Median SUV Research Articles

Maximum standardized uptake value-to-tumor size ratio in fluorodeoxyglucose F18 positron emission tomography/computed tomography: a simple prognostic parameter for non-small cell lung cancer.

By correcting the effect of tumor size on metabolic activity, the maximum standardized uptake value-to-tumor size (SUVmax:tumor size) ratio on fluorodeoxyglucose F18 positron emission tomography (18F-FDG PET)/computed tomography (CT) scans can be a prognostic parameter of non-small cell lung cancer (NSCLC). The current study evaluates the prognostic value of SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans in patients with NSCLC. Furthermore, the SUVmax:tumor size ratio is compared with other established PET parameters. This study included 108 patients with NSCLC who underwent pretreatment 18F-FDG PET/CT scans and curative lung surgery. The associations between the SUVmax:tumor size ratio and other conventional PET parameters were investigated. The recurrence-free survival according to the SUVmax:tumor size ratio was also analyzed. In addition, the SUVmax:tumor size ratio was compared according to postoperative pathologic findings. In total, 72 (66.7%) of the 108 participants presented with adenocarcinoma (ADC). Nineteen (17.6%) patients experienced recurrence during a median follow-up period of 32.3 months. The median SUV max:tumor size ratio was 2.37 (1.23 for ADCs and 3.90 for other histologic types). The SUVmax:tumor size ratio was associated with SUVmax and mean SUV, as well as metabolic tumor volume and total lesion glycolysis. Patients with an SUVmax:tumor size ratio higher than the median had a worse recurrence outcome than those with an SUVmax:tumor size ratio lower than the median. Participants with ADC who presented with lymphovascular invasion had a higher SUVmax:tumor size ratio than those without. The presence of lymph node metastasis and advanced histologic grade were associated with a high SUVmax:tumor size ratio in patients with ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans was associated with aggressive tumor behavior and poor outcome in NSCLCs, particularly ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans has a prognostic value in patients with NSCLCs, especially ADC.

Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers.

Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.

Comparison of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in Fumarate Hydratase-Deficient Renal Cell Carcinoma : A Prospective and Single-Center Study.

Fumarate hydratase-deficient renal cell cancer (FHRCC) is a rare and aggressive form of renal cell carcinoma. The diagnostic value of 68 Ga-FAPI PET/CT for FHRCC remains unexplored. Therefore, we compared the potential value of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in FHRCC. Patients with FHRCC underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT from May 2022 to December 2023. The SUV max and tumor-to-liver ratio (TLR) of both tracers were compared using the Wilcoxon signed rank test. Eleven patients with 83 lesions were enrolled. The rate of 18 F-FDG PET/CT in detecting lesions was higher than that of 68 Ga-FAPI-04 PET/CT: primary tumors: 75.0% (6/8) versus 50.0% (4/8); lymph nodes: 94.9% (37/39) versus 89.7% (35/39); and bone lesions: 100.0% (21/21) versus 90.5% (19/21). The median SUV max of primary and metastatic lesions on 18 F-FDG PET/CT was comparable to 68 Ga-FAPI-04 PET/CT in semiquantitative analysis (primary lesions: 13.86 vs 16.35, P = 1.000; lymph nodes: 10.04 vs 9.33, P = 0.517; bone lesions: 13.49 vs 9.84, P = 0.107; visceral lesions: 8.54 vs 4.20, P = 0.056). However, the median TLRs of primary and metastatic lesions on 68 Ga-FAPI-04 PET/CT were higher than that of 18 F-FDG PET/CT (primary lesions: 30.44 vs 5.41, P = 0.010; lymph nodes: 17.71 vs 3.95, P = 0.000; bone lesions: 15.94 vs 5.21, P = 0.000; visceral lesions: 9.26 vs 3.44, P = 0.003). 18 F-FDG PET/CT detected more primary and metastatic FHRCC lesions than 68 Ga-FAPI-04 PET/CT. However, the higher TLR in FHRCC on 68 Ga-FAPI-04 PET/CT may indicate therapeutic potential in targeting fibroblast activation protein in FHRCC.

Pilot Feasibility Study: 18 F-DPA-714 PET/CT Macrophage Imaging in Triple-Negative Breast Cancers (EITHICS).

Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted. The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as "above muscular," "equal to muscular," and "below muscular" with reference to the muscular background. For the "above muscular" group (2 HAB and 2 MAB), "equal muscular" group (3 HAB, 3 MAB, and 1 LAB), and "below muscular" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02). This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.

Genomic Correlates of Radiosensitivity in Diffuse Large B Cell Lymphoma

Introduction Radiotherapy (RT) is beneficial for select patients with localized diffuse large B cell lymphoma (DLBCL), in both the early stage and relapsed/refractory settings. Although molecular subtyping plays a key role in classification of DLBCL, genomic predictors of local response to RT have yet to be adequately explored. To our knowledge, there are no existing studies investigating the genomic landscape of DLBCL patients treated with RT. Therefore, we sought to identify genomic signatures of radiosensitivity in localized DLBCL patients. Methods We analyzed an institutional database of DLBCL patients treated with RT for localized measurable disease treated between 2007-2022. All patients underwent next-generation sequencing using an institutional 505-gene panel (MSK-Impact). Clinical and radiographic characteristics were obtained from chart and imaging review. All patients had measurable disease on CT scan at time of RT and included both Ann Arbor stage I/II patients referred for consolidative radiotherapy and those with isolated sites of relapsed/refractory disease. Patients did not receive any systemic therapy between RT start and time of response assessment. The public NCI LymphGen algorithm was used to further classify genomic subgroups. Using Fisher's exact test and logistic regression, we tested for univariable correlation between specific gene alterations and LymphGen subgroups with initial radiation response, defined by Lugano criteria and decrease in maximum SUV. Results We identified 46 patients including 15 (33%) tumors treated in the early-stage setting (13% definitively without prior chemotherapy, 87% as consolidation), while 31 (60%) were treated in the localized relapsed/refractory setting. The majority were GCB subtype (57%) while 28% were non-GCB and 15% had missing immunohistochemistry data. The median number of prior lines of systemic therapy was 1 (0-2) in early stage and 1 (1-7) in localized relapsed/refractory diseases. The median RT dose was 36 Gy (4-54), with 38 (83%) tumors receiving at least 30Gy. The median lesion SUV at the time of RT was 4.11 (1.1-46.0). Complete response (CR) was achieved in 41% of tumors at the time of first imaging assessment (median 3.1 months) with a median of 90.3% (42-100%) decrease in SUV. The most commonly altered individual genes were KMT2D (35%), MYD88 (28%), and TP53 (35%). LymphGen classified 22% of cases as EZB subtype, 13% as MCD, 2% as BN2, 2% as ST2, and the remaining 61% were unclassified. Mutations in ETV6 (13% of tumors) were associated with a higher CR rate in response to RT (83% mutated vs 35% wildtype, p=0.068). Lesions from ETV6 mutated cases had similar SUVs (p=0.74) and sizes (p=0.92) as wildtype cases. Alterations in genes from the LymphGen MCD subgroup were associated with greater reductions in SUV (ETV6 p<0.0001, PIM1 p<0.0001, MYD88 p<0.001, and TNFAIP3 p=0.02) The MCD subgroup trended towards increased odds of CR post-RT (log odds 1.9, p=0.08) and greater reduction of SUV (p=0.07) compared to the EZB subgroup. Conclusions To our knowledge this is the first study evaluating the role of LymphGen subgrouping on radiotherapy response, and the first study to examine genomic alterations in DLBCL patients treated with radiation. Genomic biomarkers of radiosensitivity are needed to identify radioresponsive tumors which may benefit from better integration of RT into existing salvage paradigms such as CAR T cells. Our data suggest that alterations in MCD LymphGen subgroup genes (ETV6, PIM1, MYD88, TNFAIP3) may be associated with better response to radiotherapy. ETV6 is a strong hematopoietic transcription factor known to be altered in many human leukemias and myelodysplastic syndromes. Its role in DLBCL is not well defined, with preclinical studies suggesting a distinct role compared to leukemias. Due to the limited sample size, these findings are hypothesis generating and warrant further study with larger, prospective cohorts to validate the ability of genomic signatures to predict RT response.

