Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis.

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P<0.0001). Five-year PFS/OS rates were 72%/87% after vorinostat/ GemBuMel, 55%/75% after GemBuMel, 45%/61% after BEAM, and 39%/57% after BuMel (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET-negative and PET-positive subgroups. Prior BV and vorinostat/GemBuMel were independent predictors of more favorable outcome, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET-positivity at ASCT correlated independently with unfavorable outcomes. In conclusion, post-HDC/ASCT outcomes of patients with HRR classic Hodgkin lymphoma have improved over the last 15 years. Pre-ASCT BV treatment and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.

Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation.

The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVt and TLGt were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours.

OBJECTIVES: Localization of ectopic ACTH-secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68 Ga]-DOTATATE PET/CT ([68 Ga]-DOTA-(Tyr3 )-octreotate)] is an FDA-approved high-resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utility of [68 Ga]-DOTATATE in patients with ECS, however, are scarce. The objectives of this study were to determine the efficacy for ECS localization and the clinical benefit of [68 Ga]-DOTATATE imaging. METHOD: We conducted a retrospective review of all cases with ECS evaluated with [68 Ga]-DOTATATE from November 2016 through October 2018 at three referral centres. The clinical benefit of [68 Ga]-DOTATATE was based on detection of new tumours and resultant changes in management. RESULTS: Over the study period, 28 patients with ECS underwent [68 Ga]-DOTATATE: 17 for identification of the primary tumour and 11 during follow-up. [68 Ga]-DOTATATE identified the suspected primary ECS in 11/17 patients (65%). Of these, nine patients underwent surgery: eight with confirmed ECS (5 bronchial, 1 thymic, 1 pancreatic and 1 metastatic neuroendocrine tumour of unknown primary origin) and one patient with a false-positive scan (adrenal gland). Of the 11 patients with ECS who underwent [68 Ga]-DOTATATE evaluation during follow-up, the study led to changes in clinical management in 7/11 (64%) patients. CONCLUSIONS: [68 Ga]-DOTATATE is sensitive in detecting primary and metastatic ECS, often identifies occult tumours after conventional imaging, and impacts clinical care in the majority of patients.

Early-stage Hodgkin lymphoma outcomes after combined modality therapy according to the post-chemotherapy 5-point score: can residual pet-positive disease be cured with radiotherapy alone?

Early-stage classical Hodgkin lymphoma (HL) patients are evaluated by an end-of-chemotherapy positron emission tomography-computed tomography (eoc-PET-CT) after doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and before radiation therapy (RT). We determined freedom from progression (FFP) in patients treated with ABVD and RT according to the eoc-PET-CT 5-point score (5PS). Secondarily, we assessed whether patients with a positive eoc-PET-CT (5PS of 4-5) can be cured with RT alone. The cohort comprised 174 patients treated for stage I-II HL with ABVD and RT alone. ABVD was given with a median of four cycles and RT with a median dose of 30·6 Gy. Five-year FFP was 97%. Five-year FFP was 100% (0 relapses/98 patients) for patients with a 5PS of 1-2, 97% (2/65) for a 5PS of 3, 83% (1/8) for a 5PS of 4, and 67% (1/3) for a 5PS of 5 (P < 0·001). Patients with positive eoc-PET-CT scans who were selected for salvage RT alone had experienced a very good partial response to ABVD. Risk factors for recurrence in this subgroup included a small reduction in tumour size and a 'bounce' in ≥1 PET-CT parameter (reduction then rise from interim to final scan). Thus, a positive eoc-PET-CT is associated with inferior FFP; however, appropriately selected patients can be cured with RT alone.

Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with a high proliferation rate. However, the molecular and genetic features that drive the aggressive clinical behavior of DLBCL are not fully defined. Here, we have demonstrated that activated Jun signaling is a frequent event in DLBCL that promotes dissemination of malignant cells. Downregulation of Jun dramatically reduces lymphoma cell adhesion to extracellular matrix proteins, subcutaneous tumor size in nude mice, and invasive behavior, including bone marrow infiltration and interaction with bone marrow stromal cells. Furthermore, using a combination of RNA interference and gene expression profiling, we identified Jun target genes that are associated with disseminated lymphoma. Among them, ITGAV, FoxC1, and CX3CR1 are significantly enriched in patients with 2 or more extranodal sites. Our results point to activated Jun signaling as a major driver of the aggressive phenotype of DLBCL.

