Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

BACKGROUND OBJECTIVES: The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. METHODS: A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. RESULTS: Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. INTERPRETATION CONCLUSIONS: Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

Texture analysis of 18F-FDG PET/CT and CECT: Prediction of refractoriness of Hodgkin lymphoma with mediastinal bulk involvement.

To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_EntropyPET ) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_EntropyPET values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_EntropyPET with GHSG stage.

How Early Can Checkpoint Inhibitors Induce a Complete Metabolic Response in Chemorefractory Hodgkin Lymphoma?

ABSTRACT: A 24-year-old man with classical Hodgkin lymphoma was lost to follow-up after metabolic complete remission (mCR). He presented 4 years later with B-symptoms and impaired clinical condition. Relapsed classical Hodgkin lymphoma was diagnosed. PET/CT revealed stage IVB with liver and spleen involvement. Two liver function-adjusted salvage attempts were ineffective. Pembrolizumab was instituted with gradual clinical improvement. PET was missed before treatment for a life-threatening condition and was performed on day +10 showing a near mCR. A mCR was confirmed before cycle 2, on day +21, underlining-for the first time in the literature-the possibility to achieve very early mCR with pembrolizumab.

Adipose tissue indices predict prognosis in hodgkin lymphoma.

INTRODUCTION BACKGROUND: This study evaluated the impact of adipose tissue indices on prognosis of HL. METHODS: Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival. RESULTS: For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant. CONCLUSION: SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.

Left main and three vessels spontaneous coronary artery dissection as an incidental finding in young man with history of Hodgkin's lymphoma-a case report.

BACKGROUND: Spontaneous coronary artery dissection is a rare and important cause of myocardial infarction, especially in young women without other coronary artery disease. This arterial dissection can occur within or between any of the 3 layers. Its predisposing factors include connective tissue diseases (Marfone syndrome, Ehlers-Danlos syndrome), vasculitis (polyarteritis nodosa, systemic lupus erythematosus, and Kawasaki disease), atherosclerosis and fibromuscular dysplasia. Clinical presentations of spontaneous coronary artery dissection are wide spectrum from asymptomatic to acute coronary disease, sustained ventricular arrhythmia and sudden cardiac death. CASE PRESENTATION: We describe A 33-year-old man with history of Hodgkin's lymphoma five years earlier that became a candidate for Patent foramen ovale closure due to recurrent embolic cerebrovascular accident. Before the intervention, coronary angiography incidentally showed dissection in the left main and all major coronary arteries. CONCLUSIONS: Based on our hypothesis, chemoradiotherapy-induced arteriopathies could be consider as a predisposing factor for spontaneous coronary artery dissection.

Comparison of diffusion-weighted MRI and [18F]FDG PET/MRI for treatment monitoring in pediatric Hodgkin and non-Hodgkin lymphoma.

OBJECTIVE: To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([18F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma. MATERIALS AND METHODS: In a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [18F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1-21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [18F]FDG PET/MRI-based response classifications with Gwet's agreement coefficient (AC). RESULTS: After induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [18F]FDG PET/MRI (Gwet's AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet's AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [18F]FDG PET/MRI response assessments (Gwet's AC = 0.97; 95% CI: 0.91, 1). CONCLUSION: Therapy response of Hodgkin lymphoma can be evaluated with either [18F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach. CLINICAL RELEVANCE STATEMENT: Hodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI. KEY POINTS: • Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation. • After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma. • At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types.

A different perspective on PET/CT before treatment in patients with Hodgkin lymphoma: importance of volumetric and dissemination parameters.

The aim of this study is to investigate the role of the combination of volumetric and dissemination parameters obtained from pretreatment 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the interim response and progression status in patients with Hodgkin lymphoma (HL). Pretreatment PET/CT images of HL patients were analyzed with LIFEx software, and volumes of interest (VOIs) were drawn with a fixed SUV 4.0 threshold. MTV, SUVmax, and TLG values were obtained from each VOI. Total MTV (tMTV) was calculated by summing the MTV values in all VOIs, and similarly, total TLG (tTLG) was obtained by summing the TLG values. The distance between the centers of the lesions was noted as Dmax, and the distance between the outermost voxels of the lesions as DmaxVox. tMTV/DmaxVox was calculated by dividing the tMTV value by the DmaxVox value, and tTLG/DmaxVox was calculated by dividing the tTLG value by the DmaxVox value. The correlation of pretreatment PET parameters with response groups (complete/poor) and relapse/progression status (stable/progressive) was statistically evaluated. A total of 52 patients were included in the study. Bulky disease, tMTV, tTLG, and tMTV/DmaxVox values were found to be significantly higher in the poor response group. tMTV > 190.60 ml was found to be the only prognostic factor predicting interim PET response. The tMTV/DmaxVox and tTLG/DmaxVox showed statistically significant differences between the groups with and without progression. tMTV/DmaxVox > 7.70 was found to be the only prognostic factor in predicting relapse/progression. The evaluation of tumor burden and dissemination together in 18F-FDG PET/CT before treatment in patients with HL can help us to predict the results of the patients.