CART-AI-Radiomics: Survival and Neurotoxicity Prediction in B-Cell Lymphoma Patients Treated with CAR-T Cells through an Imaging Features-Based Model

Background: Despite clinical outcome improvements observed in relapsed/refractory (R/R) B-cell lymphoma patients (pts) treated with antigen receptor modified T-cells (CAR-T cells), a sizeable proportion still progress or relapse after infusion. Besides, this procedure is associated with significant morbidity primarily due to the immune effector cell-associated neurotoxicity syndrome (ICANS). The main goal of the CART-AI-Radiomics study is to apply artificial intelligence to develop new imaging-based prognostic and predictive models that integrate molecular and imaging biomarkers towards improved stratification of pts at high risk of R/R. In this sub-study, we retrospectively assessed the ability of imaging features and clinical data to predict survival and neurotoxicity. Methods: Consecutive pts diagnosed of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) treated with anti-CD19 CAR-T cells from 2019-2022 in Valencia Clinic Hospital and La Fe Hospital were included (cut-off date: July 2023). All the pre-infusion flourine18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) scans and clinical data were collected. The volume of interest (VOI) was manually contoured for all visible lesions in the PET/CT imaging exams. A subsequent imaging features extraction was performed. Features included PET conventional parameters-maximum standardized uptake value (SUV max), metabolic tumor volume (MTV; defined as the volume of voxels with SUVs higher than the threshold of 41% × SUV max) and total lesion glycolysis (TLG)-and radiomic features. Imaging parameters were calculated for all lesions (total) and for the dominant lesion (DL), whereas clinical variables were measured before lymphodepletion (LD). Univariate and multivariate analyses were carried out using Cox proportional-hazards models for survival prediction and logistic regression for neurotoxicity assessment. Survival analyses were conducted according to MTV total values. Results: A total of 29 pts (median age 63.2 [range 21.8-79.3] years; 18 [62.1%] females) who received CAR-T cell therapy were included. Twenty-six (89.7%) pts had DLBCL and 3 (10.3%) had PMBCL. At the time of pre-LD, 22 (75.9%) pts had increased lactate dehydrogenase (LDH) levels 18 (62.1%), presented with stage IV disease, 16 (55.17%) with an International Prognostic Index (IPI) score of 3-5, 8 (27.6%) had bulky disease. Median number of prior treatment lines was 2 (range 2-6). Twenty-three (79.3%) pts were treated with axicabtagene ciloleucel and 6 (20.7%) with tisagenlecleucel. Bridging therapy before LD was required by 26 (89.6%) pts. For survival analyses, a cut-off MTV total value of 236.03 mL that maximized the Log-Rank statistic was selected to divide pts into high MTV total and low MTV total categories. Median overall survival (OS) was 5.7 [3.2-NA, 95% CI] months and 36.2 [13.9-NA, 95% CI] months for the high and low MTV total, respectively (Fig. 1). In multivariate analyses, a model including MTV total, SUV max and TLG total as imaging feature, and ICANS, C-reactive protein LD (CRP LD), LDH LD, lymphocytes count LD (Li LD) as clinical variables was able to successfully predict OS ( p = 0.019). Median progression-free survival (PFS) was 3 [1.31-NA, 95% CI] months and 11.06 [5.81-NA, 95% CI] months for the high and low MTV total, respectively. In multivariate analysis, a successful prediction of PFS ( p = 0.007) was achieved with a model including the same predictors that were used for OS. For the neurotoxicity assessment, a logistic regression model including six conventional PET parameters-MTV total, MTV DL,TLG total, TLG DL, median SUV DL, SUV max-two radiomic features,-entropy and entropy DL-and four clinical variables-CRP LD, LDH LD, Li LD and type of CAR-T cell treatment-was able to successfully predict the development of ICANS with an area under the curve of 0.971, a sensitivity of 0.813, a specificity of 0.846 and an accuracy of 0.828 (Fig. 2). Conclusions: Imaging features extracted from pre-infusion 18F-FDG PET/CT images in combination with several clinical features could predict survival and neurotoxicity in pts with DLBCL or PMBCL treated with CAR-T cell therapy. Quantitative features extracted from the PET/CT imaging exams may be useful for patient risk stratification and neurotoxicity prediction. Validation of these classifiers in independent datasets is warranted.

Upfront Radiation Therapy (RT) for Post-Stem Cell Transplant Multiple Myeloma (MM) Patients with Oligo-Relapse/Progressive Disease: Factors Associated with Favorable Outcomes

