Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Patients Using a Longitudinally-Aware Segmentation Network.

Purpose: Automatic quantification of longitudinal changes in PET scans for lymphoma patients has proven challenging, as residual disease in interim-therapy scans is often subtle and difficult to detect. Our goal was to develop a longitudinally-aware segmentation network (LAS-Net) that can quantify serial PET/CT images for pediatric Hodgkin lymphoma patients. Materials and Methods: This retrospective study included baseline (PET1) and interim (PET2) PET/CT images from 297 patients enrolled in two Children's Oncology Group clinical trials (AHOD1331 and AHOD0831). LAS-Net incorporates longitudinal cross-attention, allowing relevant features from PET1 to inform the analysis of PET2. Model performance was evaluated using Dice coefficients for PET1 and detection F1 scores for PET2. Additionally, we extracted and compared quantitative PET metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in PET1, as well as qPET and ΔSUVmax in PET2, against physician measurements. We quantified their agreement using Spearman's ρ correlations and employed bootstrap resampling for statistical analysis. Results: LAS-Net detected residual lymphoma in PET2 with an F1 score of 0.606 (precision/recall: 0.615/0.600), outperforming all comparator methods (P<0.01). For baseline segmentation, LAS-Net achieved a mean Dice score of 0.772. In PET quantification, LAS-Net's measurements of qPET, ΔSUVmax, MTV and TLG were strongly correlated with physician measurements, with Spearman's ρ of 0.78, 0.80, 0.93 and 0.96, respectively. The performance remained high, with a slight decrease, in an external testing cohort. Conclusion: LAS-Net achieved high performance in quantifying PET metrics across serial scans, highlighting the value of longitudinal awareness in evaluating multi-time-point imaging datasets.

Personalized Impression Generation for PET Reports Using Large Language Models.

Large language models (LLMs) have shown promise in accelerating radiology reporting by summarizing clinical findings into impressions. However, automatic impression generation for whole-body PET reports presents unique challenges and has received little attention. Our study aimed to evaluate whether LLMs can create clinically useful impressions for PET reporting. To this end, we fine-tuned twelve open-source language models on a corpus of 37,370 retrospective PET reports collected from our institution. All models were trained using the teacher-forcing algorithm, with the report findings and patient information as input and the original clinical impressions as reference. An extra input token encoded the reading physician's identity, allowing models to learn physician-specific reporting styles. To compare the performances of different models, we computed various automatic evaluation metrics and benchmarked them against physician preferences, ultimately selecting PEGASUS as the top LLM. To evaluate its clinical utility, three nuclear medicine physicians assessed the PEGASUS-generated impressions and original clinical impressions across 6 quality dimensions (3-point scales) and an overall utility score (5-point scale). Each physician reviewed 12 of their own reports and 12 reports from other physicians. When physicians assessed LLM impressions generated in their own style, 89% were considered clinically acceptable, with a mean utility score of 4.08/5. On average, physicians rated these personalized impressions as comparable in overall utility to the impressions dictated by other physicians (4.03, P = 0.41). In summary, our study demonstrated that personalized impressions generated by PEGASUS were clinically useful in most cases, highlighting its potential to expedite PET reporting by automatically drafting impressions.

Voxel-Level Dosimetry for Combined Iodine 131 Radiopharmaceutical Therapy and External Beam Radiation Therapy Treatment Paradigms for Head and Neck Cancer.