Long-Term Follow-Up of the Response-Adapted Intergroup EORTC/LYSA/FIL H10 Trial for Localized Hodgkin Lymphoma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in ePET-negative patients, the risk of relapse increased when involved-node radiotherapy (INRT) was omitted and that in ePET-positive patients, switching from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) significantly improved 5-year progression-free survival (PFS). Here, we report the final results of a preplanned analysis at a 10-year follow-up. In the favorable (F) ePET-negative group, the 10-year PFS rates were 98.8% versus 85.4% (hazard ratio [HR], 13.2; 95% CI, 3.1 to 55.8; P value for noninferiority = .9735; difference test P < .0001) in favor of ABVD + INRT; in the unfavorable (U) ePET-negative group, the 10-year PFS rates were 91.4% and 86.5% (HR, 1.52; 95% CI, 0.84 to 2.75; P value for noninferiority = .8577; difference test P = .1628). In ePET-positive patients, the difference in terms of PFS between standard ABVD and intensified BEACOPPesc was no longer statistically significant (HR, 0.67; 95% CI, 0.37 to 1.20; P = .1777). In conclusion, the present long-term analysis confirms that in ePET-negative patients, the omission of INRT is associated with lower 10-year PFS. Instead, in ePET-positive patients, no significant difference between standard and experimental arms emerged although intensification with BEACOPPesc was safe, with no increase in late adverse events, namely, second malignancies.

Fluorodeoxyglucose-Positron Emission Tomography in Relapsed/Refractory Hodgkin Lymphoma: A Practical Approach.

BACKGROUND: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low-dosage computer tomography, is to be considered as the most important evolution of imaging in the management and assessment of classical Hodgkin lymphoma patients. SUMMARY: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of nonresponders or refractory disease patients. Refractory disease is reported in about 15% of patients, with some variations based on the choice of first-line chemotherapy, and particularly in advanced stages, up to 40% eventually relapse within 3 years. KEY MESSAGES: The aim of this review was to highlight a practical way to use FDG-PET in the subset of HL, with some notes of its use in first-line patients, and particularly centered on relapsed or refractory setting with a final focus of the evaluation of response by FDG-PET in the new treatment era of immunocheckpoint inhibitors.

Patterns of PET-positive residual tissue at interim restaging and risk of treatment failure in advanced-stage Hodgkin's lymphoma: an analysis of the randomized phase III HD18 trial by the German Hodgkin Study Group.

PURPOSE: Response-adapted treatment using early interim functional imaging with PET after two cycles of chemotherapy (PET-2) for advanced-stage Hodgkin's lymphoma (AS-HL) is the standard of care in several countries. However, the distribution of residual metabolic disease in PET-2 and the prognostic relevance of multiple involved regions have not been reported to date. METHODS: We retrospectively analyzed data from all PET-2-positive patients included in HD18. Residual tissue was visually compared with reference regions according to the Deauville score (DS). PET-2 positivity was defined as residual tissue with uptake above the liver (DS4). PFS was defined as the time from staging until progression, relapse, or death from any cause, or to the day when information was last received on the patient's disease status and analyzed using Kaplan-Meier and Cox regressions. Comparisons were made between patients with 1-2 and >2 positive regions in PET-2 as well as patients without PET-2-positive regions randomized into comparator arms of HD18. RESULTS: Between 2008 and 2014, 1964 patients with newly diagnosed AS-HL were recruited in HD18 and randomized following their PET-2 scan. Of these, 480 patients had a positive PET-2 and were eligible for this analysis. Upper and lower mediastinum in almost half of all patients: 230 (47.9%) and 195 (40.6%), respectively. 372 (77.5%) of patients have 1-2 positive regions in PET-2. 5y-PFS for patients with 1-2 regions was 91.7% (CI95: 88.7-94.6) vs. 81.8% (CI95: 74.2-90.1) for those with >2 regions with a corresponding hazard ratio (HR) of 2.2 (CI95: 1.2-4.0). Compared with patients without PET-2-positive disease receiving 6-8 cycles of chemotherapy, patients with 1-2 had a higher risk for a PFS event (HR 1.35; CI95 0.81-2.28), but it was not statistically significant (p=0.25). Patients with >2 PET-2-positive lesions had a significantly higher risk (HR 2.95; CI95: 1.62-5.37; p<0.001). CONCLUSION: PET-2-positive residuals of AS-HL are mostly located in the mediastinum, and a majority of patients have few affected regions. The risk of progression was twofold higher in patients with more than two positive regions in PET-2.

Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Prognostic Value of Baseline Tumor Burden and Tumor Dissemination Extracted From 18 F-FDG PET/CT in a Cohort of Adult Patients With Early or Advanced Hodgkin Lymphoma.

PURPOSE: We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). PATIENTS AND METHODS: Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%). CONCLUSIONS: Combining baseline TLG with IPS could improve PFS prediction.

Management of limited-stage Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a rare type of B-cell malignancy with bimodal age distribution targeting young adults and elderly. Prognostic models are available to identify risk of recurrence and response to treatment. Currently, positron emission tomography scanning is most useful in optimizing therapy. Outcomes are generally excellent with standard chemotherapy or combined modality therapy. Balancing efficacy and the risk of late effects in Hodgkin lymphoma is essential, including early detection of potential complications. Incorporation of novel therapies such as brentuximab vedotin and checkpoint inhibitors are being explored in the frontline setting, having already demonstrated improved survival and tolerable toxicity in advanced HL. Furthermore, the addition of these agents have the potential to transform treatment paradigms for early-stage HL and may result in improved outcomes with decreased risks of late toxicities that continue to afflict long-term survivors. However, the patient population, sequencing, and combinations with cytotoxic chemotherapy all remain still standing questions as results of current and upcoming randomized trials are awaited. In this article, we discuss the current data on the approach to initial treatment of early-stage classical HL, review toxicity profiles, and examine upcoming novel therapy trials.

Dual adversarial deconfounding autoencoder for joint batch-effects removal from multi-center and multi-scanner radiomics data.

Medical imaging represents the primary tool for investigating and monitoring several diseases, including cancer. The advances in quantitative image analysis have developed towards the extraction of biomarkers able to support clinical decisions. To produce robust results, multi-center studies are often set up. However, the imaging information must be denoised from confounding factors-known as batch-effect-like scanner-specific and center-specific influences. Moreover, in non-solid cancers, like lymphomas, effective biomarkers require an imaging-based representation of the disease that accounts for its multi-site spreading over the patient's body. In this work, we address the dual-factor deconfusion problem and we propose a deconfusion algorithm to harmonize the imaging information of patients affected by Hodgkin Lymphoma in a multi-center setting. We show that the proposed model successfully denoises data from domain-specific variability (p-value < 0.001) while it coherently preserves the spatial relationship between imaging descriptions of peer lesions (p-value = 0), which is a strong prognostic biomarker for tumor heterogeneity assessment. This harmonization step allows to significantly improve the performance in prognostic models with respect to state-of-the-art methods, enabling building exhaustive patient representations and delivering more accurate analyses (p-values < 0.001 in training, p-values < 0.05 in testing). This work lays the groundwork for performing large-scale and reproducible analyses on multi-center data that are urgently needed to convey the translation of imaging-based biomarkers into the clinical practice as effective prognostic tools. The code is available on GitHub at this https://github.com/LaraCavinato/Dual-ADAE .

The clinical utility of PET/CT scan and tissue biopsy in the management and follow-up of paediatric Hodgkin lymphoma in South Africa.

