Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL.

Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p < 0.04) but more somatic variants (p < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 (BCL2) gains and 6q and 9p21.3 (CDKN2A/B) deletions. PIM1, MYD88 L265P , CD79B, TBL1XR1, MEF2B, CIITA, EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.

Integration of big data analytics in the investigation of the relationship between acromegaly and cancer.

OBJECTIVE: To evaluate the association between acromegaly and cancer and different types of cancer by using natural language processing systems and big data analytics. MATERIAL AND METHODS: We conducted an observational, retrospective study utilizing data from the electronic health records (EHRs) of Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. Information from the EHRs was extracted using artificial intelligence techniques and analyzed using Savana Manager 4.0 software. RESULTS: Out of a total of 708,047 registered patients (54.7% females), 544 patients (0.08%; 330 women, 60.7%; mean age at diagnosis 53.0±15.8 yr) were diagnosed with acromegaly. The incidence of cancer was higher in patients with acromegaly vs those without this condition (7.7% vs 3.9%, p<0.001; OR, 2.047, 95%CI, 1.493-2.804). Male acromegalic patients had a higher prevalence of cancer vs females (57.1% vs 42.9%, p=0.012). A significantly higher prevalence of colorectal cancer (2.9% vs 1.4%, p=0.006), bladder cancer (1.1% vs 0.3%, p=0.005), and lymphoma (1.1% vs 0.3%, p=0.009) was observed in patients with acromegaly vs those without the condition. Acromegalic men had significantly higher prevalence rates of colorectal cancer (4.7% vs 1.3%, p=0.001), bladder cancer (2.8% vs 0.4%, p<0.001), breast cancer (0.9% vs 0.2%, p=0.042), gastric cancer (0.9% vs 0.1%, p=0.011), lymphoma (1.4% vs 0.3%, p=0.037), and liver cancer (0.9% vs 0.1%, p=0.012) vs non-acromegalic men. On the other hand, acromegalic women showed a higher prevalence of thyroid cancer (1.2% vs 0.4%, p=0.043) vs non-acromegalic women. CONCLUSION: Our study, based on artificial intelligence techniques and analysis of real-world data and information, revealed a significant association between acromegaly and cancer in our hospital population, mainly acromegalic men, with a higher frequency of colorectal cancer, bladder cancer and lymphoma in particular.

Bluetongue Virus in the Iberian Lynx (Lynx pardinus), 2010-2022.

Clinical infection and death caused by bluetongue virus infection has been reported in the Eurasian lynx. Bluetongue virus surveillance in the Iberian lynx revealed widespread and repeated exposure to serotypes 1 and 4 in wild and captive populations of this species. This exposure is possibly from a spillover event from sympatric ruminants.

A multi-target ligand (JM-20) prevents morphine-induced hyperalgesia in naïve and neuropathic rats.

The present study examines the possible inhibitory effect of JM-20, a multi-target neuroprotective compound, on the development of morphine-induced hyperalgesia in Male Sprague-Dawley naïve rats. Additionally, the impact of JM-20 on chronic constriction injury (CCI) rats under chronic morphine exposure was investigated, and its efficacy in reducing mechanical hypersensitivity and histopathological changes in the sciatic nerve was assessed. JM-20 (20 mg/kg, per os [p.o.]), administered 60 min before morphine (10 mg/kg, s.c. twice daily at 12 h intervals) for ten days, significantly inhibited the development of morphine-induced hyperalgesia assessed using an electronic pressure-meter paw test, hot-plate, and formalin test, as well as the appearance of spontaneous withdrawal somatic symptoms in rats. Furthermore, JM-20 decreases spinal pro-inflammatory interleukin-1ß and restores glutathione to close physiological concentrations, biomarkers directly related to the intensity of mechanical hypernociception. After CCI and sham surgery, co-treatment with JM-20 (10 mg/kg, p.o.) for five days decreased morphine increased-mechanical hypersensitivity, even 12 days after its discontinuation. Continued morphine treatment imposed a neuroinflammatory challenge in CCI animals, further increasing cellularity (>75% immune cell infiltration) with lymphocytes and macrophages. However, JM-20 co-treatment still reduced the presence of cellular infiltrates (51-75%) with a predominance of lymphocytes. Even in the absence of nerve injury, JM-20 attenuated the peripheral neuroinflammatory response observed in morphine-treated sham-operated animals (0% vs. 1-25%). These findings suggest that JM-20 could prevent morphine-induced hyperalgesia by anti-inflammatory and antioxidant mechanisms.