Introduction: Relapsed or refractory disease post-stem cell transplant (SCT) for Multiple Myeloma (MM) can be clinically challenging. For localized relapses, radiation therapy (RT) can represent an attractive treatment modality. However, data on outcomes with RT remains scarce. We investigated the impact of RT as a treatment modality in the setting of oligo-relapse and oligo-progressive plasmacytomas after SCT and explored prognostic factors associated with favorable long-term outcome Methods: In this single-institution retrospective analysis, we identified 31 MM patients who underwent upfront RT for oligo-relapse or oligo-progressive MM after SCT between 2000 and 2021. Patients were excluded if they had received systemic therapy for evidence of concurrent biochemical relapse prior to RT start. The treatment responses to stem cell transplantation (SCT) and RT were assessed following the response criteria established by the International Myeloma Working Group (IMWG), which includes the categories: complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). Additionally, we utilized the R-ISS staging system to classify patients into Standard-Risk (R-ISS I), Intermediate-Risk (R-ISS II), and High-Risk (R-ISS III) groups, to allow for a comprehensive evaluation of treatment efficacy and outcomes. Results: Disease and treatment characteristics for the cohort are summarized inFigure 1. Of the 27 patients with imaging available prior to SCT, 67% (18) were assessed with PET, 22% (6) with skeletal survey, 3.7% (1) with MRI/CT, 3.7% with CT, and 3.7% (1) with x-ray. Following SCT, 48% (13) of patients were noted to have radiographic progression, 23% (7) had sCR, 23% (7) had a CR, 10% had a serologic CR, and 45% (14) had a VGPR. Among the 18 patients with radiographic evaluation (in addition to bone marrow biopsy and/or labs) post-SCT, 67% (12) were in radiographic CR at time of re-staging. Median times from SCT to new site of oligo-relapsed disease (20, 64.5%) and pre-existing but inactive sites of oligo-relapsed MM (4, 12.9%) were 31 months (3.2-117.5) and 9 months (3.4-15.9), respectively. Oligo-progressive MM, defined as active sites of disease both pre- and post-SCT were present in 22.6% (7) of patients. Prior to RT, 94% (29) had PET/CT imaging, with a median SUV of 4.4 (2.6-7.2) for target lesions. Solitary bone (77%) and extramedullary (23%) disease were treated to median dose of 30 Gy (8-49 Gy). At first disease response assessment post-RT, 77% (24) of which was done with PET/CT imaging , 42% (13) achieved CR. Among the 18 patients that did not achieve CR, 15 subsequently achieved CR at a median time of 7 months (1.7-44.5). A majority of patients (87%) received systemic therapy post-RT, with a median number of lines of therapy post-RT of 3 (1-17). The remaining 13% (4) of patients did not receive additional systemic therapy post-RT and did not experience progression. Median overall survival for the full cohort was 38 months (3.5-37.9). Conclusions: Utilizing modern systemic therapies in combination with post-transplant RT for patients with limited refractory or relapsed MM is a promising therapeutic approach. For those that remain refractory or relapse in a single site RT local control merits consideration supported by our report. Further investigation to identify patients at highest risk of progression and who may therefore benefit most from RT would be valuable. We plan to conduct additional analyses on the radiographic characteristics that may portend high risk disease, with the ultimate goal of developing well-defined criteria for giving RT earlier.

Physiological Uptake Characteristics of Breast on 68Ga-FAPI-04 PET/CT.

Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological 68Ga-FAPI-04 uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological 68Ga-FAPI-04 uptake in normal breast. A total of 143 consecutive women with 68Ga-FAPI-04 PET/CT data were reviewed retrospectively. SUVmax, density and thickness of breast, as well as SUVmax of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs. Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast. There was no difference in 68Ga-FAPI-04 uptake between bilateral breasts (right: median, 1.14[IQR, 0.85-1.54] vs. left: median, 1.09[IQR, 0.86-1.54]; P = 0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median SUV, 3.91 [IQR, 2.85-4.35]) than those with expected moderate (early follicular, early luteal and late luteal phases; median SUV, 1.57 [IQR, 1.39-2.08]; P < 0.001) or low level (menopause and post-operation; median SUV, 0.98 [IQR, 0.83-1.21]; P < 0.001). Menstrual status was an independent predictors of breast SUV (r2 = 0.689, P < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status (P = 0.913).

Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter's Transformation: An International Multicenter Retrospective Study

Background: Aggressive lymphoma, most commonly large B-cell lymphoma (LBCL), arising in the setting of chronic lymphocytic leukemia (CLL) is known as Richter's transformation (RT), and is associated with poor outcomes. CD19 CART has revolutionized the treatment (tx) of LBCL, with durable responses for patients (pts) with relapsed/refractory disease. Pts with RT have been excluded from most major CD19 CART trials. Therefore, there is limited data describing outcomes of pts with RT receiving CD19 CART Methods: We conducted an international multicenter retrospective study of pts with RT who received CD19 CART approved for hematologic malignancies at 9 academic centers. RT was defined as pts with LBCL with preceding or concurrently diagnosed CLL. We collected pt, disease, and tx characteristics. Progression-free survival (PFS) and overall survival (OS) were measured from date of CD19 CART infusion and estimated using the Kaplan-Meier method. Cox regression model was used to associate prognostic factors with PFS and OS. Response was assessed by Lugano criteria. Results: 62 pts were included. Median age at CD19 CART infusion was 65 (range: 27-80). Median prior lines of therapy for CLL or RT were both 2 (CLL range: 0-10, RT range: 0-7). 52 (84%) pts previously received a Bruton tyrosine kinase inhibitor (BTKi) or BCL2 inhibitor (BCL2i) for CLL or RT. Median Ki-67 on pathology sample was 80% (range: 40-100), median SUV on brightest lymph node (LN) on PET-CT was 15.0 (range: 3-50.6), median size of largest LN was 3.8cm (range: 0-16), and median LDH prior to CD19 CART was 244 (range: 96-2878, ULN range: 190-271). Median time from apheresis to CD19 CART infusion was 33 days (range: 24-100), and 52 (84%) pts received bridging therapy. 40 (65%), 14 (23%), 7 (11%), and 1 (2%) pts received axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), and brexucabtagene autoleucel (brexu-cel), respectively. Overall response rate was 65%, with 29 (47%) and 11 (18%) pts attaining complete response (CR) and partial response (PR), respectively. After a median follow up of 24.1 months (mos) from CD19 CART infusion, the median PFS was 4.7 mos (95% CI: 2.3-6.9), and median OS was 8.5 mos (95% CI: 5.1-32.5) (Figure). Median duration of response was 14.5 mos (95% CI: 4.0-NR), with a median not reached (NR) (95% CI: 13.1-NR) for pts who achieved a CR, and a median of 2.3 mos (95% CI: 1.0-3.3) for pts who achieved a PR. Among 39 pts who died, 28 (72%) died due to progression of disease (PD), and 11 (28%) died for other reasons including 8 infections (4 COVID), 1 septic shock, 1 stroke, and 1 respiratory failure. The cumulative incidence of non-relapse mortality at 12 mos was 13% (95% CI: 6.2-23.4). 3 pts in a CR underwent allogeneic stem cell transplantation, 2 were alive at last known follow up (3.9 and 24.2 mos post-transplant), and 1 pt died from PD 21 mos post-transplant. 55 (89%) pts had CRS, with 9 (15%) grade ≥3 events. 43 (69%) pts had ICANS, with 23 (38%) grade ≥3 events. On univariable analysis, increasing Ki-67 and LDH were found to be associated with worse PFS and OS, and attaining a CR with CD19 CART was found to be associated with improved PFS and OS. On multivariable analysis, increasing Ki-67 and LDH, and greater number of prior lines of therapy for RT were independent prognostic variables for worse PFS and OS, and attaining a CR was associated with improved OS. All other variables, including type of CD19 CART product received, were not correlated with PFS or OS (Table). Conclusions: We report findings from the largest cohort of pts with RT who received CD19 CART. Of note, 84% of pts were exposed to either BTKi or BCL2i for the tx of CLL or RT. RT remains a disease of unmet need, as the median OS was 8.5 mos in this study. However, there is some progress made as historically the median OS for patients with RT previously treated with BTKi is 4 mos (Kittai et al AJH 2023). Given higher number of prior therapies is associated with worse OS, earlier use of CD19 CART in the RT disease course may be warranted. Our data support the use of CD19 CART for pts with RT, with durable disease control in a subset of pts, however there is clear room to improve and develop better therapies. Given observed high response rate to CD19 CART, along with most pts experiencing early relapse, allogeneic stem cell transplantation at response should be considered. Prospective clinical trials evaluating CD19 CART with novel agents for RT are currently ongoing.