BACKGROUND: In low- to middle-income countries (LMICs) like South Africa, there is a need to understand the clinical practices surrounding diagnosis and surveillance of paediatric Hodgkin lymphoma (HL) to reduce the burden on health systems. Understanding the clinical utility of PET/CT scans may decrease repeated tissue biopsies during disease surveillance. METHODS: This is a retrospective cohort study of patients aged less than 18 years treated for HL at Chris Hani Baragwanath Academic Hospital from 1 January 2009 to 31 December 2018. RESULTS: Fifty-four patients were included in the study; male-to-female ratio was 5:1 with a mean age of 9 years. Seventy per cent of patients (n = 38) received a PET/CT and tissue biopsy during their initial diagnostic workup, whereas 20.4% (n = 11) of patients received a PET/CT and tissue biopsy during surveillance. Tissue biopsy and PET/CT showed slight agreement (κ = 0.14) in diagnosing relapsed disease during surveillance. The false negative rate for tissue biopsy during surveillance was 42.9%. Surveillance PET/CT showed a positive predictive value (PPV) of 66.7% and negative predictive value (NPV) of 100% when compared to tissue biopsy. CONCLUSION: This study is the first cohort to explore the clinical utility of PET/CT scans and tissue biopsies in a lowresourced setting. Our findings showed slight agreement between the modalities in diagnosing relapsed disease during surveillance. A portion of this discordance can be attributed to false negative tissue biopsy results. While the sample is limited, our findings are consistent with the high NPV of PET/CT scans of > 95% as is reported in the literature.

Revisiting the predictive role of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography on treatment outcome in early-stage favorable Hodgkin lymphoma.

In the present manuscript Gallamini et al. comment the results of three large, phase III, randomized clinical trials in early-stage favorable Hodgkin Lymphoma (HL), aimed at exploring the non-inferiority of ABVD chemotherapy alone compared to combined-modality treatment with ABVD and Involved Field/Node Radiotherapy (INRT). The authors also report the preliminary results of risk-stratification in the first 60 enrolled patients in the phase 2, prospective, international study RAFTING: RAdiotherapy Free Treatment IN Good-prognosis early-stage HL (National Trial Identifier 04866654). In this trial patients are stratified, before treatment onset, according to the risk of therapy failure in a single patient basis, taking into account non only the results of interim and End-of-Therapy PET, but also the value of new metrics extracted from the baseline PET/CT such as the Large Nodal Mass (LNM) and Total Metabolic Tumor Volume (TMTV). Treatment intensity, consisting in ABVD chemotherapy, INRT and Nivolumab maintenance, is modulated on the presence/absence of the above factors, in a personalized-medicine approach. The most frequently detected factors driving treatment intensity were LNM and TMTV, while the results of interim and end-of-treatment PET were also determinant, albeit in a lower percentage of cases.

Exoftalmos y dolor ocular como presentación clínica de linfoma de Hodgkin con afectación intracraneal al diagnóstico / Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis

La afectación intracraneal del linfoma de Hodgkin (LH) es extremadamente rara, especialmente como forma de presentación de la enfermedad. Muestra un patrón radiológico inespecífico, pudiendo ser confundido con otras entidades de mayor frecuencia y pronóstico radicalmente distinto. Anatomopatológicamente se caracteriza por la presencia de células grandes binucleadas (células de Reed-Sternberg) eIntracranial involvement in Hodgkin's lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network.

In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presentation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis (AU)mbebidas en un entramado inflamatorio. Presentamos el caso de una paciente con dolor ocular y exoftalmos izquierdo como presentación clínica de afectación intracraneal por LH al diagnóstico de su enfermedad y revisamos la literatura más reciente al respecto. En pacientes con LH intracraneal es necesario realizar un estudio de extensión con tomografía computarizada corporal, biopsia de médula ósea y examen oftalmológico. Se asocia con gran frecuencia a enfermedad extracraneal, que marca el pronóstico. La lesión intracraneal presenta buena respuesta al tratamiento, que no sigue un esquema estandarizado. El papel de la cirugía es la realización de una biopsia para confirmar el diagnóstico (AU)

Real-World Use of Positron Emission Tomography-Computed Tomography and Reported Deauville Scores in Advanced-Stage Classic Hodgkin Lymphoma: A Community Oncology Practice Perspective.