Identification of a multi-modal mechanism for Se(VI) reduction and Se(0) allotropic transition by Stenotrophomonas bentonitica.

Microorganisms can play a key role in selenium (Se) bioremediation and the fabrication of Se-based nanomaterials by reducing toxic forms (Se(VI) and Se(IV)) into Se(0). In recent years, omics have become a useful tool in understanding the metabolic pathways involved in the reduction process. This paper aims to elucidate the specific molecular mechanisms involved in Se(VI) reduction by the bacterium Stenotrophomonas bentonitica. Both cytoplasmic and membrane fractions were able to reduce Se(VI) to Se(0) nanoparticles (NPs) with different morphologies (nanospheres and nanorods) and allotropes (amorphous, monoclinic, and trigonal). Proteomic analyses indicated an adaptive response against Se(VI) through the alteration of several metabolic pathways including those related to energy acquisition, synthesis of proteins and nucleic acids, and transport systems. Whilst the thioredoxin system and the Painter reactions were identified to play a crucial role in Se reduction, flagellin may also be involved in the allotropic transformation of Se. These findings suggest a multi-modal reduction mechanism is involved, providing new insights for developing novel strategies in bioremediation and nanoparticle synthesis for the recovery of critical materials within the concept of circular economy.

Ibrutinib in Combination with R-GemOx in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma of Nongerminal Center B-cell-like Type: Phase II Clinical Trial of the Spanish GELTAMO Group.

PURPOSE: This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histologic diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem-cell transplantation. Patients received an induction treatment consisting of six or eight cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate after four cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The overall response rate and complete remission rate after the fourth cycle were 53% [95% confidence interval (CI), 41-65] and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance, and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year progression-free survival and overall survival were 18% (95% CI, 8-28) and 26% (95% CI, 14-37), respectively. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (44%), neutropenia (30%), and anemia (14%). Grade ≥3 infectious and cardiovascular treatment-related adverse events were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

Metal-Organic Frameworks: Unconventional Nanoweapons against COVID.

The SARS-CoV-2 (COVID-19) pandemic outbreak led to enormous social and economic repercussions worldwide, felt even to this date, making the design of new therapies to combat fast-spreading viruses an imperative task. In the face of this, diverse cutting-edge nanotechnologies have risen as promising tools to treat infectious diseases such as COVID-19, as well as challenging illnesses such as cancer and diabetes. Aside from these applications, nanoscale metal-organic frameworks (nanoMOFs) have attracted much attention as novel efficient drug delivery systems for diverse pathologies. However, their potential as anti-COVID-19 therapeutic agents has not been investigated. Herein, we propose a pioneering anti-COVID MOF approach by studying their potential as safe and intrinsically antiviral agents through screening various nanoMOF. The iron(III)-trimesate MIL-100 showed a noteworthy antiviral effect against SARS-CoV-2 at the micromolar range, ensuring a high biocompatibility profile (90% of viability) in a real infected human cellular scenario. This research effectively paves the way toward novel antiviral therapies based on nanoMOFs, not only against SARS-CoV-2 but also against other challenging infectious and/or pulmonary diseases.

Rice Husk-Based Insulators: Manufacturing Process and Thermal Potential Assessment.