Subcutaneous (SC) Mosunetuzumab (mosun) As First-Line Therapy for Patients (pts) with High Tumor-Burden Follicular Lymphoma (FL): First Results of a Multicenter Phase 2 Study

Introduction: Cytotoxic chemotherapy plus anti-CD20 antibodies is the current standard of care for pts with newly diagnosed high-burden FL. While effective, this approach is burdened by toxicities, including infections and second cancers, and up to 20% of pts progress within 2 years and have poor outcomes. Intravenous (IV) mosun is a CD20xCD3 bispecific antibody recently approved for the treatment of pts with relapsed or refractory FL based on remarkable efficacy data, and its activity may be even greater in chemotherapy-naïve patients. Furthermore, SC mosun proved as effective as, and possibly better tolerated than, the IV formulation while increasing administration efficiency and convenience. Here, we present the first results of a phase 2 multicenter trial of SC mosun in patients with untreated high-burden FL. Methods: Key eligibility criteria included: Age ≥18 years, stage 2-4 FL in need of therapy per GELF criteria, being fit for chemoimmunotherapy, adequate bone marrow and organ function. SC mosun was administered at the dose of 5 mg on D1 and 45 mg on D8 and D15 of C1, and 45 mg on D1 of each subsequent 21-day cycle. Premedication consisted of dexamethasone, diphenhydramine, and acetaminophen before each mosun dose during C1 and on C2D1 if cytokine release syndrome (CRS) occurred in C1. Subjects with ≥3 CRS risk factors (stage 3-4, bulky disease, bone marrow (BM) involvement, elevated LDH) received dexamethasone 10 mg for 3 days with each mosun dose in C1 and C2. Prophylactic hospitalization was not required. Treatment lasted 8 cycles in pts who achieved complete response (CR), and up to 17 in those with partial response. Response was assessed per the Lugano 2014 and LYRIC 2016 criteria. BM evaluation was mandated in pts with baseline BM involvement who achieved radiographic CR. CRS and neurotoxicity were graded per the 2019 ASTCT criteria. Results: Between July 2022 and July 2023, 43 pts were enrolled. Median age was 55 years (range 26-77), 40% of pts had bulky disease (≥7 cm), 25% had grade 3A FL, and 27% had a FLIPI score ≥3. The median SUV max was 11.5 (range 3.7-41.1)(Table). At the cutoff date of 07/21/2023, 4 pts were in screening, 22 were on treatment, and 13 completed treatment. Four pts discontinued therapy early due to progressive disease (1), or adverse events (AE) (3, one related to study drug). Out of 230 patient-cycles administered, 9 (4%) were delayed due to AEs, by a median of 13 days (range 7-17). Among 39 safety-evaluable pts, the most common treatment-emergent AE were injection site reaction (72%, all G1), CRS (51%), fatigue (33%), dry skin (33%), skin rash (26%), ALT elevation (23%), and AST elevation (21%). G≥3 neutropenia occurred in 4 pts (10%), while infections occurred in 10 pts (26%), and were G1-2 in 8 cases and G3 in 2 cases. One pt died of cardiac arrhythmia in the setting of COVID19-associated pneumonia. CRS occurred most commonly after C1D1 and was G1 in 18 pts (90%) and G2 in 2 (10%). Median time to onset of the first CRS episode was 31h (2-91). Hospitalization and tocilizumab were only required in the two pts who experienced G2 CRS. Twenty-six pts were evaluable for response (1 had concurrent neoplasm at first response assessment, 1 had indeterminate response (IR)3 per LYRIC criteria, and 15 are yet to be evaluated). The best overall response rate was 96% and the CR rate was 81%. All 22 CR were seen at the first response assessment (Figure). Similar response rates were observed among higher-risk subgroups, including pts with high-risk FLIPI (figure), grade 3A FL (ORR 100%, CR 75%), bulky disease (ORR 100%, CR 82%), or SUVmax ≥13 (ORR 83%, CR 83%)). At a median follow-up for response-evaluable pts of 6.0 months, 2 pts have experienced progression, one with CD20-negative FL at the end of therapy, the other with DLBCL diagnosed 6 weeks after treatment initiation on a left axillary lymph node with baseline SUV 41 and not previously biopsied. Conclusion: SC mosun demonstrated a manageable safety profile and highly encouraging efficacy in pts with newly diagnosed high-burden FL, including those with higher-risk disease. Assessment of durability of responses will require additional follow-up. Enrollment continues and updated data will be presented.

Does low-grade follicular lymphoma with high proliferation index require a different treatment strategy? A single center experience.

e19537 Background: Follicular lymphoma is the most common indolent non-Hodgkin lymphoma (NHL). It accounts for 35% of all NHL. FL is divided into three grades based on the proportion of centroblasts. The clinical aggressiveness increases from grade 1 to 3a, but this does not translate to a different therapeutic approach. Some FL patients have a high proliferation index despite having low grade. We assume patients with high proliferation index FL have a more aggressive disease requiring a different therapeutic approach. Here, we examine this theory in a cohort of 145 patients with follicular lymphoma. Methods: This is a retrospective study of patients diagnosed with FL between 01/01/2011 to 12/31/2021. Patients with histological grade 1-3a and reported proliferation index were included. Low grade is defined as grades 1 and 2. A high grade is defined as grade 3a. A high proliferation index (PI) is defined as Ki67 ≥ 30%. Patients were divided into three groups: low grade/high PI (LG/HP), low grade/low PI (LG/LPI), and high grade (HG). Variables collected included age, gender, race, Ann Arbor staging, PET SUV max, FLIPI score, and treatment details. The primary endpoint is progression-free survival. Secondary endpoints include overall survival (OS) and time to first treatment. Univariate and multivariate Cox regression models were used to analyze predictors of PFS. Survival estimates were calculated using the Kaplan-Meier method and compared using the Log-rank test. Results: We identified 145 patients with follicular lymphoma. The median age was 64. The majority were males (54.5%), whites (94.5%) and had Ann Arbor stage of 3 (42.8%). The median SUV max was 10.6. More than half of the patients were in the LG/LP (60%) compared with LG/HP (22.1%) and HG (17.9%). The median follow-up was 48.7 months. Male gender (HR 1.88, CI 1.04-3.4, p 0.03), Ann Arbor stage 3 (HR 4.3, CI 1.0-18.5, p 0.48) and 4 (HR 8.1, CI 1.9-34.8, p 0.005), PET SUVmax (HR 1.06, CI 1.9-1.1, p 0.001), and grade 3 disease (HR 2.2, CI 1.1-4.2, p 0.02) were associated with increased risk of progression. However, on multivariate analysis, only stage 4 (HR 13.1, 95% CI 1.7-104.0, p 0.02) was associated with an increased risk of progression. Adjusted 4-year PFS was 76% for LG/LP, 71% for LG/HG, and 49% for HG. There was no difference in median OS or time to treatment initiation. Conclusions: Our analysis showed that the median PFS for LG/HP patients is numerically worse than LG/LP, but it did not reach statistical significance. In contrast to previous reports, the trajectory of LG/HG is closer to LG/LP group rather than the HG group. Although outcomes are slightly worse for LG/HP compared with LG/LG, it does not justify a different treatment approach. However, a closer follow-up is warranted. Our study is limited by its retrospective nature and its inherent bias; using cox regression model to adjust for baseline characteristics would help mitigate this bias.