PURPOSE: To evaluate the use of interim positron emission tomography-computed tomography (PET-CT) scans and Deauville 5-point scale (5PS) score reporting for stage III/IV classic Hodgkin lymphoma (cHL) treated frontline (1L) in community oncology settings. METHODS: This retrospective, observational study included adults with stage III/IV cHL initiating 1L doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, or an escalated dosing regimen of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone within the US Oncology Network between January 2017 and October 2019. Data were collected from electronic health records and chart reviews and summarized descriptively. RESULTS: A total of 262 patients were included; 48.9% were age 39 years or younger. Most were male (57%), White (59%), had an International Prognostic Score <4 (76%), and received 1L ABVD (74%). Forty-nine percent of patients had stage III and 51% had stage IV cHL. Of 258 patients with ≥1 PET-CT scan, 71% (n = 184) had an interim scan and 64% received ≥1 scan at an off-site location. Of patients treated 1L with ABVD who received a baseline and interim scan, Deauville 5PS scores were not documented for 45% of patients; in 90% of these cases, a standardized uptake value (SUV) was reported. CONCLUSION: In community oncology settings, under-reporting of Deauville 5PS scores for interim PET-CT scans was observed. In the absence of Deauville 5PS scores, SUV results were generally provided. These results highlight educational opportunities that exist for PET-adapted ABVD, including consistency in reporting/utilization of Deauville 5PS scores to de-escalate or escalate treatment.

[Diagnosis and staging of Hodgkin lymphoma]. / Diagnostic et bilan préthérapeutique du lymphome de Hodgkin.

DIAGNOSIS AND STAGING OF HODGKIN LYMPHOMA. Hodgkin lymphoma (HL) is composed of two distinct disease entities: classical HL (cHL) and nodular lymphocyte predominant HL (NLPHL). NLPHL is a rare entity with a specific therapeutic management. The subgroups of cHL are nodular sclerosis, mixed cellularity, lymphocyte depletion and lymphocyte-rich HL. The initial diagnosis of HL is made by a biopsy to analyze with accuracy the architecture of the lymph node. Most HL patients present with supradiaphragmatic lymphadenopathy. Initial staging is determined by positron emission tomography (PET) scan and bone marrow biopsy is now avoided of initial staging. This staging allows the definition of prognostic groups to determine a risk-adapted initial therapy to maintain a high level of curability and reduce long-term therapeutic side effects. Before initial treatment, cardiac ultrasound and pulmonary function tests are needed. The question of fertility preservation is important to address before treatment and for older patients the requirement of geriatric assessment.

DIAGNOSTIC ET BILAN PRÉTHÉRAPEUTIQUE DU LYMPHOME DE HODGKIN. Les lymphomes de Hodgkin se composent de deux entités distinctes : les lymphomes de Hodgkin classiques, qui représentent les formes les plus fréquentes, et les lymphomes de Hodgkin nodulaires à prédominance lymphocytaire, plus rares et dont la prise en charge est très spécifique. Parmi les lymphomes de Hodgkin classiques, on distingue les sous-types histologiques scléronodulaire, à cellularité mixte, riche en lymphocytes et à déplétion lymphocytaire. Le diagnostic exige une biopsie de bonne qualité, le plus souvent obtenue à la suite d'une exérèse chirurgicale. La présentation clinique est, dans la grande majorité des cas, très stéréotypée, notamment chez les patients les plus jeunes avec la présence d'adénopathies sus-diaphragmatiques. Le bilan d'extension utilise majoritairement la tomographie par émission de positons (TEP) ; une biopsie de moelle n'est actuellement plus nécessaire. Il permet la définition de groupes pronostiques, permettant un traitement au plus juste pour maintenir un taux de guérison élevé et éviter les séquelles tardives. Outre les examens cardiaques et pulmonaires, le bilan préthérapeutique aborde la question de la préservation de la fertilité et de l'évaluation gériatrique chez les patients les plus âgés.

Ultrasonography-guided core-needle biopsy of lymphadenopathies suspected of lymphoma: Analysis on diagnostic efficacy and safety of 1000 front-line biopsies in a multicenter Italian study.

The reliability and safety of front-line ultrasonography guided core needle biopsy (UG-CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG-CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG-CNB from four Italian clinical units that routinely utilized 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG-CNB in untreated patients over a 12-year period. Overall, 1000 (superficial target, n = 750; deep-seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B-cell non-Hodgkin lymphoma [aBc-NHL], 309 cases; indolent B-cell [iBc]-NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T-cell [NPTC]-NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non-malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro-histological sampling was 97% (95% confidence interval: 95%-98%) for the series. The sensitivity of UG-CNB for the detection of aBc-NHL was 100%, for iBc-NHL 95%, for HL 93%, and for NPTC-NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy-related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG-CNB as mini-invasive diagnostic procedure is effective with minimal risk for the patient.