The development of bio-insultation materials has attracted increasing attention in building energy-saving fields. In tropical and hot-humid climates, building envelope insulation is important for an energy efficient and comfortable indoor environment. In this study, several experiments were carried out on a bio-insulation material, which was prepared by using rice husk as a raw material. Square rice husk-based insultation panels were developed, considering the ASTM C-177 dimensions, to perform thermal conductivity coefficient tests. The thermal conductivity coefficient obtained was 0.073 W/(m K), which is in the range of conventional thermal insulators. In a second phase of this study, two experimental enclosures (chambers) were constructed, one with rice husk-based insulation panels and the second one without this insulation. The measures of the temperatures and thermal flows through the chambers were obtained with an electronic module based on the ARDUINO platform. This module consisted of three DS18B20 temperature sensors and four Peltier plates. Daily temperature and heat flux data were collected for the two chambers during the dry season in Panama, specifically between April and May. In the experimental chamber that did not have rice husk panel insulation on the roof, a flow of up to 28.18 W/m2 was observed, while in the chamber that did have rice husk panels, the presence of a flow toward the interior was rarely observed. The rice husk-based insulation panels showed comparable performance with conventional insulators, as a sustainable solution that takes advantage of a local resource to improve thermal comfort and the reduction of the environmental impact.

Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Safety and efficacy of parsaclisib in combination with rituximab, bendamustine + rituximab, or ibrutinib in patients with previously treated B-cell lymphoma: analysis of a phase 1 dose-finding study (CITADEL­112).

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen can be safely diagnosed by a core percutaneous ultrasound-guided biopsy.

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign lesion of the spleen. SANT cannot be distinguished from other benign or malignant splenic tumors based on imaging findings. So, diagnosis relies on histopathologic examination. Although splenectomy is frequently considered as an option, core needle biopsy tissue analysis is safe and accurate to avoid surgery.

Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation.

Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

Long-term surveillance of the feline leukemia virus in the endangered Iberian lynx (Lynx pardinus) in Andalusia, Spain (2008-2021).

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.

Pain as a disease in the new International Classification of Diseases (ICD-11): Latin American expert consensus.

Aims: Pain diagnoses in the 10th version of the International Classification of Diseases (ICD-10) did not adequately support the current management of pain. Therefore, we aimed to review the new 11th revision (ICD-11) in order to analyze its usefulness for the management, coding, research and education of chronic pain from a Latin American perspective. Methods: The Latin American Federation of Associations for the Study of Pain convened a meeting of pain experts in Lima, Peru. Pain specialists from 14 Latin American countries attended the consensus meeting. Results: In ICD-11, chronic pain is defined as pain that persists or recurs longer than 3 months and is subdivided into seven categories: chronic primary pain and six types of chronic secondary pain. Chronic primary pain is now considered a disease in itself, and not a mere symptom of an underlying disease. Conclusion: The novel definition and classification of chronic pain in ICD-11 is helpful for better medical care, research and health statistics. ICD-11 will improve chronic pain management in Latin American countries, for both the pain specialist and the primary care physician.

Chronic pain is one of the most frequent reasons for medical consultation in Latin America. In the tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10), chronic pain was not adequately defined and individual pain diagnoses were poorly defined. For the first time in Latin America, a meeting of pain experts analyzed and reviewed the 11th version of the International Classification of Diseases (ICD-11), when the Latin America Federation of Associations for the Study of Pain organized a meeting of experts from 14 Latin American countries. In ICD-11, chronic pain is recognized as a biopsychosocial phenomenon and defined as pain that continues or returns for more than 3 months. It is split into seven types: chronic primary pain and six types of chronic secondary pain. In ICD-11, chronic primary pain is now considered a disease in itself, not a mere manifestation of other disease. Our article is the first to address the problems, challenges and benefits of using ICD-11 from a Latin American perspective. It will help to facilitate and disseminate the use of this new classification of chronic pain. This will improve chronic pain treatment, statistics, research and development of better health strategies for pain management in Latin America.

