Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training. To overcome this limitation, this study explores semi-supervised approaches utilizing unlabeled data, specifically focusing on PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) obtained from two centers. We considered 2-[18F]FDG PET images of 292 patients PMBCL (n = 104) and DLBCL (n = 188) (n = 232 for training and validation, and n = 60 for external testing). We harnessed classical wisdom embedded in traditional segmentation methods, such as the fuzzy clustering loss function (FCM), to tailor the training strategy for a 3D U-Net model, incorporating both supervised and unsupervised learning approaches. Various supervision levels were explored, including fully supervised methods with labeled FCM and unified focal/Dice loss, unsupervised methods with robust FCM (RFCM) and Mumford-Shah (MS) loss, and semi-supervised methods combining FCM with supervised Dice loss (MS + Dice) or labeled FCM (RFCM + FCM). The unified loss function yielded higher Dice scores (0.73 ± 0.11; 95% CI 0.67-0.8) than Dice loss (p value < 0.01). Among the semi-supervised approaches, RFCM + αFCM (α = 0.3) showed the best performance, with Dice score of 0.68 ± 0.10 (95% CI 0.45-0.77), outperforming MS + αDice for any supervision level (any α) (p < 0.01). Another semi-supervised approach with MS + αDice (α = 0.2) achieved Dice score of 0.59 ± 0.09 (95% CI 0.44-0.76) surpassing other supervision levels (p < 0.01). Given the time-consuming nature of manual delineations and the inconsistencies they may introduce, semi-supervised approaches hold promise for automating medical imaging segmentation workflows.

TMTV-Net: fully automated total metabolic tumor volume segmentation in lymphoma PET/CT images - a multi-center generalizability analysis.

PURPOSE: Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. METHODS: Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was divided into 900 scans for development/validation/testing phases and 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. RESULTS: Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. CONCLUSION: TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions.

Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. RESULTS: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. CONCLUSION: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

Long-term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography and laboratory analyses every 6 months for 5 years. Radiological findings were categorized based on the Lugano classification as complete response (CR), partial response, stable disease (SD), or progressive disease. RESULTS: Initial treatment included observation (n=2), surgical resection (n=6), or systemic chemotherapy (n=34). Patients treated surgically had localized disease and achieved initial and long-term CR. Of the 34 patients who underwent chemotherapy, 30 achieved CR, 2 achieved SD, and 2 died. Overall and progression-free survival (PFS) rates were 93.9% and 54.3%, respectively. Multivariate analysis indicated that PFS was lower in patients with modified Ann Arbor stage III-IV lymphoma and those who did not achieve CR. CONCLUSIONS: Optimized treatment based on anatomical location, pulmonary function, and disease stage can improve long-term survival in patients with pulmonary MALT lymphoma.

Prognostic Value of FDG PET/CT in Patients with Nodal Peripheral T-Cell Lymphoma.

This study evaluated the prognostic significance of FDG PET/CT in patients with nodal peripheral T-cell lymphoma (PTCL). We retrospectively reviewed patients with histologically confirmed nodal PTCL who underwent FDG PET/CT at baseline, after three cycles of first-line chemotherapy (interim), and at the end of therapy. Response was assessed visually using the Deauville 5-point scale (D5PS); scores of 1, 2, and 3 were considered PET-negative, and scores of 4 and 5 were considered PET-positive. The associations between FDG PET/CT findings and survival were assessed using Cox regression analysis. A total of 79 patients (44 males and 35 females; median age 56 years) were included in this study. In response assessment, 17 (22%) had an interim PET-positive result and 10 (13%) had an end-of-therapy PET-positive result. During a median follow-up of 50 months, 37 patients (47%) presented with disease progression and 30 patients (38%) died. The estimated 5-year progression-free survival (PFS) and overall survival (OS) were 57% and 64%, respectively. An interim PET-positive result was the only significant indicator of PFS. Higher International Prognostic Index and end-of-therapy PET-positive result were significant independent prognostic factors of OS. Interim and end-of-therapy FDG PET/CT responses based on D5PS are meaningful in predicting the outcomes of patients with nodal PTCL.