PLEASURABLE: Results and biomarkers analysis from the phase II study of dalpiciclib combined with pyrotinib and endocrine therapy (ET) in women with dual-receptor positive (ER+/HER2+) metastatic breast cancer (MBC).

1046 Background: In the front-line setting, our previous work demonstrated an impressive median progression-free survival (PFS) of 11.3 months with 66.7% response rate, and concluded a recommended phase 2 dose of pyrotinib 320mg/d, dalpiciclib (SHR6390, a novel CDK4/6i) 125mg/d, and letrozole 2.5mg/d for HR+/HER2+ MBC patients (pts) (Xichun Hu, FRONT ONCOL 2022). Results and biomarkers analysis from phase II dose expansion study are presented. Methods: ER+/HER2+ MBC Pts eligible for first- or second-line treatment were enrolled to receive dalpiciclib combined with pyrotinib and ET (letrozole or fulvestrant determined by physician’s choice). The primary endpoint was objective response rate (ORR). For biomarkers analysis, 68Ga-HER2 affibody, pre-treatment tissue-derived DNA and circulating tumor DNA (ctDNA) were assessed by PET/CT, and next-generation sequencing (NGS), respectively. Results: As of January 19, 2023, 48 pts were enrolled. 17 pts (35.4%) were treatment naïve, and 31 pts (64.6%) had received prior trastuzumab. The ORR was 68.1% (32/47) and disease control rate was 100% (47/47). In trastuzumab-naïve and trastuzumab-pretreated patients, ORR was 81.3% (13/16) and 61.3% (19/31), respectively. PFS and OS data were not mature by cut-off date. No new safety signals were observed. The most frequent treatment-related adverse events were neutropenia (95.8%; G3:60.4%, G4:6.3%), leukopenia (91.7%; G3:45.8%), diarrhea (87.5%; G3:2.1%), anemia (79.2%; G3:4.2%), oral mucositis (68.8%, G3:2.1%) and platelet count decreased (41.7%; G3:2.1%, G4:2.1%). The heterogeneity of 68Ga-HER2 affibody uptake was observed among patients, both at baseline (N=16，median SUV max 7.5, range, 2.3-34.9) and after 2 cycles of therapy (N=12，median SUV max 4.0, range, 0-14.9). All patients with a decline in 68Ga-HER2 affibody uptake (N=8) achieved partial response, while the uptake in non-responders was elevated (N=2). NGS was conducted to detect somatic and germline mutations in baseline tissue (n=10) and ctDNA (n=10) samples. Two patients with BRCA mutation (one had somatic BRCA1/ 2 mutation and another with germline BRCA2 mutation) had no tumor response. Conclusions: The chemotherapy-sparing regimens showed significant anti-tumor activity for ER+/HER2+ MBC pts in the front-line setting. The 68Ga-HER2 affibody PET/CT may be a potential predictive biomarker of therapy response. Additional analysis including correlation of biomarkers with long-term outcomes is underway. Clinical trial information: NCT03772353 .

A single‐center experience of low‐dose radiotherapy for primary extranodal marginal zone lymphoma of bronchus‐associated lymphoid tissue (BALT)

Introduction: Extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue (BALT) is a rare cancer for which optimal treatment strategies are not well defined. Retrospective analyses show equivalent or superior outcomes with surgical resection compared to systemic therapy or active surveillance. Despite a well established role for radiotherapy in the management of other types of extranodal marginal zone lymphoma (MZL), its role in BALT lymphoma is underexplored. Methods: We screened 153 patients with a diagnosis of primary BALT lymphoma treated at a single institution from 1995 to 2022. Inclusion criteria comprised patients aged 18 years or older, histologically confirmed BALT lymphoma, and receipt of radiotherapy at initial presentation or disease progression/recurrence. We excluded patients with synchronous evidence of lymphoma involving non-thoracic extranodal sites and/or lymphadenopathy outside of the mediastinum and hilum, as these patients might represent MZL with secondary lung involvement as opposed to primary BALT lymphoma. All patients underwent baseline PET/CT staging. We extracted patient, tumor, imaging, and treatment characteristics from the electronic medical record. We defined active surveillance as at least 3 months of follow up prior to initiating active therapy combined with documentation of this plan in the medical record. We assessed treatment response using the RECIL 2017 criteria. Results: We report the largest to date single-center retrospective analysis of 13 patients (median age 67 years, range 33–84 years) with localized BALT lymphoma treated with radiotherapy. The median tumor size was 3.6 cm (range 0.8–8.2 cm) with a median SUV of 3.9 (range 1.3–11.4). Most patients (n = 8, 62%) received radiotherapy for BALT lymphoma after failing first-line treatment, including active surveillance (n = 3), surgical resection (n = 2), or systemic therapy (n = 3). Of 15 irradiated lesions, most (n = 10, 67%) received very low-dose radiotherapy (VLRDT) of 4 Gy (range 4–36 Gy). With a median follow-up of >50 months, only 3 patients experienced progression of disease, none within the irradiated field (1 following VLDRT and 2 following full-dose RT). Among all treated lesions, the overall response rate was 100% (n = 5, 33% partial response [PR] and n = 10, 67% complete response [CR]). Among 10 lesions treated with VLDRT, 6 (60%) achieved CR; among 5 lesions treated with full-dose RT, 4 (80%) achieved CR. There were no events of secondary lung cancers within or in proximity to the irradiated field. Conclusions: Radiotherapy, including VLDRT, is a feasible, well tolerated, non-invasive and effective treatment strategy for primary BALT lymphoma that can be considered in both the upfront and recurrent treatment settings. The research was funded by: National Cancer Institute (P30 CA008748) Keywords: Extranodal non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