PURPOSE: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiation therapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo-based dosimetry from the 2 radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase 1 clinical trial combining EBRT and RPT. METHODS AND MATERIALS: Serial single-photon emission computed tomography (SPECT)/computed tomography (CT) patient scans were performed at approximately 24, 48, 72, and 168 hours postinjection of 577.2 MBq/m2 (15.6 mCi/m2) CLR 131, an iodine 131-containing RPT agent. Using RayStation, clinical EBRT treatment plans were created with a treatment planning CT (TPCT). SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer software and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using RAPID, a GEANT4-based RPT dosimetry platform. Radiobiological metrics (biologically effective dose and equivalent dose in 2-Gy fractions) were used to combine the 2 radiation modalities. RESULTS: The DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT images, with a maximum mean absorbed dose difference of -11.2%. Based on the RPT absorbed dose calculations, 2 to 4 EBRT fractions were removed from patient EBRT treatments. For the combined treatment, the absorbed dose to target volumes ranged from 57.14 to 75.02 Gy. When partial volume corrections were included, the mean equivalent dose in 2-Gy fractions to the planning target volume from EBRT + RPT differed -3.11% to 1.40% compared with EBRT alone. CONCLUSIONS: This work demonstrates the clinical feasibility of performing combined EBRT + RPT dosimetry on TPCT scans. Dosimetry guides treatment decisions for EBRT, and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space.

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.

Domain-adapted Large Language Models for Classifying Nuclear Medicine Reports.

Purpose: To evaluate the impact of domain adaptation on the performance of language models in predicting five-point Deauville scores on the basis of clinical fluorine 18 fluorodeoxyglucose PET/CT reports. Materials and Methods: The authors retrospectively retrieved 4542 text reports and images for fluorodeoxyglucose PET/CT lymphoma examinations from 2008 to 2018 in the University of Wisconsin-Madison institutional clinical imaging database. Of these total reports, 1664 had Deauville scores that were extracted from the reports and served as training labels. The bidirectional encoder representations from transformers (BERT) model and initialized BERT models BioClinicalBERT, RadBERT, and RoBERTa were adapted to the nuclear medicine domain by pretraining using masked language modeling. These domain-adapted models were then compared with the non-domain-adapted versions on the task of five-point Deauville score prediction. The language models were compared against vision models, multimodal vision-language models, and a nuclear medicine physician, with sevenfold Monte Carlo cross-validation. Means and SDs for accuracy are reported, with P values from paired t testing. Results: Domain adaptation improved the performance of all language models (P = .01). For example, BERT improved from 61.3% ± 2.9 (SD) five-class accuracy to 65.7% ± 2.2 (P = .01) following domain adaptation. Domain-adapted RoBERTa (named DA RoBERTa) performed best, achieving 77.4% ± 3.4 five-class accuracy; this model performed similarly to its multimodal counterpart (named Multimodal DA RoBERTa) (77.2% ± 3.2) and outperformed the best vision-only model (48.1% ± 3.5, P ≤ .001). A physician given the task on a subset of the data had a five-class accuracy of 66%. Conclusion: Domain adaptation improved the performance of large language models in predicting Deauville scores in PET/CT reports.Keywords Lymphoma, PET, PET/CT, Transfer Learning, Unsupervised Learning, Convolutional Neural Network (CNN), Nuclear Medicine, Deauville, Natural Language Processing, Multimodal Learning, Artificial Intelligence, Machine Learning, Language Modeling Supplemental material is available for this article. © RSNA, 2023See also the commentary by Abajian in this issue.

Automatic Personalized Impression Generation for PET Reports Using Large Language Models.

Purpose: To determine if fine-tuned large language models (LLMs) can generate accurate, personalized impressions for whole-body PET reports. Materials and Methods: Twelve language models were trained on a corpus of PET reports using the teacher-forcing algorithm, with the report findings as input and the clinical impressions as reference. An extra input token encodes the reading physician's identity, allowing models to learn physician-specific reporting styles. Our corpus comprised 37,370 retrospective PET reports collected from our institution between 2010 and 2022. To identify the best LLM, 30 evaluation metrics were benchmarked against quality scores from two nuclear medicine (NM) physicians, with the most aligned metrics selecting the model for expert evaluation. In a subset of data, model-generated impressions and original clinical impressions were assessed by three NM physicians according to 6 quality dimensions (3-point scale) and an overall utility score (5-point scale). Each physician reviewed 12 of their own reports and 12 reports from other physicians. Bootstrap resampling was used for statistical analysis. Results: Of all evaluation metrics, domain-adapted BARTScore and PEGASUSScore showed the highest Spearman's ρ correlations (ρ=0.568 and 0.563) with physician preferences. Based on these metrics, the fine-tuned PEGASUS model was selected as the top LLM. When physicians reviewed PEGASUS-generated impressions in their own style, 89% were considered clinically acceptable, with a mean utility score of 4.08 out of 5. Physicians rated these personalized impressions as comparable in overall utility to the impressions dictated by other physicians (4.03, P=0.41). Conclusion: Personalized impressions generated by PEGASUS were clinically useful, highlighting its potential to expedite PET reporting.

