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Background: To compare suspected areas of cancer involvement based on the findings of CT and FDG-PET/CT in patients with inflammatory breast cancer (IBC) and to determine if discrepancies would modify radiation therapy treatment fields. Methods: This is a retrospective study of 29 consecutive female patients with IBC (median age 49 years, range 28-78) who had both CT and PET/CT scans prior to the initiation of systemic therapy. CT and PET/CT scans were obtained within a median of 3 days (range 0 -64). CT and PET/CT scans were independently reviewed by a board-certified radiologist (PD) and a board-certified nuclear medicine physician (HJ), respectively. Findings were recorded by anatomic site and graded as negative, equivocal or positive for malignancy. Radiation fields were then determined by a breast radiation oncologist (JB) after separately reviewing the CT and PET/CT images. Discrepancies between the two modalities were recorded. The study was approved by the hospital institutional review board. Results: Seven of 29 patients (24%) had discrepant findings that likely would have resulted in a modification of radiation treatment fields and/or radiation dose. In four patients, internal mammary nodal involvement was suspected on PET/CT but not on CT. In two of these four patients, PET/CT also detected additional disease (supraclavicular in one patient and chest wall in the other) that likely would have required a change in radiation field and/or dose. Another patient had subpectoral adenopathy on PET/CT that was not considered abnormal on CT. One patient had equivocal findings in the infraclavicular region on CT which was negative on PET/CT. In one patient, body habitus limited the CT evaluation; more extensive infiltrative soft tissue and nodal disease was seen on PET/CT. In four patients, there were discrepant findings for distant disease that likely would have resulted in a change in management or additional imaging studies. In two of these cases, PET/CT showed a clearly positive finding that was negative or equivocal on CT. In an additional two cases, equivocal PET/CT findings would have resulted in additional testing that would not have been recommended by CT alone. In another 4 cases, metastatic disease was suspected based on CT, but additional sites (all in bone and not seen on CT) were suspected on PET/CT. Conclusions: Inflammatory breast cancer patients have a high probability of presenting with extensive local/regional disease and distant metastases. In our IBC population, PET/CT imaging would have likely resulted in a change of radiation field or dose in 7 of 29 (24%) patients. Additionally, in four instances PET/CT suspected additional metastatic disease (14%). These discrepancies most commonly involved inclusion of an internal mammary nodal radiation field and identification of distant metastases. Pathologic verification of abnormal findings is necessary to verify these results. PET/CT imaging should be considered a standard component of radiographic staging for patients with IBC. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors.Methods: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here.Results: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame.Conclusions: Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .). [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) is a virulent subtype of locally advanced breast cancer that accounts for 1-5% of all breast cancers diagnosed in the United States. Conventional therapy for IBC (preoperative chemotherapy, mastectomy, radiation therapy) results in a median 5 year overall survival of 50%, which supports the need for investigation into the molecular distinctiveness of IBC, with the ultimate goal of developing effective therapeutic agents that target these molecular changes. Some of the distinctive molecular characteristics of IBC include the presence of a substantial proportion of CD44+/CD24- breast cancer cells that express stem cell-like characteristics, over-expression of Ecadherin, and extensive formation of tumor emboli. Examination of breast tumors and preclinical data suggests that the JAK2/STAT3 pathway is active in CD44+/CD24- breast cancer cells, and is stimulated by various mechanisms associated with IBC, such as high IL -6 levels. We investigated the role of JAK2/STAT3 activation in IBC as preclinical evidence to pursue JAK2 targeted therapy for IBC in a clinical setting. Methods: Using de-identified breast tissue specimens from both untreated and treated IBC patients obtained on a protocol approved by our institutional review board; we performed immunohistochemical (IHC) and multicolor immunofluorescence analysis to detect the presence of CD44+/CD24- cells and the fraction of activated phospho-STAT3 (pSTAT3). The number of cells positive for pSTAT3 was assessed pre and post-treatment. We also analyzed the status of CD44+/CD24- cells and pSTAT3 in SUM149 and SUM190 IBC cell lines, and an IBC xenograft model (IDC31) derived from primary tumor obtained from an IBC patient. We tested