: A retrospective analysis identified 50 consecutive PGDLBCL pts treated with R-CHOP followed by RT between 1/2000-1/2021. Baseline characteristics and follow-up data were collected. Lugano PET criteria and endoscopy (EGD) assessed overall response rate. Kaplan-Meier and univariable cox regression models estimated overall survival (OS) and (PFS). Results: Of the 50 pts with localized (Stage I-II) disease, 34 (68%) received 3-4 cycles of R-CHOP and 16 (32%) received 6 cycles. Pre-RT disease evaluation varied, with 36 (72%) undergoing EGD and PET, 4 (8%) EGD and CT, and 6 (12%) PET alone. One pt (3%) exhibited active DLBCL post 3-4 cycle R-CHOP, while 5 (31%) did so after 6 cycles (p=0.1). Median time from last R-CHOP dose to RT start date was 1.2 months with a median 3060 cGy delivered dose for both groups (range 2340-3060 in the 3-4 cycle group, 3000-4500 in the 6-cycle group). Median follow-up time from RT end is 58 months. No in-field failures occurred post-complete response (CR); however, 1 pt did not achieve a CR following R-CHOP and RT, progressing in the stomach and subsequently at new, out-of-field (OOF) sites. 3 pts had OOF progression without relapses in the stomach in a median time of 21 months. Low-grade lymphoma in the stomach post-DLBCL CR was observed in 2 pts, 3 and 22 months from RT end, with 1 OOF marginal zone lymphoma 2 years-post RT. OS and PFS did not significantly differ between the 3-4 and 6 cycle groups (96-month OS 70% vs. 86%, p=0.8; 96-month PFS 76% vs. 86%, p=0.7). OS and DLBCL PFS were analyzed for pts with evidence of residual DLBCL pre-RT compared to those without evidence of disease after R-CHOP. The 24-month DLBCL PFS was 92% in the CR group and 67% for those with incomplete response (p=0.14), with 92% and 67% 24-month survival probability (p=0.11). On univariate analysis, pre-RT evidence of active DLBCL by PET and/or EGD, pre-RT PET FDG uptake, and achieving CR on first-post-RT imaging were not statistically significant for DLBCL PFS. Conclusions: Recognizing the limitations of a retrospective study, our study documents the effectiveness of short-course R-CHOP followed by RT in localized GDLBCL, with similar outcomes to the full 6-cycle regimen. Excellent disease control was observed, with few instances of DLBCL or low-grade lymphoma relapse. Further analysis will include a cohort receiving R-CHOP alone without consolidative RT. This analysis aims to contribute to the evolving standard of care for GDLBCL, providing insights for future treatment strategies.

68Ga-Fibroblast Activation Protein Inhibitor PET/CT Improves Detection of Intermediate and Low-Grade Sarcomas and Identifies Candidates for Radiopharmaceutical Therapy.

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of 68Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of 68Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent 68Ga-FAPI PET/CT and 18F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUVmax) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of 68Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of 68Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUVmax greater than 10 for all tumor regions. Results: 68Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUVmax ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of 68Ga-FAPI versus 18F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of 68Ga-FAPI was higher than that of 18F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). 68Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, 68Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18F-FDG PET. 68Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.

Reactive axillary lymph nodes after COVID-19 mRNA vaccination: comparison of mRNA vs. attenuated whole-virus vaccines.