PD10-04 SUVMAX OF THE PRIMARY PROSTATE LESION ON THE PSMA PET CT: AN INDICATOR OF AGGRESSIVE PATHOLOGY

You have accessJournal of UrologyCME1 Apr 2023PD10-04 SUVMAX OF THE PRIMARY PROSTATE LESION ON THE PSMA PET CT: AN INDICATOR OF AGGRESSIVE PATHOLOGY Amandeep Arora, Archi Agarwal, Mahendra Pal, Ganesh Bakshi, Venkatesh Rangarajan, Gujela Ajit, Santosh Menon, and Gagan Prakash Amandeep AroraAmandeep Arora More articles by this author , Archi AgarwalArchi Agarwal More articles by this author , Mahendra PalMahendra Pal More articles by this author , Ganesh BakshiGanesh Bakshi More articles by this author , Venkatesh RangarajanVenkatesh Rangarajan More articles by this author , Gujela AjitGujela Ajit More articles by this author , Santosh MenonSantosh Menon More articles by this author , and Gagan PrakashGagan Prakash More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003250.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA PET CT scans are being increasingly utilized in the staging evaluation of prostate cancer. However, there is limited data regarding the utility of the standardized uptake value (SUVmax) of the primary prostate lesion in the PSMA PET scan. Here, we evaluated whether the SUVmax of the primary prostate lesion can indicate aggressive pathological features in patients undergoing radical prostatectomy (RP) with an extended pelvic nodal dissection (PLND). METHODS: We retrospectively reviewed a prospectively maintained institutional database for prostate cancer patients from 2015-2022 who had a PSMA PET scan for their staging evaluation followed by a RP with PLND. Data was collected for clinico-pathological variables. The SUVmax of the primary lesion in the prostate was noted & compared across the pathological Gleason grade groups (GGG). We also checked whether the SUVmax had an association with Gleason upgrading & pathological nodal status. RESULTS: A total of 205 patients were included & were stratified into the following clinical risk groups based on MRI & PSMA-PET scans: 6 (2.9%) low-risk, 49 (23.9%) intermediate-risk, 46 (22.4%) high-risk localized, 89 (43.4%) locally-advanced node-negative & 15 (7.3%) node-positive patients. The median SUVmax of the primary prostate lesion for pathological GGG 1, 2, 3, 4 & 5 were 6.45, 11.3, 18.11, 25.51 & 24.37 respectively (p<0.001). For the 153 patients with a Gleason score 6-7 on transrectal biopsy, 19 patients had an upgrading of their score to >8 on the final pathology. The median SUV max of the prostate lesion in these 19 patients was significantly higher [median 22.37 (IQR 15.5–33.1)] than that in the remaining 134 patients with biopsy Gleason score 6-7 who did not have an upgrading to >8 on the final pathology [median 11.3 (IQR 7.4–17.5)]; p<0.001 (Figure 1). Also, the median SUVmax of the primary prostate lesion in patients who were true negatives for nodes, as per the PSMA-PET scan & final pathology, was significantly lower (12.8 vs 26.4, p<0.001) than that in patients who were false negative (cN0 on PSMA but pN+ in final pathology). CONCLUSIONS: Higher SUVmax of the primary prostate lesion is an indicator of aggressive pathological behaviour in the form of Gleason upgrading positive pelvic nodal status. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e327 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amandeep Arora More articles by this author Archi Agarwal More articles by this author Mahendra Pal More articles by this author Ganesh Bakshi More articles by this author Venkatesh Rangarajan More articles by this author Gujela Ajit More articles by this author Santosh Menon More articles by this author Gagan Prakash More articles by this author Expand All Advertisement PDF downloadLoading ...

Investigating Metabolic Response after CAR-T Therapy and Bridging Radiotherapy for Relapsed/Refractory B-Cell Lymphoma