Diagnosis, treatment, and prognosis of primary intraocular lymphoma: Single-center real-world clinical experience.

BACKGROUND: The diagnosis and management of primary intraocular lymphoma (PIOL) remain challenging. This study identified factors indicative of PIOL, described treatment outcomes, and determined modalities to prevent relapse. METHODS: We included 21 PIOL-diagnosed patients, seven via cytology, 12 via genetic evaluation, and two via interleukin (IL) level measurements, who underwent vitrectomy and received local intravitreal methotrexate (IV-MTX) injection. Clinical outcomes, including treatment response and relapse, were compared between patients receiving IV-MTX alone (n = 13) or IV-MTX with systemic high-dose methotrexate (HD-MTX) as prophylaxis (n = 8). RESULTS: Twelve ophthalmologic and eight central nervous system (CNS) relapse cases within a median of 20.3 and 11.6 months were shown, regardless of the treatment modalities, with a median progression-free survival of 21.3 (95% confidence interval, 9.5-36.7) months. There was no difference in demographic characteristics between the two groups, except with the poorer performance status in patients in the HD-MTX prophylaxis group. Furthermore, patients demonstrated rapid elevations in the vitreous fluid IL-10/IL-6 cytokine ratio before ophthalmologic and CNS relapse. Therefore, diagnosis should be based on clinical signs and assisted by vitrectomy, cytologic, molecular, and cytokine studies. CONCLUSION: For PIOL, aggressive systemic treatment equivalent to that of primary CNS lymphoma (PCNSL) is recommended because solely HD-MTX did not prevent or delay CNS relapse. To prevent PIOL relapse in the CNS efficiently, prospective trials with large numbers of patients and advanced therapeutic regimens are necessary. Furthermore, regular clinical follow-up is crucial, and the IL-10/IL-6 ratio can help evaluate relapse promptly.

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience.

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1-2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The "watch-and-wait" strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [177Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial.

[177Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [177Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.8 GBq, 3.7 GBq, 4.6 GBq, and 5.6 GBq. [177Lu]Ludotadipep was administered via venous injection, and patients were hospitalized for three days to monitor for any adverse effects. Serum PSA levels were followed up at weeks 1, 2, 3, 4, 6, 8, and 12, and PSMA PET/CT with [18F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [177Lu]Ludotadipep administration. Among the 29 subjects who received [177Lu]Ludotadipep, 36 treatment emergent adverse events (TEAEs) occurred in 17 subjects (58.6%) and 4 adverse drug reactions (ADRs) in 3 subjects (10.3%). Of the total 24 subjects who had full 12-week follow-up data, 16 (66.7%) showed decrease in PSA of any magnitude, and 9 (37.5%) showed a decrease in PSA by 50% or greater. A total of 5 of the 24 patients (20.8%) showed disease progression (PSA increase of 25% or higher from the baseline) at the 12th week following single dose of [177Lu]Ludotadipep. These data thus far suggest that [177Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments.

18 F-Flutemetamol PET/CT for Transthyretin Amyloid Cardiomyopathy : Timing Matters.

ABSTRACT: We report 18 F-flutemetamol PET/CT finding in an 88-year-old man with cognitive impairment and transthyretin amyloid cardiomyopathy. Early phase PET/CT images showed significantly increased myocardial uptake, but there was no myocardial uptake in delayed phase PET/CT images. A dual-time-point amyloid PET/CT imaging may be helpful to diagnose and differentiate subtypes of amyloid cardiomyopathy in patients with suspected cardiac amyloidosis.

AL-Type Amyloidosis Involving Stomach and Lungs in 99m Tc-DPD Bone Scan.