To compare the incidence and natural course of reactive axillary lymph nodes (RAL) between mRNA and attenuated whole-virus vaccines using Deauville criteria. In this multi-institutional PET-CT study comprising multiple vaccine types (Pfizer-BioNTech/Comirnaty, Moderna/Spikevax, Sinovac/CoronaVac and Janssen vaccines), we evaluated the incidence and natural course of RAL in a large cohort of oncological patients utilizing a standardized Deauville scaling system (n=522; 293 Female, Deauville 3-5 positive for RAL). Univariate and multivariate analyses were conducted to evaluate the predictive value of clinical parameters (absolute neutrophil count [ANC], platelets, age, sex, tumor type, and vaccine-to-PET interval) for PET positivity. Pfizer-BioNTech/Comirnaty and Moderna vaccines revealed similar RAL incidences for the first 20 days after the second dose of vaccine administration (44% for the first 10 days for both groups, 26% vs. 20% for 10-20 days, respectively for Moderna and Pfizer). However, Moderna recipients revealed significantly higher incidences of RAL after 20 days compared to Pfizer-BioNTech/Comirnaty, with nodal reactivity spanning up to the 9th week post-vaccination (15% vs. 4%, respectively P < 0.001). No RAL was observed in patients who received either a single dose of J&J vaccine or two doses of CroronaVac. Younger patients showed increased likelihood of RAL, otherwise, clinical/demographic parameters were not predictive of RAL ( P = 0.014 for age, P > 0.05 for additional clinical/demographic parameters). RAL based on strict PET criteria was observed with mRNA but not with attenuated whole-virus vaccines, in line with higher immunogenicity and stronger protection offered by mRNA vaccines.

Intra-arterial PRRT with Lu-177 DOTATATE in Liver-dominant Metastatic Neuroendocrine Tumors: Early Assessment of Efficacy and Toxicity.

We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Background/Objectives: Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Materials/Methods: 285 consecutive pts with PG lymphomas treated with RT between 1/2000-1/2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE v4.0. Results: Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 years (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-year OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Conclusion: Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

Very Low Dose Radiation Therapy for Indolent Lymphomas: Comparing “Big Boom” (4 Gy x 1) vs. “Boom Boom” (2 Gy x 2)

Indolent lymphomas are exquisitely sensitive to radiation therapy (RT). Programs of 2 Gy x 2 were shown to be highly effective in controlling irradiated site(s). During the COVID-19 pandemic, the International Lymphoma Radiation Oncology Group (ILROG) proposed guidelines that offered substitution of the Boom Boom (BB) (2 Gy x 2) regimen with Big Boom (Big B) of 4 Gy x 1. This report compares our center's experience with both regimens. We included patients with indolent lymphomas in this retrospective single institution study. After April 2020 both options of very low dose and choice of a standard full dose of 24 Gy were discussed with the patient. Patients were treated with a definitive or palliative intent depending on disease stage and prior therapy exposure. Patients treated with 24 Gy are not included in this report. Toxicity was reported as per CTCAE v4.0. Overall response rate (ORR) was assessed with Lugano PET criteria at the initial post-RT imaging. Differences between the two groups were examined using the Fisher's exact test and Mann-Whitney test. We evaluated a total of 471 lesions in 386 patients, including 172 lesions (37%) treated with 4 Gy x 1 and 299 lesions (63%) treated with 2 Gy x 2. Table 1 summarizes the patient and treatment characteristics. Age at the time of RT and sex were not significantly different between the two groups. The BB cohort was more likely to have follicular lymphomas (FL) (66% vs 54%, p = 0.011), though the proportion of higher-grade FL was similar between cohorts. The ORR was similar (Big B = 86%, BB = 87%) at the first post-RT evaluation (median of 2.23 months from RT for both cohorts). There was no significant difference in the rate of complete response, partial response, stable disease, or progressive disease between the cohorts at initial post-RT imaging. For both regimens, no directly related short-term side effects were observed. Both the 4 Gyx1 and 2 Gyx2 regimens demonstrated excellent ORR at the initial post-RT imaging assessment among patients with indolent lymphomas. While longer term follow-up is required to confirm durability of these findings, our initial experience suggests that 4 Gyx1 regimen recommended by ILROG during the pandemic is an effective treatment approach.

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Two hundred eighty-five consecutive pts with PG lymphomas treated with RT between January 2000 and January 2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE version 4.0. Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 yrs (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-yr OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

Prevalence of intra-patient inter-metastatic heterogeneity in mCRPC patients based on triple-tracer PET imaging: The 3TMPO study.