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

BACKGROUND: Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. METHODS: Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. FINDINGS: Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. INTERPRETATION: Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. FUNDING: Pharmacyclics LLC, an AbbVie Company.

Fat-Containing Hypermetabolic Masses on FDG PET/CT: A Spectrum of Benign and Malignant Conditions.

OBJECTIVE: This article focuses on identifying the imaging appearances of hypermetabolic fatty masses and masslike lesions on PET/CT and understanding the diagnostic challenges radiologists may face while interpreting findings of these lesions on PET/CT. This article provides an approach to aid in the diagnosis of these lesions and the appropriate management of patients. CONCLUSION: Both malignant and benign fat-containing masses and masslike lesions can show hypermetabolic activity on PET/CT. Although the differential diagnosis is broad, clinical history, anatomic location, and knowledge of anatomic variants and imaging features can help radiologists avoid misinterpretation of benign fatty lesions as malignancy.

The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma.

The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n = 229), based on Deauville criteria. In early stage non-bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3-year progression-free survival rates in PET2-negative vs. PET2-positive groups were 95·9% vs. 76·9% (P < 0·0018), 83·3% vs. 20·0% (P = 0·017), 77·0% vs. 30·0% (P < 0·001) and 71·0% vs. 44·4%(P = 0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non-randomized studies of PET2-guided therapy would be valuable with careful interpretation.

Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma.

In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m(2) weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHL was 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial.

Impact of ¹8F-FDG PET/CT on the management of adrenocortical carcinoma: analysis of 106 patients.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available about on value of (18)F-FDG PET/CT in ACC. We evaluated the impact of PET/CT on the management of ACC. METHODS: We performed a retrospective review in patients with ACC who had undergone PET/CT. The impact of PET/CT on the management plan was evaluated by comparing the findings on PET/CT to the findings on contrast-enhanced CT. The sensitivity, specificity, and accuracy of each form of imaging were calculated. The correlations between PET/CT parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis, and decline in SUVmax after chemotherapy, and clinical outcome were evaluated. RESULTS: Included in the analysis were 106 patients with 180 PET/CT scans. Of the 106 patients, 7 underwent PET/CT only for initial staging, 84 underwent PET/CT only for restaging, and 15 underwent PET/CT for both initial staging and restaging. PET/CT changed the management plan in 1 of 22 patients (5%) at initial staging and 9 of 99 patients (9%) at restaging. In 5 of the patients in whom PET/CT changed the management plan, PET/CT showed response to chemotherapy but contrast-enhanced CT showed stable disease. Sensitivity, specificity, and accuracy were 100%, 100%, and 100% for PET/CT at initial staging; 92.6%, 100%, and 96.4% for CT at initial staging; 98.4%, 100%, and 99.5% for PET/CT at restaging; and 96.8%, 98.6%, and 98.0% for CT at restaging, respectively. No PET/CT parameters were associated with survival at either initial diagnosis or recurrence. CONCLUSION: PET/CT findings could substantially change the management plan in a small proportion of patients with ACC. Although lesion detection was similar between PET/CT and CT, PET/CT may be preferred for chemotherapeutic response assessment because it may predict response before anatomic changes are detected on CT.

The value of ¹8F-FDG PET/CT in the management of malignant peripheral nerve sheath tumors.

PURPOSE: Our objective was to determine how positron emission tomography (PET)/CT had been used in the clinical treatment of malignant peripheral nerve sheath tumor (MPNST) patients at The University of Texas MD Anderson Cancer Center. METHODS: We reviewed a database of MPNST patients referred to MD Anderson Cancer Center during 1995-2011. We enrolled 47 patients who underwent PET/CT imaging. Disease stage was based on conventional imaging and PET/CT findings using National Comprehensive Cancer Network (NCCN) guidelines. Treatment strategies based on PET/CT and conventional imaging were determined by chart review. The maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), change in SUVmax, change in MTV, and change in TLG were calculated from the PET/CT studies before and after treatment. Response prediction was based on imaging studies performed before and after therapy and categorized as positive or negative for residual tumor. Clinical outcome was determined from chart review. RESULTS: PET/CT was performed for staging in 16 patients, for restaging in 29 patients, and for surveillance in 2 patients. Of the patients, 88 % were correctly staged with PET/CT, whereas 75 % were correctly staged with conventional imaging. The sensitivity to detect local recurrence and distant metastasis at restaging was 100 and 100 % for PET/CT compared to 86 and 83 % for conventional imaging, respectively. PET/CT findings resulted in treatment changes in 31 % (5/16) and 14 % (4/29) of patients at staging and restaging, respectively. Recurrence, MTV, and TLG were prognostic factors for survival, whereas SUVmax and SUVmean were not predictive. For 21 patients who had imaging studies performed both before and after treatment, PET/CT was better at predicting outcome (overall survival, progression-free survival) than conventional imaging. A decreasing SUVmax ≥ 30 % and decrease in TLG and MTV were significant predictors for overall and progression-free survival. CONCLUSION: PET/CT is valuable in MPNST management because of its high accuracy in staging and high sensitivity and accuracy in restaging as well as improvements in treatment planning. MTV from baseline staging studies is predictive of survival. Additionally, change in SUVmax, TLG, and MTV accurately predicted outcomes after treatment.