ABSTRACT: Systemic AL (amyloid light-chain) amyloidosis is a relatively rare disease. 99m Tc-DPD (3,3-diphosphono-1,2-pyrophosphate) bone scan is a highly sensitive diagnostic tool for cardiac amyloidosis of ATTR (transthyretin) type. In AL amyloidosis, there have been some previous reports of extracardiac DPD uptake in liver, kidney, and spleen, but not in stomach. We present 99m Tc-DPD bone scan images of AL-type amyloidosis involving stomach and lung.

Long-Term Clinical Outcomes in Treatment-Naïve Patients With Orbital Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma: A Single-Center Study.

Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (OAML) is the most common type of ocular lymphoma with a higher prevalence in Asia than in Western countries. OAML represents 1%-2% of all non-Hodgkin's lymphoma, 5%-15% of extranodal lymphomas, and approximately 55% of orbital malignancies. "Watch and wait" after biopsy or surgical resection, radiation therapy, and systemic treatment, including antibiotics administration and chemotherapy with various combinations of regimens can be considered for OAML treatment. Radiotherapy is adapted for limited-stage disease with excellent clinical outcomes of 85-100% complete remission and relatively superior local control efficacy and treatment duration. In contrast, chemotherapy has rarely been tested as frontline therapy. Nonetheless, several studies have reported a favorable response and long duration of progression-free survival using chemotherapy adaptations. When the disease involves both eyes or spreads beyond the conjunctiva, the risk of recurrence increases and limited-stage OAML has a recurrence rate of approximately 25% following radiotherapy only. Therefore, although recent consensus in the literature is that patients with limited-stage OAML recommended treating with radiation, physicians may choose the treatment modality not only by its efficiency but also by its adverse events profile and patients' well-being. Herein, we present a large single-center study on OAML that included 292 patients who were followed up for up to 237 months. We collected and analyzed real-world data focusing on treatment outcomes and the role of radiotherapy as frontline therapy, and aimed to compare outcomes and complication profiles of chemotherapy, especially in limited-stage OAML, to identify an optimal treatment strategy.

Comparison of FDG PET/CT and Bone Marrow Biopsy Results in Patients with Diffuse Large B Cell Lymphoma with Subgroup Analysis of PET Radiomics.

Whether FDG PET/CT can replace bone marrow biopsy (BMBx) is undecided in patients with diffuse large B cell lymphoma (DLBCL). We compared the visual PET findings and PET radiomic features, with BMBx results. A total of 328 patients were included; 269 (82%) were PET-negative and 59 (18%) were PET-positive for bone lesions on visual assessment. A fair degree of agreement was present between PET and BMBx findings (ĸ = 0.362, p < 0.001). Bone involvement on PET/CT lead to stage IV in 12 patients, despite no other evidence of extranodal lesion. Of 35 discordant PET-positive and BMBx-negative cases, 22 (63%) had discrete bone uptake on PET/CT. A total of 144 patients were eligible for radiomic analysis, and two grey-level zone-length matrix derived parameters obtained from the iliac crests showed a trend for higher values in the BMBx-positive group compared to the BMBx-negative group (mean 436.6 ± 449.0 versus 227.2 ± 137.8, unadjusted p = 0.037 for high grey-level zone emphasis; mean 308.8 ± 394.4 versus 135.7 ± 97.2, unadjusted p = 0.048 for short-zone high grey-level emphasis), but statistical significance was not found after multiple comparison correction. Visual FDG PET/CT assessment and BMBx results were discordant in 17% of patients with newly diagnosed DLBCL, and the two tests are complementary in the evaluation of bone involvement.

Comparison of early F-18 Florbetaben PET/CT to Tc-99m ECD SPECT using voxel, regional, and network analysis.