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer.

OBJECTIVES: Ovarian cancer is the most lethal cancer and future research needs to focus on the early detection and exploration of new therapeutic agents. The objectives of this proof-of-concept study are to assess the feasibility of PSMA 18F-DCFPyl PET/MR imaging for detecting ovarian cancer and to evaluate the PSMA distribution in patients with and without ovarian cancer. METHODS: This prospective pilot proof-of-concept study in patients with and without ovarian cancers occurred between October 2017 and January 2020. Patients were recruited from gynecologic oncology or hereditary ovarian cancer clinics, and underwent surgical removal of the uterus and ovaries for gynecologic indications. PSMA 18F-DCFPyl PET/MRI was obtained prior to standard of care surgery. RESULTS: Fourteen patients were scanned: four patients with normal ovaries, six patients with benign ovarian lesions, and four patients with malignant ovarian lesions. Tracer uptake in normal ovaries (SUVmax = 2.8 ± 0.4) was greater than blood pool (SUVmax = 1.8 ± 0.5, p < 0.0001). Tracer uptake in benign ovarian lesions (2.2 ± 1.0) did not differ significantly from blood pool (p = 0.331). Tracer uptake in ovarian cancer (SUVmax = 7.8 ± 3.8) was greater than blood pool (p < 0.0001), normal ovaries (p = 0.0014), and benign ovarian lesions (p = 0.005). CONCLUSION: PET/MR imaging detected PSMA uptake in ovarian cancer, with little to no uptake in benign ovarian findings. These results are encouraging and further studies in a larger patient cohort would be useful to help determine the extent and heterogeneity of PSMA uptake in ovarian cancer patients.

18F-FDG PET/CT in the Management of Osteosarcoma.

Osteosarcoma is the most common type of primary malignant bone tumor. 18F-FDG PET/CT is useful for staging, detecting recurrence, monitoring response to neoadjuvant chemotherapy, and predicting prognosis. Here, we review the clinical aspects of osteosarcoma management and assess the role of 18F-FDG PET/CT, in particular with regard to pediatric and young adult patients.

Prognostic value of chest x-ray- and CT-defined large mediastinal adenopathy in high-risk pediatric Hodgkin lymphoma: A report from the Children's Oncology Group Study AHOD0831.

PURPOSE/OBJECTIVE: We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL). MATERIALS/METHODS: Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MRCXR ) > 1/3; (ii) mediastinal mass ratio on CT (MRCT ) > 1/3; (iii) mediastinal mass volume on CT (MVCT ) > 200 mL; (iv) normalized mediastinal mass volume (MVCT /thoracic diameter [TD]) > 1 mL/mm; (v) mediastinal mass diameter on CT (MDCT ) > 10 cm; and (vi) normalized mediastinal mass diameter (MDCT /TD) > 1/3. RESULTS: Median age at diagnosis was 15.8 years (range: 5.2-21.3 years). In patients with a slow early response (SER) to chemotherapy, MVCT  > 200 mL, MDCT  > 10 cm, and MDCT /TD > 1/3 were associated with worse relapse-free survival (RFS) on MVA, while MRCXR  > 1/3, MRCT  > 1/3, and MVCT /TD > 1 mL/mm trended toward worse RFS; MDCT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MDCT /TD > 1/3 versus ≤1/3 on MVA (p = .02). CONCLUSION: LMA according to MVCT  > 200 mL, MDCT  > 10 cm, and MDCT /TD > 1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MDCT /TD > 1/3 appears to be the strongest predictor of inferior RFS.