An Approach to Establishing Diagnostic Reference Levels in Interventional Pediatric Cardiology from Different Regions of Brazil.

Diagnostic reference levels (DRLs) are a pivotal strategy to be implemented since pediatric interventional cardiology procedures are increasing. This work aimed to propose an initial set of Brazilian DRLs for pediatric interventional diagnostic and therapeutic (D&T) procedures. A retrospective study was carried out in four Brazilian states, distributed across the three regions of the country. Data were collected from pediatric patients undergoing cardiac interventional procedures (CIPs), including their age and anthropometric characteristics, and at least four parameters (number of images, exposure time, air kerma-area product-PKA, and cumulative air kerma). Data from 279 patients undergoing CIPs were gathered (147 diagnostic and 132 therapeutic procedures). There were no significant differences in exposure time and the number of images between the D&T procedures. A wide range of PKA was observed when the therapeutic procedures were compared to diagnostics for all age groups. There were significant differences between the D&T procedures, whether grouping data by patient weight or age. In terms of cumulative air kerma, it was noted that no value exceeded the level to trigger a monitoring process for patients. This study shows that it is possible to adopt them as the first proposal to establish national DRLs considering pediatric patient groups.

A rare case of Salmonella-associated acute pancreatitis in a patient with ulcerative colitis.

Inflammatory bowel disease is a known risk factor for enteric infections such as Salmonella. This infection can affect almost all major organs. Acute Salmonella pancreatitis is a rare complication. This is the case of a 61-year-old man with ulcerative colitis who developed acute pancreatitis complicating Salmonella infection.

Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma.

The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel (P = 0.0002 for B cell GES; P = 0.0165 for CD19 expression) but not SOC (P = 0.9374 for B cell GES; P = 0.5526 for CD19 expression). Axi-cel showed superior event-free survival over SOC irrespective of B cell GES and CD19 expression (P = 8.56 × 10-9 for B cell GES high; P = 0.0019 for B cell GES low; P = 3.85 × 10-9 for CD19 gene high; P = 0.0017 for CD19 gene low). Low CD19 expression in malignant cells correlated with a tumor GES consisting of immune-suppressive stromal and myeloid genes, highlighting the inter-relation between malignant cell features and immune contexture substantially impacting axi-cel outcomes. Tumor burden, lactate dehydrogenase and cell-of-origin impacted SOC more than axi-cel outcomes. T cell activation and B cell GES, which are associated with improved axi-cel outcome, decreased with increasing lines of therapy. These data highlight differences in resistance mechanisms to axi-cel and SOC and support earlier intervention with axi-cel.

Foamy Macrophages in a Case of Mononucleosis With Amoxicillin-Induced Rash, Hyperlipidemia, and Hemophagocytic Lymphohistiocytosis.

ABSTRACT: A 38-year-old man presented with fever, cough, and jaundice. Four days before, he had started taking amoxicillin/clavulanic acid. He subsequently developed a morbilliform rash, and, according to clinical features and blood analyses, a diagnosis of mononucleosis with Epstein-Barr virus-associated antibiotic-induced exanthema and secondary hemophagocytic lymphohistiocytosis was made. A skin biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with interface dermatitis and many foamy macrophages in the papillary dermis and around the vessels of the superficial dermal plexus. A blood lipid test uncovered marked hypercholesterolemia and hypertriglyceridemia. After treatment with dexamethasone and immunoglobulin, the skin rash, liver function, and lipid profile progressively improved. Xanthomatous cells have been observed in skin biopsies of acute graft-versus-host disease with liver involvement, and these cells have been suggested to represent a clue to the presence of hepatic disease. In our case, underlying cholestatic hepatopathy with hyperlipidemia was present. We believe that the incidental finding of foamy cells in graft-versus-host disease cases and in our case are likely related to the presence of severe liver disease with cholestatic hepatopathy and secondary hyperlipidemia in different background conditions.

A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma.

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.