the efficacy of multiple different JAK2 inhibitors to inhibit the growth and viability of cell cultures and xenografts. Results: All IBCs were highly enriched in CD44+/CD24- cells, with approximately 80% of all cancer cells within tumors displaying this phenotype. About 85% of IBC cases show activation of pSTAT3, and a significant fraction (40%) of CD44+/CD24- cells were pSTAT3 positive. Interestingly, the fraction of pSTAT3+ cells was lower in the CD44+/CD24- cells in post treatment samples from triple negative but not from luminal tumors. JAK2 inhibition significantly decreased the proliferation of pSTAT3+ IBC cells lines in vitro and the growth of pSTAT3+ xenografts including the IBC model ICD31. Discussion: Specific molecular characteristics of IBC result in a unique and virulent disease course. Based upon a predominance of CD44+/CD24- breast cancer stem cells present in IBC, we investigated the JAK2/STAT3 pathway in IBC tissue specimens, cell lines and an IBC xenograft model. Our preclinical data demonstrates a highly active JAK2/STAT3 pathway in IBC which lends itself to exploration of the efficacy of a JAK2 inhibitor in the treatment of this disease. A phase I/II study is underway to evaluate combination ruxolitinib and chemotherapy for the primary treatment of triple negative IBC. [ABSTRACT FROM AUTHOR]

Background: While the survival of patients with inflammatory breast cancer (IBC) is dictated by the status of their distant metastases, local/regional control remains an important component of quality of life. We have sought to determine patterns of local/regional recurrence (LRR) in patients presenting with inflammatory breast cancer. Methods: The medical records of 92 patients (pts) diagnosed with IBC from 1997 until 2007 were reviewed. Pt cohorts were stratified by disease burden at presentation (metastatic or local/regional) and their tumor, treatment, and disease course were analyzed. Primary outcomes were time from diagnosis to LRR, time to distant recurrence, and overall survival (OS). Median follow-up (MFU) for the entire cohort was 6 years (yrs) (range 0.1 to 12.7 yrs); for those patients who presented with metastatic disease versus only local/regional disease, MFU is 2 yrs and 6 yrs, respectively. This study was approved by the hospital institutional review board. Results: Median age at diagnosis was 49 yrs (range 24 to 72). 68 (74%) patients were without evidence of metastatic disease on presentation. With 6yr MFU, 40/68 (59%) had disease recurrence at either local or distant sites, and 15/68 (22%) had documented LRR, either as the first or subsequent site of recurrence. Estimated 5yr OS is 64%. 24 (26%) pts presented with metastatic disease (lung, liver, distant lymph nodes, pleura). All of the 24 pts presenting with metastatic disease developed systemic disease progression; 12/24 (50%) also developed LRR, and for 9/12 pts the LRR was first progression or concurrent with distant progression. Eleven of the 24 pts did not receive radiation or surgery; and within this cohort, 7 (64%) pts developed LLR at a median time of 9 months after diagnosis. Six pts received radiation therapy without surgery; 3/6 (50%) developed LRR. One pt had surgery alone; this patient was not known to have LRR, although had limited follow-up. Six pts received radiation therapy and surgery; 1 for palliation and 5 to prevent LRR. Of these 5 pts, 1/5 (20%) developed LRR that extended to the contralateral breast at 1.2y after diagnosis. Among the 24 patients, the cumulative incidence of LRR was 29%, 37%, and 43% at 1yr, 2yr, and 3yr (accounting for competing risk of death). The median OS was 2.9 yrs and estimated 5yr OS was 36%. Conclusions: Pts with inflammatory breast carcinoma presenting with metastatic disease are at high risk for local/regional disease progression. Aggressive local therapy should be considered to prevent symptoms of uncontrolled local disease, despite an uncertain impact upon OS. [ABSTRACT FROM AUTHOR]

Purpose: The recently released EANM/SNMMI guideline, endorsed by several important clinical and imaging societies in the field of breast cancer (BC) care (ACR, ESSO, ESTRO, EUSOBI/ESR, EUSOMA), emphasized the role of [ 18 F]FDG PET/CT in management of patients with no special type (NST) BC. This review identifies and summarizes similarities, discrepancies and novelties of the EANM/SNMMI guideline compared to NCCN, ESMO and ABC recommendations., Methods: The EANM/SNMMI guideline was based on a systematic literature search and the AGREE tool. The level of evidence was determined according to NICE criteria, and 85 % agreement or higher was reached regarding each statement. Comparisons with NCCN, ESMO and ABC guidelines were examined for specific clinical scenarios in patients with early stage through advanced and metastatic BC., Results: Regarding initial staging of patients with NST BC, [ 18 F]FDG PET/CT is the preferred modality in the EANM-SNMMI guideline, showing superiority as a single modality to a combination of contrast-enhanced CT of thorax-abdomen-pelvis plus bone scan in head-to-head comparisons and