5033 Background: Intra-patient inter-metastatic heterogeneity (IIH) has been demonstrated in metastatic castration resistant prostate cancer (mCRPC) patients based on genomic and imaging studies, most often after several lines of therapies. IIH is of utmost importance for PSMA radioligand therapy (RLT) eligibility, biopsy-based precision medicine and/or treatment intensification decision-making. The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study (NCT04000776) is a prospective multicenter PET imaging study that was designed to determine the prevalence of IIH in mCRPC patients and to determine candidacy for RLT. Methods: 3TMPO is a PET-imaging trial including mCRPC patients showing at least 3 metastases on conventional imaging with evidence of biochemical or radiographic progression, at least 3 months after initiation of the last systemic therapy. 68Ga-PSMA-617 and 18F-FDG PET/CT scans were performed within 10 days and analyzed quantitatively. A third scan with 68Ga-Octreotate was done when a PSMA-/FDG+ lesion was found. For all tracers, positivity of a lesion was defined as its SUVpeak being 1.5 times higher than the SUVmean of the liver. Lesions smaller than 1 cc and likely benign foci of uptake were excluded. IIH prevalence was the primary outcome, defined as the percentage of patients having at least two lesions with discordant features on PET imaging. Results: We included 98 patients in the final analysis. Patients had a mean age of 69 years and a median PSA of 51.1 ng/mL. Number of metastases were &lt;5 in 46.9% and ≥10 in 33.7% of patients and 10.2, 20.4, 18.4 and 51.0% had received 0, 1, 2 or &gt;2 lines of systemic therapies for mCRPC, respectively. Prevalence of IIH was 83.7% based on pre-specified PET criteria. Overall, seven different combinations of lesion phenotypes were found among patients based on FDG and PSMA PETs, and at least one PSMA-/FDG+ lesion was found in 46 patients (46.9%). Of the 44 patients who underwent Octreotate PET, six (13.6%) had at least one Octreotate-positive lesion. In this FDG/PSMA/Octreotate-imaged subgroup, 11 different combinations of phenotypes were observed between metastases of individual patients. Overall, 52.0% (IC95: 41.7-62.2) of patients were found to be candidate for PSMA RLT, but none for Octreotate RLT. Conclusions: The majority of mCRPC patients showed IIH. Based on a multi-tracer approach, up to 11 lesion phenotype combinations were found amongst patients. Correlation of these imaging phenotypes with genomics and treatment response will be highly relevant for optimized precision medicine, especially with respect to PSMA-RLT. Clinical trial information: NCT04000776 . [Table: see text]

VERY LOW DOSE RADIATION THERAPY FOR INDOLENT LYMPHOMA: COMPARING “BIG BOOM” (4GY × 1) VERSUS “BOOM BOOM” (2GY × 2)

Purpose/Objectives: Indolent lymphomas are exquisitely sensitive to radiation therapy (RT). Programs of 2Gy × 2 were shown to be highly effective in controlling irradiated site(s). During the COVID-19 pandemic, the International Lymphoma Radiation Oncology Group (ILROG) proposed guidelines that offered substitution of the Boom Boom (2Gy × 2) regimen with Big Boom of 4Gy × 1. This report compares our center’s experience with both regimens. Materials/Methods: We included patients with indolent lymphomas in this retrospective single institution study. After April 2020, both options of very low dose and choice of a standard full dose of 24Gy were discussed with the patients. Patients were treated with a definitive or palliative intent depending on disease stage and prior therapy exposure. Patients treated with 24Gy are not included in this report. Overall response rate (ORR) was assessed with Lugano PET criteria at the initial post-RT imaging. Differences between the two groups were examined using the Fisher’s exact test and Mann-Whitney test. Results: We evaluated a total of 471 lesions in 386 patients, including 172 lesions (37%) treated with 4Gy × 1 and 299 lesions (63%) treated with 2Gy × 2. Table 1 summarizes the patient and treatment characteristics. Age at the time of RT and sex were not significantly different between the two groups. The 2Gy × 2 cohort was more likely to have follicular lymphomas (FL) (66% vs. 54%, p = 0.011), though the proportion of higher-grade FL was similar between cohorts. The ORR was similar (4Gy × 1 = 86%, 2Gy × 2 = 87%) at the first post-RT evaluation (median of 2 months from RT for both cohorts). There was no significant difference in the rate of complete response, partial response, stable disease, or progressive disease between the cohorts at initial post-RT imaging. For both regimens, no directly related short-term side effects were observed. Conclusions: Both the 4Gy × 1 and 2Gy × 2 regimens demonstrated excellent ORR at the initial post-RT imaging assessment among patients with indolent lymphomas. While longer term follow-up is required to confirm durability of these findings, our initial experience suggests that 4Gyx1 regimen recommended by ILROG during the pandemic is an effective treatment approach. FL Grade 3A FL Grade 3B FL Grade 1-2 7 (4.1%) 0 86 (50%) 7 (2.3%) 2 (0.7%) 188 (63%) >5 cm ≤5 cm Unknown 15 (8.7%) 96 (56%) 61 (35%) 40 (13%) 259 (87%) 0 Complete Response Partial Response Progressive Disease Stable Disease Not assessed yet 93 (62%) 35 (23%) 6 (4%) 15 (10%) 23 190 (64%) 68 (23%) 16 (5.4%) 24 (8.1%) 1 Keywords: indolent non-Hodgkin lymphoma, radiation therapy No conflicts of interests pertinent to the abstract.

Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast.

Background: Metastatic breast cancer is associated with a poor prognosis and therefore, innovative therapies are urgently needed. Here, we report on the results of a Phase I-II study using DeltaRex-G for chemotherapy resistant metastatic carcinoma of breast. Patients and Methods: Endpoints: Dose limiting toxicity; Antitumor activity. Eligibility: ≥18years of age, pathologic diagnosis of breast carcinoma, adequate hematologic and organ function. Treatment: Dose escalation of DeltaRex-G 1-4 x 1011cfu intravenously thrice weekly x 4 weeks with 2-week rest period. Treatment cycles repeated if there is ≤ Grade 1 toxicity until disease progression or unacceptable toxicity. Safety: NCI CTCAE v3 for adverse events reporting, vector related testing. Efficacy: RECIST v1.0, International PET criteria and Choi criteria for response, progression free and overall survival. Results: Twenty patients received escalating doses of DeltaRex-G from 1 × 1011cfu to 4 × 1011cfu thrice weekly for 4weeks with a 2-week rest period. Safety: ≥ Grade 3 treatment-related adverse event: pruritic rash (n = 1), no dose limiting toxicity, no replication-competent retrovirus, nor vector-neutralizing antibodies detected. No vector DNA integration was observed in peripheral blood lymphocytes evaluated. Efficacy: by RECIST v1.0: 13 stable disease, 4 progressive disease; tumor control rate 76%; by PET and Choi Criteria: 3 partial responses, 11 stable disease, 3 progressive disease; tumor control rate 82%. Combined median progression free survival by RECIST v1.0, 3.0months; combined median overall survival, 20months; 1-year overall survival rate 83% for Dose Level IV. Biopsy of residual tumor in a participant showed abundant CD8+ killer T-cells and CD45+ macrophages suggesting an innate immune response. Two patients with pure bone metastases had >12-month progression free survival and overall survival and are alive 12years from the start of DeltaRex-G therapy. These patients further received DeltaRex-G + DeltaVax for 6months. Conclusion: Taken together, these data indicate that 1) DeltaRex-G has a distinctively high level of safety and exhibits anti-cancer activity, 2) PET/Choi provide a higher level of sensitivity in detecting early signs of tumor response to DeltaRex-G, 3) DeltaRex-G induced 12- year survival in 2 patients with pure bone metastases who subsequently received DeltaVax immunotherapy, and 4) DeltaRex-G may prove to be a biochemical and/or immune modulator when combined with other cancer therapy/immunotherapy.

68Ga-Pentixafor PET/MRI for Treatment Response Assessment in Mantle Cell Lymphoma: Comparison Between Changes in Lesion CXCR4 Expression on PET and Lesion Size and Diffusivity on MRI.