This study aimed to validate early-phase F-18 Florbetaben positron emission tomography (eFBB PET) as a brain perfusion test and determine the optimal reference region. A total of 27 patients with early Parkinson's disease with Tc-99m ethyl cysteinate dimer single photon emission tomography (ECD SPECT) and FBB PET were included. Six reference regions, including whole brain (GN), pons, central white matter (CWM), whole cerebellum (WC), WC with brain stem (WC + B), and cerebellar grey matter (CG), were applied to obtain SUVR using cortex volume-of-interest (VOI). Reference regions of WC (r 0.886), WC + B (r 0.897), and CG (r 0.904) had highest correlation values of cortex-VOI SUVR between both perfusion images (all p < 0.001). Early-phase FBB PET had a significant linear correlation of CG-normalized SUVR of the cortex, basal ganglia, thalamus, and midbrain with ECD SPECT in voxel-wise analysis (FDR adjusted-p < 0.05). Early-phase FBB PET extracts more ICNS than ECD SPECT, as 9 ICNS and 4 ICNs, respectively. Both eFBB PET and ECD SPECT well discriminated PD from DLB (Area-under-curve of receiver-operating-characteristics, 0.911 for eFBB PET, 0.922 for ECD SPECT). Our findings suggest that eFBB PET is a reliable perfusion test based on a high correlation with ECD SPECT using cerebellum-based normalization methods.

One Versus Up-to-5 Lesion Measurements for Response Assessment by PERCIST in Patients with Lung Cancer.

PURPOSE: The optimal number of lesions to measure for response assessment from fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is not validated for lung cancer. We compared 1 lesion and up-to-5 lesion measurements for response assessment in lung cancer per PET Response Criteria in Solid Tumors (PERCIST). METHODS: Patients with lung cancer with pre- and post-treatment PET/CT images were included. The standard uptake value corrected for lean body mass (SULpeak) of up-to-5 hottest target lesions was measured at each time point. The percent changes of SULpeak of the single hottest lesion and the sum of up-to-5 hottest lesions were computed. Pearson correlation coefficient evaluated the strength of association between the percent changes of SULpeak values from the 1 lesion and up-to-5 lesion analyses. Response categories were complete metabolic response (CMR) with no perceptible lesion; partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD) using the threshold of 30% and 0.8 unit change in SULpeak; and unequivocal new lesion meant PMD. The concordance for response categorization was assessed by kappa statistics. RESULTS: A total of 40 patients (25 non-small cell lung cancer; 15 small cell lung cancer) were analyzed, all with 18F-FDG-avid lung cancer. Average of 3 target lesions were measured for up-to-5 lesion analysis. Pearson's r was 0.74 (P < 0.001) and increased to 0.96 (P < 0.001) when two outliers were excluded. Response categorization with 1 lesion and up-to-5 lesion analyses was concordant in 37 patients (92.5%, weighted kappa = 0.89). CONCLUSION: Analyzing 1 lesion and up-to-5 lesions for response assessment by PERCIST showed high concordance in patients with lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13139-021-00697-4.

Emerging Role of Consolidative Radiotherapy After Complete Remission Following R-CHOP Immunochemotherapy in Stage III-IV Diffuse Large B-Cell Lymphoma: A Single Institutional and Case-Matched Control Study.

PURPOSE: The role of consolidative radiotherapy (RT) after complete-remission (CR) following rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in advanced-stage diffuse large B-cell lymphoma (DLBCL) remains unclear. We retrospectively analyzed the survival outcomes and patterns of failure with our institutional experience. MATERIAL AND METHODS: Between 2009 and 2018, 206 patients with stage III-IV DLBCL achieved CR after receiving R-CHOP. Propensity-score matching was used to analyze the role of consolidative RT. The consolidative RT group (n = 34) and the R-CHOP alone group (n = 68) were matched at a 1:2 ratio. After propensity-score matching, 102 patients were analyzed. RESULTS: With a median follow-up of 39.7 months, 26 patients (25.5%) showed local recurrence. Only one patient failed at the previous RT field. RT was delivered to bulky sites, head and neck lesions, testes, and bone with median dose of 30.6 Gy. The most common site of failure was head and neck lesions followed by bulky sites. The 5-year overall survival (OS), progression-free survival (PFS), and isolated-local recurrence free survival (LRFS) were 73.5, 64.0, and 79.9%. In univariate and multivariate analysis, bone marrow involvement and consolidative RT were associated with isolated LRFS (p = 0.006 and 0.032) significantly. CONCLUSION: Consolidative RT improved isolated local control. Based on the pattern of failure, we carefully suggest to radiate on initially involved bulky sites or head and neck lesions. Further studies need to be done to find out the optimal radiation dose and selection of RT site.