Using 18F-DCFPyL Prostate-Specific Membrane Antigen-Directed Positron Emission Tomography/Magnetic Resonance Imaging to Define Intraprostatic Boosts for Prostate Stereotactic Body Radiation Therapy.

Purpose: The recently reported FLAME trial demonstrated a biochemical disease-free survival benefit to using a focal intraprostatic boost to multiparametric magnetic resonance imaging (mpMRI)-identified lesions in men with localized prostate cancer treated with definitive radiation therapy. Prostate-specific membrane antigen (PSMA)-directed positron emission tomography (PET) may identify additional areas of disease. In this work, we investigated using both PSMA PET and mpMRI in planning focal intraprostatic boosts using stereotactic body radiation therapy (SBRT). Methods and Materials: We evaluated a cohort of patients (n = 13) with localized prostate cancer who were imaged with 2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-2-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL) PET/MRI on a prospective imaging trial before undergoing definitive therapy. The number of lesions concordant (overlapping) and discordant (no overlap) on PET and MRI was assessed. Overlap between concordant lesions was evaluated using the Dice and Jaccard similarity coefficients. Prostate SBRT plans were created fusing the PET/MRI imaging to computed tomography scans acquired the same day. Plans were created using only MRI-identified lesions, only PET-identified lesions, and the combined PET/MRI lesions. Coverage of the intraprostatic lesions and doses to the rectum and urethra were assessed for each of these plans. Results: The majority of lesions (21/39, 53.8%) were discordant between MRI and PET, with more lesions seen by PET alone (12) than MRI alone (9). Of lesions that were concordant between PET and MRI, there were still areas that did not overlap between scans (average Dice coefficient, 0.34). Prostate SBRT planning using all lesions to define a focal intraprostatic boost provided the best coverage of all lesions without compromising constraints on the rectum and urethra. Conclusions: Using both mpMRI and PSMA-directed PET may better identify all areas of gross disease within the prostate. Using both imaging modalities could improve the planning of focal intraprostatic boosts.

Assessment of 18F-DCFPyL PSMA PET/CT and PET/MR quantitative parameters for reference standard organs: Inter-reader, inter-modality, and inter-patient variability.

Prostate specific membrane antigen (PSMA)-based radiotracers have shown promise for prostate cancer assessment. Evaluation of quantitative variability and establishment of reference standards are important for optimal clinical and research utility. This work evaluates the variability of PSMA-based [18F]DCFPyL (PyL) PET quantitative reference standards. Consecutive eligible patients with biochemically recurrent prostate cancer were recruited for study participation from August 2016-October 2017. After PyL tracer injection, whole body PET/CT (wbPET/CT) was obtained with subsequent whole body PET/MR (wbPET/MR). Two readers independently created regions of interest (ROIs) including a 40% standardized uptake value (SUV) threshold ROI of the whole right parotid gland and separate spherical ROIs in the superior, mid, and inferior gland. Additional liver (right lobe) and blood pool spherical ROIs were defined. Bland-Altman analysis, including limits of agreement (LOA), as well as interquartile range (IQR) and coefficient of variance (CoV) was used. Twelve patients with prostate cancer were recruited (mean age, 61.8 yrs; range 54-72 years). One patient did not have wbPET/MR and was excluded. There was minimal inter-reader SUVmean variability (bias±LOA) for blood pool (-0.13±0.42; 0.01±0.41), liver (-0.55±0.82; -0.22±1.3), or whole parotid gland (-0.05±0.31; 0.08±0.24) for wbPET/CT and wbPET/MR, respectively. Greater inter-reader variability for the 1-cm parotid gland ROIs was present, for both wbPET/CT and wbPET/MR. Comparing wbPET/CT to the subsequently acquired wbPET/MR, blood pool had a slight decrease in SUVmean. The liver as well as parotid gland showed a slight increase in activity although the absolute bias only ranged from 0.45-1.28. The magnitude of inter-subject variability was higher for the parotid gland regardless of modality or reader. In conclusion, liver, blood pool, and whole parotid gland quantitation show promise as reliable reference normal organs for clinical/research PET applications. Variability with 1-cm parotid ROIs may limit its use.