Introduction: For patients with aggressive relapsed/refractory B-cell lymphoma (R/R BCL) undergoing CAR-T therapy, metabolic treatment response assessed at the 1-month interval following CAR-T infusion is associated with likelihood of disease progression (Kuhnl A, et al. Blood Adv 2022). In particular, SUV max on 1-month 18F-FDG positron emission tomography (PET) imaging is predictive of disease progression (Zaki A, et al. Blood Adv 2022). However, for patients who undergo bridging radiotherapy (RT) prior to CAR-T infusion, it remains unclear how to interpret metabolic activity for irradiated sites on surveillance PET imaging following CAR-T. We sought to characterize metabolic activity after CAR-T and bridging RT in a cohort of patients with R/R BCL. Methods: This IRB-approved retrospective cohort study included patients with R/R BCL who underwent bridging RT prior to CAR-T infusion at a single institution from January 1, 2019 to April 30, 2022. We measured baseline patient characteristics, treatment factors, and PET metrics prior to bridging RT. We then assessed tumor metabolic activity on surveillance PET imaging following CAR-T infusion until the time of disease progression (defined as Deauville 5 disease) or last follow up. Results: We identified 10 patients who completed bridging RT prior to CAR-T infusion with at least one post-CAR-T disease assessment with PET imaging. Median follow up was 152 days from CAR-T infusion (range: 31-1095). Most patients (90%) had bulky disease (≥7.5 cm) and all had elevated LDH at baseline. Bridging RT dosing ranged from 20-38.5 Gy (median: 20 Gy) over 5-14 fractions (median: 5 fractions). Bridging RT fields were directed at bulky disease sites for 8 of 9 patients with bulky disease. The median metabolic tumor volume (MTV) irradiated with bridging RT was 149 mL (range: 26-803) and the median proportion of total MTV irradiated was 97% (range: 8.7-100). The median time between pre-bridging RT PET imaging and CAR-T infusion was 49 days (range: 37-124) and the median time between the end of bridging RT and CAR-T infusion was 12 days (range: 5-106). On pre-bridging RT PET, the median SUV max in the irradiated field was 23.3 (range: 9.1-36.1) (Figure 1). On 1-month post-CAR-T PET, the median SUV max in the irradiated field decreased to 3.2 (range: 0-6.1) and median delta SUV max was -87% (range: -68% to -100%). At the 1-month post-CAR-T interval, 40% of patients had a complete metabolic response (Deauville 3 or below), 40% had Deauville 4 disease, and 20% had Deauville 5 disease. Among the 4 patients with Deauville 4 disease at 1-month post-CAR-T, 3 patients developed complete metabolic responses and 1 patient had persistent Deauville 4 disease on subsequent PET imaging. No patients in the cohort developed disease progression within the irradiated fields. At last follow up, 3 patients had developed Deauville 5 disease, and for 2 of the 3 patients, areas of disease progression included unirradiated sites of disease that were present on pre-bridging RT PET imaging. Conclusions: In this small retrospective cohort of patients undergoing bridging RT prior to CAR-T therapy for R/R BCL, patients with concern for refractory disease on initial imaging assessment demonstrated complete response or stable disease on subsequent follow up imaging. Caution may be warranted in interpreting metabolic activity levels on initial post-CAR-T surveillance PET imaging, and validation in larger cohorts is needed to better understand metabolic activity dynamics in disease sites treated with bridging RT prior to CAR-T therapy. Figure 1. SUV Max in Disease Sites Treated with Bridging RT* *Each line corresponds to one patient treated with bridging RT prior to CAR-T therapy. SUV max plotted on the vertical axis reflects metabolic activity within the irradiated fields. Time intervals indicated in months on the horizontal axis reflect the approximate time from CAR-T infusion with the exact range in days indicated in parentheses. The magnification box demonstrates metabolic activity at the 1-month post-CAR-T interval with corresponding Deauville score indicated by color. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Clinical Outcomes of Proton Beam Therapy for Unresectable Locally Advanced Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> We retrospectively researched on the treatment outcomes and assessed the efficacy of proton beam therapy (PBT) for unresectable locally advanced pancreatic cancer (LAPC). <h3>Materials/Methods</h3> Fifty-four patients who were diagnosed unresectable LAPC and administered PBT between April 2009 to March 2020 at our institution. Patients who could not completed PBT, had new distant metastases during treatment, and did not have enough follow-up time were excluded in this study. Statistical analyses were performed by calculating overall survival rate (OS) and local control rate (LC). Median survival time (MST) was analyzed by several following factors; maximum standardized uptake values (SUV_max) of FDG-PET evaluation, performance status (PS), tumor site, total irradiation dose, and combination use of chemotherapy. Treatment toxicities were evaluated by Common Terminology Criteria for Adverse Events (CTCAE ver.5.0). OS, MST, and LC were analyzed using the Kaplan-Meier method and log-rank test. The cut-off values for SUV_max and tumor diameter were estimated using the receiver operating characteristic (ROC) curve and area under the curve (AUC) based on MST. <h3>Results</h3> This study included 28 men and 26 women whose median age was 67.5 years (range, 40 to 88 years). All patients were clinical stage III LAPC according to the Union for International Cancer Control (UICC) TNM staging system (8th edition). Median follow-up time was 17.4 months (range, 4.0 to 89.7 months). The median total dose was 67.5GyE (range, 50-77 GyE/25-35 fractions). The median tumor diameter was 36.5mm (range, 15 to 90 mm). The median SUV_max was 5.85 (range, 2.1 to 27.6). Chemotherapy regimens during PBT were following; 24 patients were gemcitabine alone, 5 were tegafur-gimeracil-oteracil (TS-1) alone, 17 were paclitaxel and TS-1. Eight patients did not receive chemotherapy because of their poor general condition. The One-year, 2-year, 3-year OS were 74.1%, 33.3%, 10.8%, respectively. The One-year, 2-year, 3-year LC were 89.0%, 84.6%, 84.6%, respectively. The MST was 17.1 months. Only one patient survived longer than 5 years. The cut-off values were estimated for SUV_max: 4.8 and tumor diameter: 37mm. Two-year OS based on PS-score group were following; PS 0/1/2: 26.1/ 13.4/8.0 months, respectively with significant differences (each group P<0.01). Treatment related acute toxicities were neutropenia (Grade1/2/3: 2/6/17 patients), leukopenia (Grade1/2/3: 1/4/11 patients), thrombocytopenia (Grade1/2: 1/4 patients), respectively. Late toxicity was gastrointestinal ulcer (Grade1/2: 2/2 patients). No Grade 3 or higher late adverse events were observed. <h3>Conclusion</h3> PBT combined standard chemotherapy achieved excellent local control. However, it did not control systematic tumor progression. PS score at first visit could be important prognostic factor.

11C-Choline Positron Emission Tomography-Detected Prostate Cancer Thoracic Metastases

<h3>Purpose/Objective(s)</h3> Prostate cancer metastasis to the chest is considered a poor prognostic indicator but is not well-described in the era of molecular imaging. We evaluate the radiographic features, management, and outcomes associated with prostate cancer thoracic metastases detected by ¹¹C-choline positron emission tomography/computed tomography (PET/CT). <h3>Materials/Methods</h3> A prospectively maintained database of 6,118 prostate cancer patients with ¹¹C-choline PET/CT findings was used to identify thoracic metastases detected from 2011 to 2021. Biopsy confirmation was not required, but patients with a negative biopsy were excluded from analysis. Patient, disease, and treatment characteristics were identified and analyzed for their association with outcomes. <h3>Results</h3> Sixty-seven patients (1.1% of those in the database) were included with a median follow-up of 45 months (IQR: 17-57.5) from metastasis detection. Primary local treatment was radical prostatectomy in 36 (55.2%) patients and radiotherapy in 21 (31.3%). Thirty-seven patients (55.2%) had histologic confirmation. Median interval from initial diagnosis to thoracic metastasis detection was 66 months (IQR: 38-107). Thirty-nine patients (58.2%) were oligometastatic (≤5 lesions) and 23 (34.3%) had previously diagnosed extrapulmonary metastases. Lesions were more often in the lung parenchyma (80.5%) than mediastinum (9.8%), hila (8.5%), or pleura (1.2%). Median greatest dimension was 1.0 cm (IQR: 0.8-1.3). Eight patients (11.9%) had lesions detectable on CT without PET avidity, five of whom had histologic confirmation. Median SUV_max was 3.3 (IQR: 2.5-4.4) for all ¹¹C-choline PET/CT-avid lesions and 3.9 (IQR: 2.5-4.6) in histologically confirmed lesions. Fifty-seven patients (85.1%) were managed with systemic therapy. Eighteen lesions in 17 patients were managed with local therapy, 15 surgically and 3 with radiotherapy. Among the 39 patients with oligometastatic disease, median time to subsequent radiographic progression was 28 months compared to 14 months in those with widely disseminated disease. Median time to progression in the 17 men receiving metastasis-directed therapy was 33 months, despite a lower rate (52.9%) of systemic therapy use in this group. Forty-nine (73.1%) patients were alive at last follow-up. <h3>Conclusion</h3> We provide the largest single institution report to date of patients with ¹¹C-choline PET/CT-detected prostate cancer thoracic metastases. In well-selected men, metastasis-directed therapy may delay time to radiographic progression and initiation of systemic therapy. At the time of detection, a third of patients have diffuse pulmonary involvement. Despite this finding, survival outcomes remain encouraging with nearly three-quarters of patients alive at a median follow-up of 45 months. Efforts are ongoing to identify clinicopathologic and molecular characteristics which may guide management in this population.

Impact of Time-to-Treatment on Lung SBRT Outcomes: Histology Matters!