FDG PET/CT of primary bone tumors.

OBJECTIVE: Numerous primary bone tumors are encountered on (18)F-FDG PET/CT, and many are FDG avid. The degree of FDG uptake in bone tumors does not necessarily reflect malignant potential. In conjunction with radiographs, evaluation of morphologic characteristics on the CT portion of PET/CT scans is important for characterization of the lesions. FDG PET/CT has been found to be useful for staging and has also been found to reflect prognosis in some primary bone malignancies. The purpose of this article is to familiarize the reader with topics regarding FDG PET/CT and both malignant and benign primary bone tumors. CONCLUSION: FDG uptake alone is not adequate for characterizing primary bone tumors, and morphologic evaluation is an important factor in the interpretation of PET/CT scans. After diagnosis, FDG avidity and morphologic features can play an important role in staging and determining response to therapy. On completion of this article, readers should have an improved ability to evaluate the FDG uptake and CT morphologic features of malignant and benign primary bone tumors. Readers should also have a better understanding of the potential role of FDG PET/CT in the management of patients with osteosarcoma and Ewing sarcoma.

Deciphering Tumor Response: The Role of Fluoro-18-d-Glucose Uptake in Evaluating Targeted Therapies with Tyrosine Kinase Inhibitors.

Background/Objectives: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [18F]FDG-PET monitoring of tumor response in patients. Methods: To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [18F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. Results: Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. Conclusions: These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [18F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.

Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma.

We conducted a prospective randomized phase II study to evaluate two chemotherapy regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-HCVAD) alternating with rituximab, high-dose methotrexate, and cytarabine (R-MA) and (ii) rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in diffuse large B-cell lymphoma (DLBCL). This study randomized patients aged ≤60 years with DLBCL and an age-adjusted international prognostic index ≥2 to R-HCVAD/R-MA or R-CHOP based on a Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients showed that the complete response rate (CRR) was higher with R-HCVAD/R-MA than R-CHOP (P = 0·03); thus, R-CHOP arm was closed. In the final analysis, 49 and 10 eligible patients were treated in R-HCVAD/R-MA and R-CHOP arms respectively; CRR were 82% and 60% respectively (P = 0·13); 3-year progression-free survival (PFS) rates were 75·7% and 77·8% respectively (P = 0·53). In the R-HCVAD/R-MA arm, 3-year PFS rates in patients aged 46-60 years and ≤45 years were 70·3% and 87·1% respectively (P = 0·13), and the treatment-associated early mortality rate in patients >45 years was 12%. In conclusion, R-HCVAD/R-MA is associated with excellent outcome in patients ≤45 years old. However, in patients >45 years old, R-HCVAD/R-MA is associated with unacceptable mortality rates.

Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma.

Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma. In this case report, we discuss the case of a patient with a EWSR1-NFATC2 fusion positive bone sarcoma who had exceptional tumor control through using pazopanib and surgery for an overall duration exceeding 5 years. We also review the literature on EWSR1-NFATC2 translocation-associated sarcomas and use of pazopanib in bone sarcomas.

A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

Investigating the limit of detectability of a positron emission mammography device: a phantom study.