The aim of this study was to compare CXCR4 imaging with 68Ga-pentixafor PET to MRI for treatment response assessment in patients with mantle cell lymphoma (MCL). Twenty-two posttreatment 68Ga-pentixafor PET/MRI scans of 16 patients (7 women and 9 men; mean age, 69.9 ± 7.9) with a total of 67 target lesions on baseline PET/MRI were analyzed. Rates of complete remission per lesion and per scan, according to MRI (based on lesion size) and 68Ga-pentixafor PET (based on SUV decrease to lower than liver and blood pool uptake), were compared using McNemar tests. The t tests and Pearson correlation coefficients (r) were used to compare rates of change in lesion diameter products (DPs) on MRI, and standardized uptake values (SUVmax, SUVmean) on PET, relative to baseline. At interim PET/MRI, 18/32 (56.3%) target lesions met CR criteria on 68Ga-pentixafor PET, and 16/32 (50.0%) lesions met size-based MRI criteria for CR (P = 0.63). At end-of-treatment PET/MRI, 40/57 (70.2%) target lesions met 68Ga-pentixafor PET criteria for CR, and 27/57 (47.4%) lesions met size-based MRI criteria for CR (P = 0.021). Complete remission after treatment was observed more frequently on 68Ga-pentixafor PET (11/22 scans, 54.5%) than on MRI (6/22 scans, 27.3%) (P = 0.031). Rates of change did not differ significantly between lesion DP (-69.20% ± 34.62%) and SUVmax (-64.59% ± 50.78%, P = 0.22), or DP and SUVmean (-60.15 ± 64.58, P = 0.064). Correlations were strong between DP and SUVmax (r = 0.71, P < 0.001) and DP and SUVmean (r = 0.73, P < 0.001). In MCL patients, 68Ga-pentixafor PET may be superior for assessment of complete remission status than anatomic MRI using lesion size criteria, especially at the end of treatment.

Abstract P5-01-11: Utility of 18F-FDG PET/CT for the prediction of pathologic complete response in axilla to neoadjuvant chemotherapy in breast cancer

Abstract Purpose: To evaluate the value of early FDG-PET (18F-Fluorodeoxyglucose-Positron Emission Tomography) metabolic criteria for prediction of pathologic complete response in axilla (pCRAx) after neoadjuvant chemotherapy (NAC) in breast cancer. Methods: Inclusion criteria were all T-stage breast cancers, non-metastatic, with initial lymph node involvement estimated by PET +/- lymph node biopsy, treated with NAC followed by surgery with axillary lymph node dissection (ALND), managed at the George-François Leclerc Cancer Center in Dijon, France, between 2009 and 2019. A PET was performed before and after the first course of chemotherapy (PET1 and PET2). pCRAx was defined as the absence of invasive cells in the nodes at the time of ALND (i.e. ypN0). The Sataloff classification was used as reference on each pathological report. Patients with a Sataloff NA classification (i.e. evidence of therapeutic effect, and no residual disease) and, if axillary involvement was proven at diagnosis, NB (i.e. no metastasis, no therapeutic effect) were considered as pCRAx. The PET metabolic criteria studied in the axilla were: - SUVmax (Standard Uptake Value) on PET1 and PET2 = fixation in the axillary voxel with the highest activity (kBq/mL)/(injected dose (kBq)/weight (g)) - ΔSUVmax (%) = metabolic response after the first course of NAC = 100 x (SUVmax1 - SUVmax2)/(SUVmax1). Univariate and multivariate analysis were performed to identify factors (clinical, pathologic, metabolic) that may be associated with pCRAx. Relationships between baseline TEP uptake and prognostic parameters were assessed using Receiver Operating Characteristic (ROC) curves. Results: Among 188 patients included, the rate of pathologically proven node involvement was 63.3% (n=119). The pCRAx rate was 45.7% (n=86/188) but varied according to tumor subtypes: 14.5% (n=9/62) of HR(Hormone Receptor)+/HER2-negative, 47.7% (n=21/44) of HR+/HER2-positive, 61.4% (n=27/44) of triple-negative (TN) and 76.3% (n=29/38) of HR-/HER2-positive. Factors significantly associated with pCRAx were by univariate analysis: HER2-positive (HR+ and HR-) and TN subtypes (p&amp;lt; 0.001), SBR (Scarff-Bloom-Richardson) grade (p=0.01), breast pCR (ypT0/is) (p&amp;lt; 0.001), SUVmax2 (p=0.01) and ΔSUVmax (p&amp;lt; 0.001). By multivariate analysis, it persisted the HR-/HER2-positive (p=0.02) and TN (p=0.02) subtypes and breast pCR (p&amp;lt; 0.001). In global population, a decrease in ΔSUVmax of 63% was the optimal threshold to predict pCRAx (Area Under the Curve AUC = 0.73) with a sensitivity (Se) of 51% and specificity (Sp) of 83%. ΔSUVmax remains the best performing parameter in TN (AUC = 0.72; Se at 52%; Sp at 88%). In HR-/HER2-positive patients, SUVmax2 appeared to be a better predictor of pCRAx than ΔSUVmax. A SUVmax2 value of 1.99 was the optimal threshold for predicting pCRAx (AUC = 0.72), yielding a Se of 66% and a Sp of 78%. None of the PET criteria predicted axillary response with sufficient accuracy for HR+ subtypes. Conclusion: PET alone does not appear to be sufficient to predict pCRAx. It seems necessary to use other parameters, whether clinical, biological or imaging, to discriminate responders from non-responders to NAC in order to adapt the subsequent surgical management. Citation Format: ELOISE MICHEL, FRANCOISE BELTJENS, ALEXANDRE COCHET, JEAN LOUIS ALBERINI, CHARLES COUTANT, CLEMENTINE JANKOWSKI. Utility of 18F-FDG PET/CT for the prediction of pathologic complete response in axilla to neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-11.