<h3>Purpose/Objective(s)</h3> "Time-to-treatment" (TTT) is considered an indicator of quality care that has been postulated to affect lung cancer outcomes. The process by which an early stage medically inoperable lung cancer patient (pt) is deemed appropriate for lung stereotactic body radiation therapy (SBRT) typically involves a multi-disciplinary assessment over extended time. This study analyzed a large single institution registry to explore the impact of TTT on SBRT outcomes. <h3>Materials/Methods</h3> From an IRB-approved lung SBRT registry, we identified 1573 pts treated definitively for early-stage lung cancer between 2003 and 2020. TTT was defined as elapsed months between date of diagnosis (date of biopsy or date of PET CT in cases of radiographic diagnosis) and SBRT start date. Fine-Gray's Test was employed to evaluate the effect of TTT on local control (LC) and freedom from disease progression (FFP), and the long rank test was used for overall survival (OS). Cumulative incidence rates with death as competing event were calculated for LC and FFP. Actuarial analysis as used to calculate OS rates. <h3>Results</h3> Median follow-up was 22.9 months. Median age at SBRT start in years was 74.5 (range 35-98), median KPS was 80 (range 40-100), 52.3% of pts were female and 84.0% were white. Median tumor size and median PET SUV max were 2.2 cm (range 0.4-10.5) and 7.5 (range 0.8-56), respectively; 88.3% of pts were stage I. Of 75.7% pts with biopsies, 30.6% were adenocarcinomas (AC), 27.8% had squamous carcinoma (SqC). Median SBRT dose was 50 Gy in 5 fractions (40.5% cases). The 2-year rates of LC, FFP and OS for all pts were 6.5%, 76.3%, and 62.6%, respectively. Median TTT was 1.7 months (range 0.2-18.1). Using a cut-off of 1.5 months to compare patients receiving upfront vs delayed treatment, there was no difference in LC (p=0.5644), FFP (p=0.1976) or OS (p=0.3018) between the two groups. Of 1038 pts with histologic diagnosis, TTT was associated with OS but not LC or FFP for SqC pts (p=0.0422), and with no AC outcomes. An association of TTT with FFP for pts aged 70-79 (p=0.0302) was seen but otherwise no significant differences were noted in TTT outcomes for pts stratified by T stage, age in decades or KPS. Pt and tumor characteristics were balanced between cut-off cohorts. <h3>Conclusion</h3> Although TTT per se was not associated with altered lung SBRT outcomes in this cohort of nearly 1600 early-stage inoperable lung cancer pts, increasing TTT was found to have a negative association with OS for SqC pts on subset analysis. Previous studies have suggested impaired LC for SqC with SBRT although this was not seen in either of the TTT cut-off cohorts. Further work is warranted to determine how TTT may affect SBRT outcomes in the SqC population.

Prevalence and Risk Factors of Retro-Styloid Lymph Node Metastasis in Oropharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> The assessment of the prevalence of retro-styloid lymph node metastasis (RSLNM) and associated risk factors may guide the selection criteria of level VIIb for inclusion in the target volume for high-precision radiotherapy (RT). However, data clarifying the selection criteria have not yet been established. We evaluated the prevalence of level VIIb RSLNM and associated risk factors in patients with oropharyngeal carcinoma (OPC). <h3>Materials/Methods</h3> Two board-certified radiation oncologists with an experience of 15 and 17 years in diagnosing and treating head and neck cancers retrospectively reviewed pretreatment [¹⁸F]-fluoro-2-deoxy-D-glucose–positron emission tomography/computed tomography (CT) along with contrast-enhanced thin slice CT and magnetic resonance (MR) images of 137 patients pathologically confirmed as having OPC who underwent RT. Observers independently evaluated the images without prior knowledge regarding the clinical information of the patients, and disagreements were resolved by consensus. The location of LN was confirmed on the planning CT images. In addition to RSLNM assessment, which includes the short-axis diameter and the maximum standardized uptake value (SUV_max), long-axis diameter of the largest LN in the upper limit of ipsilateral level II (caudal edge of the C1 lateral process) was recorded. Fisher's exact test and logistic regression analyses were made to determine the risk factors of RSLNM. <h3>Results</h3> RSLNM was confirmed in 18 (13%) patients. All RSLNMs were located within level VIIb on the planning CT images. The median short-axis diameter and SUV_max of RSLNM were 11 mm (range 8–15) and 5.2 (range, 1.9–9.4), respectively. No patients exhibited LNM in contralateral level VIIb. Furthermore, no patients with negative or single ipsilateral cervical LNM had RSLNM. Fisher's exact test revealed that smoking status (p = 0.027), multiple ipsilateral cervical LNM (p = 0.045), and LN ≥ 15 mm in the upper limit of ipsilateral level II (p < 0.001) were significantly associated with RSLNM. Logistic regression analyses revealed that the only factor significantly associated with RSLNM was LN ≥15 mm in the upper limit of ipsilateral level II (odds ratio: 977.297, 95% CI: 57.629–16573.308; p < 0.001). <h3>Conclusion</h3> RSLNM is relatively common in patients with OPC with a prevalence rate of approximately 10%. The prevalence of RSLNM in patients with negative or single ipsilateral cervical LNM and contralateral RSLNM is extremely low; therefore, level VIIb can be excluded from the target volume in such patients. LNs ≥ 15 mm in the upper limit of ipsilateral level II is a risk factor for RSLNM. Ipsilateral level VIIb should be included in the target volume for patients with this risk factor.

Comparison of 18 F-PSMA-1007 PET/CT With 68 Ga-PSMA-11 PET/CT for Initial Staging in Intermediate- and High-Risk Prostate Cancer.

This study aimed to compare 18 F-PSMA-1007 PET/CT with 68 Ga-PSMA-11 PET/CT for initial staging in intermediate- and high-risk prostate cancer (PCa) patients. Forty treatment-naive, biopsy-proven, intermediate- or high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68 Ga-PSMA-11 and 18 F-PSMA-1007 (within 2 weeks). Assessment of both set of images included delineating number and characteristics of lesions, measurement of tracer uptake (SUV max ), miPSMA scoring, and PET-based stage categorization. Intraprostatic lesions were detected in all patients by both tracers with concordant PET-based T stage. Median SUV max of the dominant PSMA-positive prostatic lesions was not significantly different with 18 F-PSMA-1007 and 68 Ga-PSMA-11 (19.9 vs 19.4, P = 0.127, n = 40). Prostatic miPSMA scores were similar in 31/40 (77.5%) patients with both tracers (weighted κ = 0.71). In 23/40 (57.5%) patients, regional lymph nodes (n = 171) were detected by both tracers. Few additional PET-positive regional lymph nodes (n = 3) were exclusively detected by 18 F-PSMA in 2 patients without altering PET-based N stage. Extraregional lymph nodes (n = 123 in 17/40 patients) and visceral metastatic lesions (n = 18 in 3/40 patients) were detected concordantly by both tracers. PET-positive marrow based and skeletal metastases (n = 71) were detected in 14/40 (35%) patients by both tracers. Few additional marrow and skeletal lesions (n = 7) were exclusively detected on 18 F-PSMA-1007 in 5/14 patients, potentially upstaging PET-based M stage in 2/5 patients. Both radiotracers showed excellent interreader agreement for region-wise detection of lesions. Our results suggest that 18 F-PSMA-1007 PET/CT is comparable to 68 Ga-PSMA-11 PET/CT in detecting primary and metastatic lesions of PCa.