PURPOSE: A new positron emission mammography (PEM) device (PEM Flex Solo II, Naviscan Inc., San Diego, CA) has recently been introduced and its performance characteristics have been documented. However, no systematic assessment of its limit of detectability has been evaluated. The aim of this work is to investigate the limit of detectability of this new PEM system using a novel, customized breast phantom. METHODS: Two sets of F-18 infused gelatin breast phantoms of varying thicknesses (2, 4, 6, and 8 cm) were constructed with and without (blank) small, shell-less contrast objects (2 mm thick disks) of varying diameters (3-14.5 mm) [volumes: 0.15-3.3 cc] and activity concentration to background ratio (ACR) (2.7-58). For the phantom set with contrast objects, the disks were placed centrally inside the phantoms and both phantom sets were imaged for a period of 10 min on the PEM device. In addition, scans for the 2 and 6 cm phantoms were repeated at different times (0, 90, and 150 min) post phantom construction to evaluate the impact of total activity concentration (count density) on lesion detectability. Each object from each phantom scan was then segmented and placed randomly in a corresponding blank phantom image. The resulting individual images were presented blindly to seven physician observers (two nuclear medicine and five breast imaging radiologists) and scored in a binary fashion (1-correctly identified object, 0-incorrect). The sensitivity, specificity, and accuracy of lesion detectability were calculated and plots of sensitivity versus ACR and lesion diameters for different phantom thicknesses and count density were generated. RESULTS: The overall (mean) detection sensitivity across all variables was 0.68 (95% CI: [0.64, 0.72]) with a corresponding specificity of 0.93 [0.87, 0.98], and diagnostic accuracy of 0.72 [0.70, 0.75]. The smallest detectable object varied strongly as a function of ACR, as sensitivity ranged from 0.36 [0.29, 0.44] for the smallest lesion size (3 mm) to 0.80 [0.75, 0.84] for the largest (14.5 mm). CONCLUSIONS: The detectability performance of this PEM system demonstrated its ability to resolve small objects with low activity concentration ratios which may assist in the identification of early stage breast cancer. The results of this investigation can be used to correlate lesion detectability with tumor size, ACR, count rate, and breast thickness.

A CT acquisition technique to generate images at various dose levels for prospective dose reduction studies.

OBJECTIVE: The purpose of this article is to determine whether the average of N CT images acquired at a particular dose (D) has image noise equivalent to that of a single image acquired at a dose of N × D. MATERIALS AND METHODS: An electron density phantom, an image quality phantom, and an adult anthropomorphic phantom were scanned multiple times on a 16-MDCT scanner at five effective tube current-rotation time product (mAs) settings (130 kVp; 12, 24, 48, 72, and 144 mAs). Lower-mAs images were averaged to simulate higher-mAs images. Differences in CT number and image noise between simulated and acquired images were quantified using the electron density phantom. Image quality phantom images were scored by three physicists to investigate differences in low- and high-contrast resolution. A forced-choice observer study was performed with three radiologists using anthropomorphic phantom images to evaluate differences in overall image quality. RESULTS: The CT number was, on average, reproduced to within 1 HU, and image noise was reproduced to within 4%, which is below the threshold for visibly perceptible differences in noise. Low- and high-contrast resolution were not degraded, and simulated images were visually indistinguishable from acquired images. CONCLUSION: For the dose range studied, it was concluded that the image quality of a CT image produced by averaging multiple low-mAs CT images is identical to that of a high-mAs image acquired at equivalent effective dose, when all other acquisition and reconstruction parameters are held constant. Prospective CT dose-reduction studies may be feasible by acquiring multiple low-dose scans instead of a single high-dose scan. Simulated high-dose images could be interpreted clinically, whereas lower-dose images would be available for an observer study.

Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma.

The majority of patients with classical Hodgkin lymphoma (cHL) may be cured, but for patients with relapsed or refractory (R/R) cHL, the prognosis is unfavorable. Immune dysfunction is a significant contributor of relapse and a hallmark of cHL; in particular, the immune system is unable to eradicate lymphoma cells that overexpress immune checkpoint proteins. The blocking of this mechanism used by lymphoma cells to evade the immune system has resulted in clinical benefits. Use of checkpoint inhibitors (CPIs) in R/R cHL is associated with high response rates and an acceptable adverse effects profile. There is growing interest in combining chemotherapy with CPIs in frontline therapy of cHL treatment to improve relapse rates without significant additive toxicity. In this review, we discuss the current evidence supporting CPI use in R/R cHL and maintenance therapy. We present emerging CPI data in frontline adult cHL and assess its role in the elderly. In addition, we discuss critical immune-related toxicities and their management, and elaborate on the challenges of monitoring response and minimal residual disease as tools for maximizing efficacy by limiting toxicity.