Prognostic value of tumor metabolic imaging phenotype by FDG PET radiomics in HNSCC.

OBJECTIVE: Tumor metabolic phenotype can be assessed with integrated image pattern analysis of 18F-fluoro-deoxy-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT), called radiomics. This study was performed to assess the prognostic value of radiomics PET parameters in head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 18F-fluoro-deoxy-glucose (FDG) PET/CT data of 215 patients from HNSCC collection free database in The Cancer Imaging Archive (TCIA), and 122 patients in Seoul St. Mary's Hospital with baseline FDG PET/CT for locally advanced HNSCC were reviewed. Data from TCIA database were used as a training cohort, and data from Seoul St. Mary's Hospital as a validation cohort. With the training cohort, primary tumors were segmented by Nestles' adaptive thresholding method. Segmental tumors in PET images were preprocessed using relative resampling of 64 bins. Forty-two PET parameters, including conventional parameters and texture parameters, were measured. Binary groups of homogeneous imaging phenotypes, clustered by K-means method, were compared for overall survival (OS) and disease-free survival (DFS) by log-rank test. Selected individual radiomics parameters were tested along with clinical factors, including age and sex, by Cox-regression test for OS and DFS, and the significant parameters were tested with multivariate analysis. Significant parameters on multivariate analysis were again tested with multivariate analysis in the validation cohort. RESULTS: A total of 119 patients, 70 from training, and 49 from validation cohort, were included in the study. The median follow-up period was 62 and 52 months for the training and the validation cohort, respectively. In the training cohort. binary groups with different metabolic radiomics phenotypes showed significant difference in OS (p = 0.036), and borderline difference in DFS (p = 0.086). Gray-Level Non-Uniformity for zone (GLNUGLZLM) was the most significant prognostic factor for both OS (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.4-7.3, p = 0.008) and DFS (HR 4.5, CI 1.3-16, p = 0.020). Multivariate analysis revealed GLNUGLZLM as an independent prognostic factor for OS (HR 3.7, 95% CI 1.1-7.5, p = 0.032). GLNUGLZLM remained as an independent prognostic factor in the validation cohort (HR 14.8. 95% CI 3.3-66, p < 0.001). CONCLUSIONS: Baseline FDG PET radiomics contain risk information for survival prognosis in HNSCC patients. The metabolic heterogeneity parameter, GLNUGLZLM, may assist clinicians in patient risk assessment as a feasible prognostic factor.

Quantitation of cancer treatment response by 2-[18F]FDG PET/CT: multi-center assessment of measurement variability using AUTO-PERCIST™.

BACKGROUND: The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SULpeak) to determine [18F]FDG PET quantitative parameters. METHODS: Paired pre- and post-treatment [18F]FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (readreference), whereas the 12 other readers were blinded to history but had access to the correlative images. Auto-PERCIST™ was set up to first automatically identify the liver and compute the threshold for tumor measurability (1.5 × liver mean) + (2 × liver standard deviation [SD]) and then detect all sites with SULpeak greater than the threshold. Next, the readers selected sites they believed to represent tumor lesions. The main performance metric assessed was the percent change in the SULpeak (%ΔSULpeak) of the hottest tumor identified on the baseline and follow-up images. RESULTS: The intra-class correlation coefficient (ICC) for the %ΔSULpeak of the hottest tumor was 0.87 (95%CI: [0.78, 0.92]) when all reads were included (n = 297). Including only the measurements that selected the same target tumor as the readreference (n = 224), the ICC for %ΔSULpeak was 1.00 (95%CI: [1.00, 1.00]). The Krippendorff alpha coefficient for response (complete or partial metabolic response, versus stable or progressive metabolic disease on PET Response Criteria in Solid Tumors 1.0) was 0.91 for all reads (n = 380) and 1.00 including for reads with the same target tumor selection (n = 270). CONCLUSION: Quantitative tumor [18F]FDG SULpeak changes measured across multiple global sites and readers utilizing Auto-PERCIST™ show very high correlation. Harmonization of methods to single software, Auto-PERCIST™, resulted in virtually identical extraction of quantitative tumor response data from [18F]FDG PET images when the readers select the same target tumor.