Is 18F-FDG PET Needed to Assess 177Lu-PSMA Therapy Eligibility? A VISION-like, Single-Center Analysis.

18F-FDG and prostate-specific membrane antigen (PSMA) PET have been used to assess eligibility for PSMA-targeted therapy by some centers. However, it remains unclear whether both examinations are needed as a part of workup in the clinical practice or whether PSMA PET alone, as was done in the positive phase 3 VISION trial, is sufficient to identify suitable candidates. The aim was to reanalyze all patients who underwent both 18F-FDG and PSMA PET for PSMA-targeted therapy eligibility assessment using the VISION trial criteria. Methods: Eighty-nine men with metastatic castration-resistant prostate cancer referred to 177Lu-PSMA therapy from June 2019 to October 2021 who underwent both 18F-FDG and PSMA PET (using either 68Ga-PSMA-11 or 18F-PSMA-1007) examinations within 2 wk were included in this analysis. Eligibility status was determined in accordance with either knowledge of both 18F-FDG and PSMA PET (clinical routine) or VISION criteria with PSMA PET-only (study reassessment, done twice with liver only for PSMA-11 and liver/spleen as reference for PSMA-1007). A metastasis seen on 18F-FDG PET or CT but not on PSMA PET was denoted as a mismatch finding and led to exclusion from 177Lu-PSMA therapy. On the basis of clinical assessment, 52 patients received 177Lu-PSMA therapy, and 37 did not; all patients were reassessed. Results: Patients treated with 177Lu-PSMA therapy had significantly longer overall survival than those not treated (12.4 vs. 6.8 mo, P < 0.01). PSMA-only analysis (spleen/liver reference) and 18F-FDG/PSMA mismatch reads had substantial agreement (Cohen κ = 0.73). Eighteen percent (n = 16/89) of patients had a mismatch finding based on 18F-FDG/PSMA PET. With the liver/spleen reference, a minor fraction of patients who had no mismatch finding (and were therefore treated) would have been withheld from therapy by PSMA-only analysis (3%). Three percent (n = 3) of all patients had an 18F-FDG/PSMA mismatch finding not detected by PSMA PET-only (VISION-like) analysis. For patients not receiving PSMA therapy, the overall survival was not statistically significantly different comparing 18F-FDG/PSMA mismatch versus nonmismatch (P = 0.61) patients. Conclusion: 18F-FDG and PSMA PET provide complementary information, yet less than 5% of patients had mismatch findings not detected using PSMA PET-only. Based on our data, 18F-FDG/PSMA mismatch examination and PSMA-only analysis have a substantial level of agreement.