a randomized study. Its use is recommended in patients with clinical stage IIB or higher and may be useful in certain stage IIA cases of NST BC. In NCCN, ESMO, and ABC guidelines, [ 18 F]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [ 18 F]FDG PET/CT can replace conventional imaging for staging patients with high-risk and metastatic NST BC. During follow up, NCCN and ESMO only recommend diagnostic imaging if there is suspicion of recurrence. Similarly, EANM-SNMMI states that [ 18 F]FDG PET/CT is useful to detect the site and extent of recurrence only when there is clinical or laboratory suspicion of recurrence, or when conventional imaging methods are equivocal. The EANM-SNMMI guideline is the first to emphasize a role of [ 18 F]FDG PET/CT for assessing early metabolic response to primary systemic therapy, particularly for HER2+ BC and TNBC. In the metastatic setting, EANM-SNMMI state that [ 18 F]FDG PET/CT may help evaluate bone metastases and determine early response to treatment, in agreement with guidelines from ESMO., Conclusions: The recently released EANM/SNMMI guideline reinforces the role of [ 18 F]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: There is much literature about the role of 2-[ 18 F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject., Purpose: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA)., Methods: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[ 18 F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria., Results: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[ 18 F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[ 18 F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[ 18 F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[ 18 F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising., Conclusion: 2-[ 18 F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios., (© 2024. The Author(s).)

Breast cancer is a common but heterogeneous disease characterized by several biologic features, including tumor grade, hormone receptor status, human epidermal growth factor receptor 2 status, and gene expression assays. These biologic and genomic features drive treatment decisions. In the advanced disease setting, inter- and intrapatient tumor heterogeneity is increasingly recognized as a challenge for optimizing treatment. Recent evidence and the recent approval of novel radiopharmaceuticals have increased recognition and acceptance of the potential of molecular imaging as a biomarker to impact and guide management decisions for advanced breast cancer., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Accurate lymph node size estimation is critical for staging cancer patients, initial therapeutic management, and assessing response to therapy. Current standard practice for quantifying lymph node size is based on a variety of criteria that use uni-directional or bi-directional measurements. Segmentation in 3D can provide more accurate evaluations of the lymph node size. Fully convolutional neural networks (FCNs) have achieved state-of-the-art results in segmentation for numerous medical imaging applications, including lymph node segmentation. Adoption of deep learning segmentation models in clinical trials often faces numerous challenges. These include lack of pixel-level ground truth annotations for training, generalizability of the models on unseen test domains due to the heterogeneity of test cases and variation of imaging parameters. In this paper, we studied and evaluated the performance of lymph node segmentation models on a dataset that was completely independent of the one used to create the models. We analyzed the generalizability of the models in the face of a heterogeneous dataset and assessed the potential effects of different disease conditions and imaging parameters. Furthermore, we systematically compared fully-supervised and weakly-supervised methods in this context. We evaluated the proposed methods using an independent dataset comprising 806 mediastinal lymph nodes from 540 unique patients. The results show that performance achieved on the independent test set is comparable to that on the training set. Furthermore, neither the underlying disease nor the heterogeneous imaging parameters impacted the performance of the models. Finally, the results indicate that our weakly-supervised method attains 90%- 91% of the performance achieved by the fully supervised training., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gordon Harris reports financial support was provided by National Institutes of Health. Gordon Harris reports a relationship with Novometrics, LLC that includes: equity or stocks. Gordon Harris reports a relationship with IQ Medical Imaging, LLC that includes: equity or stocks. Gordon Harris reports a relationship with Fovia, Inc that includes: consulting or advisory. Erik Ziegler reports a relationship with Radical Imaging LLC that includes: consulting or advisory. Trinity Urban is a current employee of Clario, formerly Bioclinica., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in of 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, P < .001) and inferior overall survival (52% vs 68%, P = .05). The sensitivity and specificity of ASC MRD positivity for progression and death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in multivariable analysis (hazard ratio [HR], 3.7; P < .001). Post-ASCT surveillance MRD testing of plasma, but not PBMC samples, reliably identified patients with an impending relapse. A positive plasma MRD result was associated with inferior PFS (HR, 3.0; P = .016) in a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range, 0-518 days). In conclusion, the detection of MRD in ASC samples is associated with a very high risk of relapse, justifying alternative treatment strategies or trials of novel consolidation options in these patients. Furthermore, post-ASCT MRD monitoring may facilitate the evaluation of the early initiation of treatment at molecular relapse. This trial has been registered at www.clinicaltrials.gov as #NCT02362997., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In a prospective clinical trial, [ 18 F]fluoro-5α-dihydrotestosterone ([ 18 F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [ 18 F]FDHT in women. Methods: [ 18 F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [ 18 F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of 18 F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [ 18 F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [ 18 F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P < 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P < 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P < 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [ 18 F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice., (© 2023. The Author(s).)

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS ( P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET ( P < 0.001) and progression of disease within 24 months (POD24) ( P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS ( P < 0.001) or ΔSUVmax75% ( P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Introduction: 177 Lu-vipivotide tetraxetan is a radiopharmaceutical that selectively targets prostate-specific membrane antigen (PSMA) and delivers beta-radiations to kill prostate cancer cells., Areas Covered: Extensive experience outside the United States as well as randomized phase II and phase III data demonstrate that 177 Lu-vipivotide tetraxetan is a safe, generally well tolerated, and effective therapy for men with mCRPC. 177 Lu-vipivotide tetraxetan was approved by the FDA in March 2022 for the treatment of PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition and taxane-based chemotherapy based on the results of the VISION trial., Expert Opinion: This review discusses the development and studies leading to the approval of 177 Lu-vipivotide tetraxetan. In all, 177 Lu-vipivotide tetraxetan is an exciting new tool in the arsenal for men with mCRPC after novel androgen pathway inhibitors and at least one taxane chemotherapy. Optimal selection of patients, sequencing of 177 Lu-vipivotide tetraxetan with the other agents available to treat mCRPC, and the use of dosimetry are current areas of interest with great potential and opportunities for further individual patient optimization using the tools of theranostics.

Malignant pheochromocytomas (PHEOs)/paragangliomas (PGLs) are rare tumors for which clinical outcomes remain poorly defined and therapeutic options are limited. Approximately 27% carry pathogenic germline succinate dehydrogenase (SDHx) mutations; the presence of such mutations has been correlated with response to temozolomide (TMZ). We aimed to investigate the association between germline mutations in SDHx and response to TMZ. We retrospectively identified patients with metastatic malignant PHEO/PGLs treated with TMZ- based chemotherapy at Dana-Farber Cancer Institute between 2003 and 2020. The correlation between response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and PET Response Criteria in Solid Tumors (PERCIST) and the presence of SDHx mutations in the germline and tumor was evaluated. Nineteen patients received TMZ. Seventeen underwent germline assessment: 9 (53%) carried a pathogenic SDHx germline mutation. Fifteen patients were evaluable for response by RECIST 1.1: 6 (40%) partial response, 4 (27%) stable disease, and 5 (33%) progressive disease. Overall median progression-free survival was 2.2 years. Three-year overall survival (OS) was 58%. Median PFS was 1.3 years and 5.5 years for carriers and non-carriers, respectively and OS was 1.5 years and not estimable for carriers and non-carriers, respectively. The response by PERCIST criteria in nine patients correlated with the RECIST 1.1 assessment. Our series represents one of the largest analyses of patients with malignant PHEOs/PGLs treated with TMZ who have available germline data. The incidence of pathogenic germline SDHx mutations was similar to what has been previously published, though our analysis suggests that there may be a limited association between response to TMZ and pathogenic germline SDHx mutations.