FDG PET/CT Findings of Castleman Disease Assessed by Histologic Subtypes and Compared with Laboratory Findings.

Castleman disease (CD) is a relatively rare lymphoproliferative disorder and the pathophysiology of the subtypes are incompletely understood. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrates the metabolic activity of inflammatory and tumorous conditions. The FDG uptake intensity and sites of involved lesions on FDG PET/CT were assessed by histologic subtypes, and compared to the patient's hemoglobin, platelet, albumin, and high-sensitivity C-reactive protein (hs-CRP) levels. In total, 60 PET/CT images of 44 consecutive CD patients were included: 4 (9%) unicentric and 40 (91%) multicentric; 21 (48%) hyaline vascular subtype, 16 (36%) plasma cell, and 7 (16%) mixed or unclassified. The maximum standardized uptake value (SUVmax) and tumor-to-liver (T/L) ratio of involved lymph nodes (LNs) were 5.3 ± 2.4 (range, 1.6-11.5) and 2.8 ± 1.6 (range, 1.1-9.6), respectively, with no significant difference between the histologic subtypes. Higher number of involved LN stations and presence of extra-nodal involvement on FDG PET/CT were associated with thrombocytopenia, hypoalbuminemia, and elevated hs-CRP levels (p values < 0.05). FDG-avidity was not different by histologic subtypes and did not correlate with laboratory findings. However, the extent of nodal and extra-nodal involvement as noted on FDG PET/CT was significantly associated with abnormal laboratory findings in patients with CD.

Early Interim Chemotherapy Response Evaluation by F-18 FDG PET/CT in Diffuse Large B Cell Lymphoma.

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after one cycle of standard chemotherapy in patients with diffuse large B cell lymphoma (DLBCL) was assessed. Prospectively enrolled 51 patients had four PET/CT studies using the same protocol and system: at baseline and after one, three, and six cycles of chemotherapy (PET0, PET1, PET3, PET6). The PET1 and PET6 Deauville five-point score (D5PS) agreed in 60.8%, while PET3 and PET6 D5PS agreed in 90.2%. The absolute and percent changes of peak standard uptake value corrected for lean body mass (SULpeak) compared to baseline were significantly different between PET1 and PET3 (p = 0.001, p < 0.001) and PET1 and PET6 (p = 0.002, p = 0.001), but not between PET3 and PET6 (p = 0.276, p = 0.181). The absolute SULpeak from PET1 predicted treatment failure with accuracy of 78.4% (area under the curve 0.73, p = 0.023). D5PS, SULpeak, and metabolic tumor volume (MTV) were not statistically different between responders versus non-responders, or the one year disease-free versus relapse groups. D5PS and PERCIST responses showed 100% agreement at end-of-therapy. In conclusion, the responses after three and six cycles of therapy showed high degree of agreement. D5PS or MTV after one cycle of chemotherapy could not predict response or one-year disease-free status, but the SULpeak from PET1 was associated with response to first line therapy in DLBCL. Deauville and PERCIST criteria show high concordance.

Spontaneous Remission and Concomitant Progression in a Patient with DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Although DLBCL can be cured in more than half of all patients, up to 50% of patients become refractory to initial treatment or relapse after complete remission. We present a case of complete spontaneous remission of some tumors and concomitant newly developed tumors observed in a patient with relapsed DLBCL. Spontaneous remission of lymphoma without treatment is a rare phenomenon and can occur at baseline as well as in relapsed DLBCL. However, most patients who initially experience spontaneous remission later develop relapse. Thus, careful follow-up is required, and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) allows monitoring of multiple lesions.