Determining the amyloid PET and CSF inclusion criteria for the SKYLINE secondary prevention study with gantenerumab

AbstractBackgroundSKYLINE is a secondary prevention study in Alzheimer's disease (AD) enrolling amyloid‐positive, cognitively normal (CN) individuals at risk for clinical AD between 60–80 years and treating them with gantenerumab or placebo for 4 years. There is no gold standard for determining amyloid positivity for this purpose. Thresholds for amyloid positivity used in trials in symptomatic AD may be suboptimal in a secondary prevention setting, where amyloid positivity prevalence is lower. We compared various amyloid‐positive definitions in a CN elderly population based on how well they enrich for clinical progression over 4 years and operational feasibility.MethodFour cohorts (ADNI, BioFINDER‐1, AIBL, and HABS) were used to explore the relationship between amyloid PET visual read, centiloid values and CSF pTau/Abeta42 values in a CN population. For amyloid PET, we compared visual read with centiloid thresholds by evaluating the amyloid positivity prevalence, magnitude and variability of endpoint progression, and positive and negative predictive value (PPV and NPV). Operational advantages of CSF motivated a comparison of elevated CSF pTau/Abeta42 thresholds with amyloid PET. We interrogated which CSF thresholds were robust to preanalytical differences, had a high PPV and NPV compared with amyloid PET, and resulted in an acceptable degree of cognitive decline and variability.ResultHigher centiloid thresholds (≥40 CL) showed good agreement with visual read, but visual read resulted in a lower coefficient of variation (CV) for change from baseline in PACC5, the primary endpoint in SKYLINE (CV=118–210 vs. CV=150–336). An elevated CSF pTau/Abeta42 threshold resulted in a similar amyloid positivity prevalence to amyloid PET (14–17% vs. 10–20%), had acceptable NPV (95–97%), PPV (69–87%), sensitivity (71–82%), and specificity (95–98%) for visual read, and resulted in a similar CV for change from baseline in PACC5.ConclusionThere is no gold standard for determining the optimal amyloid positivity threshold in a secondary prevention trial. Determining patients to be amyloid‐positive if they are amyloid PET visual read‐positive or have elevated CSF pTau/Abeta42 offers not only operational advantages but also likely results in a trial population that has an acceptable level of endpoint progression and variability over the trial duration.

"Big Boom" (4 Gy x 1) Radiation Treatment (RT) Versus "Big Boom" (2 Gy x 2) for Non-Hodgkin Lymphoma (NHL)

Purpose/Objectives Indolent lymphomas are exquisitely sensitive to radiation. Recently, programs of only 4 Gy in 2 daily fractions (Boom-Boom) were shown to be highly effective in controlling irradiated site(s). During the COVID-19 pandemic, the International Lymphoma Radiation Oncology Group (ILROG) proposed guidelines that allowed substitution of the Boom Boom (2 Gy x 2) regimen with Big Boom single fraction regimen of only 4 Gy. This report compares our center's experience with Big Boom to Boom-Boom. Materials/Methods All consecutive indolent lymphomas were included. After April 2020 both options of very low dose as well as choice of a standard full dose of 24 Gy were discussed with the patient and choice was made with consideration of access logistics, patient preference as well as disease site(s). Patients were treated with a definitive or palliative intent depending on disease stage and prior therapy exposure. Patients treated with 24 Gy are not included in this report. Overall response rate was assessed with Lugano PET criteria at the initial post-RT imaging. Differences between the two groups were examined using the Fisher's exact test and Mann-Whitney test. Results We evaluated a total of 440 lesions in 363 patients, including 142 lesions (32%) treated with 4 Gy x 1 ("Big Boom") and 298 lesions (67%) treated with 2 Gy x 2 ("Boom Boom"). Table 1 summarizes the patient and treatment characteristics. Patient age at the time of RT, sex, and the proportion of treated lesions with maximum axial diameter of greater than 5 cm were not significantly different between the two groups. Marginal zone lymphoma comprised 27% of each cohort. The Big Boom cohort was more likely to have follicular lymphomas (66% vs 52%, p = 0 .003), though the proportion of higher-grade follicular lymphomas was similar between cohorts. The overall response rate was 87% for both groups at the first post-RT evaluation (median of 2 months from RT for both cohorts). Furthermore, there was no significance difference in the rate of complete response, partial response, stable disease, or progressive disease between the cohorts at initial post-RT imaging. For both regimens, no directly related short-term side effects were observed. Conclusions Both the Big Boom and Boom Boom regimens demonstrated excellent overall response rates at the initial post-RT imaging assessment among patients with indolent lymphomas. While longer term follow-up is required to confirm durability of these findings, our initial experience suggests that the single dose, single visit Big Boom regimen (4 Gy x 1) recommended by ILROG during the Covid-19 pandemic is an effective treatment approach. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PET-directed combined modality therapy for gastroesophageal junction cancer: Results of the multicentre prospective MEMORI trial of the German Cancer Consortium (DKTK)