Rationale and Objectives: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability., Materials and Methods: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy., Results: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR., Conclusion: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Most breast cancers express androgen receptors (ARs). This prospective imaging substudy explored imaging of ARs with 18 F-fluoro-5α-dihydrotestosterone ( 18 F-FDHT) PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024). Methods: Eleven postmenopausal women with estrogen receptor-positive MBC underwent 18 F-FDHT PET/CT at baseline and at 6 and 12 wk after starting SARM therapy. Abnormal tumor 18 F-FDHT uptake was quantified using SUV max AR status was determined from tumor biopsy specimens. 18 F-FDHT SUV max percentage change between scans was calculated. Best overall response was categorized as clinical benefit (nonprogressive disease) or progressive disease using RECIST 1.1. Results: The median baseline 18 F-FDHT SUV max was 4.1 (range, 1.4-5.9) for AR-positive tumors versus 2.3 (range, 1.5-3.2) for AR-negative tumors ( P  = 0.22). Quantitative AR expression and baseline 18 F-FDHT uptake were weakly correlated (Pearson ρ = 0.39, P  = 0.30). Seven participants with clinical benefit at 12 wk tended to have larger declines in 18 F-FDHT uptake than did those with progressive disease both at 6 wk after starting GTx-024 (median, -26.8% [range, -42.9% to -14.1%], vs. -3.7% [range,-31% to +29%], respectively; P  = 0.11) and at 12 wk after starting GTx-024 (median, -35.7% [range, -69.5% to -7.7%], vs. -20.1% [range, -26.6% to +56.5%], respectively; P  = 0.17). Conclusion: These hypothesis-generating data suggest that 18 F-FDHT PET/CT is worth further study as an imaging biomarker for evaluating the response of MBC to SARM therapy and reiterate the feasibility of including molecular imaging in multidisciplinary therapeutic trials., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The use of radiopharmaceutical therapies (RPTs) in the treatment of cancers is growing rapidly, with more agents becoming available for clinical use in last few years and many new RPTs being in development. Dosimetry assessment is critical for personalized RPT, insofar as administered activity should be assessed and optimized in order to maximize tumor-absorbed dose while keeping normal organs within defined safe dosages. However, many current clinical RPTs do not require patient-specific dosimetry based on current Food and Drug Administration-labeled approvals, and overall, dosimetry for RPT in clinical practice and trials is highly varied and underutilized. Several factors impede rigorous use of dosimetry, as compared with the more convenient and less resource-intensive practice of empiric dosing. We review various approaches to applying dosimetry for the assessment of activity in RPT and key clinical trials, the extent of dosimetry use, the relative pros and cons of dosimetry-based versus fixed activity, and practical limiting factors pertaining to current clinical practice., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: Dermal lymphatic invasion (DLI) with tumor emboli is a common pathologic characteristic of inflammatory breast cancer (IBC), although its presence is not required for diagnosis. We examined whether documented DLI on skin biopsy was associated with survival and time to recurrence or progression in IBC., Materials and Methods: A total of 340 women enrolled in the IBC Registry at Dana-Farber Cancer Institute between 1997 and 2019 were included in this study. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for associations of DLI and overall survival, time to locoregional recurrence/progression, and distant metastasis by stage at presentation., Results: DLI was detected in 215 (63.2%) of IBC cases overall. At disease presentation, IBC with DLI had a higher prevalence of de novo metastases (37.7% vs. 26.4%), breast skin ulceration (6.1% vs. 2.4%), and lymphovascular invasion within the breast parenchyma (52.9% vs. 25.5%) and a lower prevalence of palpable breast mass (48.2% vs. 70.6%) than IBC without DLI. Over a median follow-up of 2.0 years, 147 deaths occurred. DLI was not associated with survival or recurrence in multivariable models (all P ≥0.10). For example, among women with stage III disease, hazard ratios (95% confidence intervals) for DLI presence was 1.29 (0.77-2.15) for overall survival, 1.29 (0.56-3.00) for locoregional recurrence, and 1.71 (0.97-3.02) for distant metastasis., Conclusion: Although the extent of tumor emboli in dermal lymphatics may be associated with biological features of IBC, DLI was not an independent prognostic marker of clinical outcomes in this study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)