Importance of Central Imaging Review in a Pediatric Hodgkin Lymphoma Trial Using Positron Emission Tomography Response Adapted Radiation Therapy.

PURPOSE: We investigated the effects of central review of the interim fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan response (iPET) assessment on treatment allocation in the risk-based, response-adapted, Children's Oncology Group study AHOD1331 (ClinicalTrials.gov identifier: NCT02166463) for pediatric patients with high-risk Hodgkin lymphoma. METHODS AND MATERIALS: Per protocol, after 2 cycles of systemic therapy, patients underwent iPET, with visual response assessment by 5-point Deauville score (DS) at their treating institution and a real-time central review, with the latter considered the reference standard. An area of disease with a DS of 1 to 3 was considered a rapid-responding lesion, whereas a DS of 4 to 5 was considered a slow-responding lesion (SRL). Patients with 1 or more SRLs were considered iPET positive, whereas patients with only rapid-responding lesions were considered iPET negative. We conducted a predefined exploratory evaluation of concordance in iPET response assessment between institutional and central reviews of 573 patients. The concordance rate was evaluated using the Cohen κ statistic (κ > 0.80 was considered very good agreement and κ > 0.60-0.80, good agreement). RESULTS: The concordance rate (514 of 573 [89.7%]) had a κ of 0.685 (95% CI, 0.610-0.759), consistent with good agreement. In terms of the direction of discordance, among the 126 patients who were considered iPET positive by institutional review, 38 (30.2%) were categorized as iPET negative by central review, preventing overtreatment with radiation therapy. Conversely, among the 447 patients who were considered iPET negative by institutional review, 21 patients (4.7%) were categorized as iPET positive by the central review and would have been undertreated without radiation therapy. CONCLUSIONS: Central review is integral to PET response-adapted clinical trials for children with Hodgkin lymphoma. Continued support of central imaging review and education about DS are needed.

Baseline metabolic tumour burden improves risk stratification in Hodgkin lymphoma: A Children's Oncology Group study.

The Children's Oncology Group AHOD0831 study used a positron emission tomography (PET) response-adapted approach in high-risk Hodgkin lymphoma, whereby slow early responders (SERs) received more intensive therapy than rapid early responders (RERs). We explored if baseline PET-based characteristics would improve risk stratification. Of 166 patients enrolled in the COG AHOD0831 study, 94 (57%) had baseline PET scans evaluable for quantitative analysis. For these patients, total body metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax ) and peak SUV (SUVpeak ) were obtained. MTV/TLG thresholds were an SUV of 2.5 (MTV2.5 /TLG2.5 ) and 40% of the tumour SUVmax (MTV40% /TLG40% ). TLG2.5 was associated with event-free survival (EFS) in the complete cohort (p = 0.04) and in RERs (p = 0.01), but not in SERs (p = 0.8). The Youden index cut-off for TLG2.5 was 1841. Four-year EFS was 92% for RER/TLG2.5  up to 1841, 60% for RER/TLG2.5  greater than 1841, 74% for SER/TLG2.5  up to 1841 and 79% for SER/TLG2.5  greater than 1841. Second EFS for RER/TLG2.5  up to 1841 was 100%. Thus, RERs with a low baseline TLG2.5 experienced excellent EFS with less intensive therapy, whereas RERs with a high baseline TLG2.5 experienced poor EFS. These findings suggest that patients with a high upfront tumour burden may benefit from intensified therapy, even if they achieve a RER.

PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0.

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.

Imaging recommendations in pediatric lymphoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are both malignancies originating in the lymphatic system and both affect children, but many features differ considerably, impacting workup and management. This paper provides consensus-based imaging recommendations for evaluation of patients with HL and NHL at diagnosis and response assessment for both interim and end of therapy (follow-up).

Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma.

PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Patterns of Initial Relapse from a Phase 3 Study of Response-Based Therapy for High-Risk Hodgkin Lymphoma (AHOD0831): A Report from the Children's Oncology Group.

PURPOSE: The Children's Oncology Group protocol AHOD0831, for pediatric patients with high-risk classical Hodgkin lymphoma (cHL), used response-adapted radiation fields, rather than larger involved-field radiation therapy (IFRT) that were historically used. This retrospective analysis of patterns of relapse among patients enrolled in the study was conducted to study the potential effect of a reduction in RT exposure. METHODS AND MATERIALS: From December 2009 to January 2012, 164 eligible patients under 22 years old with stage IIIB (43%) and stage IVB (57%) enrolled on AHOD0831. All patients received 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Those patients with a slow early response (SER) after the first 2 ABVE-PC courses were nonrandomly assigned to 2 intensification cycles with ifosfamide/vinorelbine before the final 2 ABVE-PC cycles. Response-adapted RT (21 Gy) was prescribed to initial areas of bulky disease and SER sites. Rapid early response (RER) sites without bulk were not targeted. Imaging studies at the time of progression or relapse were reviewed centrally for this retrospective analysis. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial nonbulk), initial chemotherapy response, and radiation field (in-field, out-of-field, or both). RESULTS: Of the entire cohort, 140 patients were evaluable for the patterns of failure analyses. To investigate the pattern of failure, this analysis focuses on 23 patients who followed protocol treatment and suffered relapses at a median 1.05 years with 7.97-year median follow-up time. These 23 patients (11 RER and 12 SER) experienced a relapse in 105 total sites (median, 4; range, 1-11). Of the 105 relapsed sites, 67 sites (64%) occurred within an initial site of involvement, with 12 of these 67 sites (18%) at an initial site of bulky disease and 63 of these 67 relapses (94%) occurring in sites that were not fluorodeoxyglucose (FDG)-avid after 2 cycles of ABVE-PC (PET2-negative). Of the 105 relapsed sites, 34 sites (32%) occurred in a new site of disease (that would not have been covered by RT); and, overall, only 4 of 140 patients (2.8%) (occurring in 3 RER and 1 SER) experienced isolated out-of-field relapses that would have been covered by historical IFRT. CONCLUSIONS: For a cohort of high-risk patients with cHL patients, most failures occurred in nonbulky, initially involved sites, largely due to response-based consolidation RT delivered to patients with bulky disease. In this analysis, we discovered low rates of failures outside of these modern risk-adapted radiation treatment volumes. Also, FDG uptake on PET2 did not identify most relapse sites.

PET Imaging for Breast Cancer.

Imaging plays an integral role in the clinical care of patients with breast cancer. This review article focuses on the use of PET imaging for breast cancer, highlighting the clinical indications and limitations of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) PET/CT, the potential use of PET/MRI, and 16α-[18F]fluoroestradiol (FES), a newly approved radiopharmaceutical for estrogen receptor imaging.

Prognostic value of baseline metabolic tumor volume in children and adolescents with intermediate-risk Hodgkin lymphoma treated with chemo-radiation therapy: FDG-PET parameter analysis in a subgroup from COG AHOD0031.

BACKGROUND: Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL). MATERIALS AND METHODS: Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS). RESULTS: From the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012). CONCLUSION: Multiple baseline PET-derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk-based treatment algorithms may improve outcomes in intermediate-risk HL.