BackgroundPositron emission tomography (PET) may differentiate responding and non-responding tumours early in the treatment of locally advanced gastroesophageal junction adenocarcinomas. Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). MethodsPatients underwent baseline 18F-FDG PET followed by 1 cycle of CTX. PET was repeated at day 14–21 and responders (P-R), defined as ≥35% decrease in SUVmean from baseline, continued with CTX. P-NR switched to CRT (CROSS). Patients underwent surgery 4–6 weeks post-CTX/CRT. The primary objective was an improvement in R0 resection rates in P-NR above a proportion of 70%. ResultsIn total, 160 patients with resectable gastroesophageal junction adenocarcinomas were prospectively investigated by PET scanning. Eighty-five patients (53%) were excluded. Seventy-five eligible patients were enrolled in the study. Based on PET criteria, 50 (67.6%)/24 (32.4%) were P-R and P-NR, respectively. Resection was performed on 46 responders, including one patient who withdrew the ICF, and 22 non-responders (per-protocol population). R0 resection rates were 95.6% (43/45) for P-R and 86.4% (19/22) for P-NR. No treatment related deaths occurred. With a median follow-up time of 24.5 months, estimated 18 months DFS was 75.4%/64.2% for P-R/P-NR, respectively. The estimated 18 months OS was 95.5% for P-R and 68.2% for P-NR. ConclusionThe primary endpoint of the study to increase the R0 resection rate in metabolic NR was not met. PET response after induction CTX is prognostic for outcome with a prolonged OS and DFS in PET responders. Trial registrationNCT 2014-000860-16.

Prognostic Potential of Postoperative 18F-Fluorocholine PET/CT in Patients With High-Grade Glioma. Clinical Validation of FuMeGA Postoperative PET Criteria.

The aim of this study was to assess the prognostic performance of postoperative 18F-fluorocholine PET/CT in patients with high-grade glioma (HGG). Patients with HGG who underwent preoperative and postoperative 18F-fluorocholine PET/CT were prospectively enrolled in the study. Postoperative MRI was classified as complete versus incomplete resection. Postoperative 18F-fluorocholine PET/CT was classified as negative (complete) or positive for metabolic residual tumor (incomplete resection) using a 5-point score system. The correlation of positive locations on PET/CT with the sites of subsequent tumor recurrence was evaluated. The concordance of postoperative imaging techniques (Cohen κ) and their relation with progression-free survival and overall survival were assessed using Kaplan-Meier method and Cox regression analysis. Fifty-one studies, belonging to 47 patients, were assessed. Four patients underwent 2 postoperative 18F-fluorocholine PET/CT scans as they needed a second tumor resection for recurrence. In the follow-up, 42 patients progressed, and 37 died. Concordance between postoperative PET/CT and MRI assessment was poor. Resection grade on MRI did not show any significant association with prognosis. In multivariate analysis, only age and postoperative PET/CT showed significant association with progression-free survival (hazard ratio [HR], 1.03 [1.01-1.06, P = 0.006] and 1.88 [0.96-3.71, P = 0.067], respectively) and overall survival (HR, 1.04 [1.01-1.07, P = 0.004] and 2.63 [1.22-5.68, P = 0.014], respectively). Postoperative positive 18F-fluorocholine PET/CT locations correlated with the sites of subsequent tumor recurrence in 81.82% of cases. Postoperative 18F-fluorocholine PET/CT seems superior to postoperative MRI in the outcome prediction of patients with HGG, outperforming it in the identification of the most probable location of tumor recurrence.