Mind the gap: reconciling tropical forest carbon flux estimates from earth observation and national reporting requires transparency.

BACKGROUND: The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be "managed" by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. RESULTS: Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (- 0.2 GtCO2yr-1), while Brazil's NGHGI reported a net carbon source (+ 0.8 GtCO2yr-1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory's methodology, the EO net flux became a source of + 0.6 GtCO2yr-1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr-1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr-1; Global EO: + 0.2 GtCO2 yr-1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. CONCLUSIONS: By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remaining differences can be explained. Despite limited spatial data available for Indonesia and Malaysia, our comparison indicated specific aspects where differing approaches may explain divergence, including uncertainties and inaccuracies. Our study highlights the importance of enhanced transparency, as set out by the Paris Agreement, to enable alignment between different approaches for independent measuring and verification.

Spatial database of planted forests in East Asia.

Planted forests are critical to climate change mitigation and constitute a major supplier of timber/non-timber products and other ecosystem services. Globally, approximately 36% of planted forest area is located in East Asia. However, reliable records of the geographic distribution and tree species composition of these planted forests remain very limited. Here, based on extensive in situ and remote sensing data, as well as an ensemble modeling approach, we present the first spatial database of planted forests for East Asia, which consists of maps of the geographic distribution of planted forests and associated dominant tree genera. Of the predicted planted forest areas in East Asia (948,863 km2), China contributed 87%, most of which is located in the lowland tropical/subtropical regions, and Sichuan Basin. With 95% accuracy and an F1 score of 0.77, our spatially-continuous maps of planted forests enable accurate quantification of the role of planted forests in climate change mitigation. Our findings inform effective decision-making in forest conservation, management, and global restoration projects.

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Rates and drivers of aboveground carbon accumulation in global monoculture plantation forests.

Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.

A global map of planting years of plantations.

Plantation is an important land use type that differs from natural forests and affects the economy and the environment. Tree age is one of the key factors used to quantify the impact of plantations. However, there is a lack of datasets explicitly documenting the planting years of global plantations. Here we used time-series Landsat archive from 1982 to 2020 and the LandTrendr algorithm to generate global maps of planting years based on the global plantation extent products in Google Earth Engine (GEE) platform. The datasets developed in this study are in a GeoTIFF format with 30-meter spatial resolution by recording gridded specie types and planting years of global plantations. The derived dataset could be used for yield prediction of tree crops and social and ecological cost-benefit analysis of plantations.

Changes in global terrestrial live biomass over the 21st century.

Live woody vegetation is the largest reservoir of biomass carbon, with its restoration considered one of the most effective natural climate solutions. However, terrestrial carbon fluxes remain the largest uncertainty in the global carbon cycle. Here, we develop spatially explicit estimates of carbon stock changes of live woody biomass from 2000 to 2019 using measurements from ground, air, and space. We show that live biomass has removed 4.9 to 5.5 PgC year-1 from the atmosphere, offsetting 4.6 ± 0.1 PgC year-1 of gross emissions from disturbances and adding substantially (0.23 to 0.88 PgC year-1) to the global carbon stocks. Gross emissions and removals in the tropics were four times larger than temperate and boreal ecosystems combined. Although live biomass is responsible for more than 80% of gross terrestrial fluxes, soil, dead organic matter, and lateral transport may play important roles in terrestrial carbon sink.

New forest biomass carbon stock estimates in Northeast Asia based on multisource data.

Forests play an important role in both regional and global C cycles. However, the spatial patterns of biomass C density and underlying factors in Northeast Asia remain unclear. Here, we characterized spatial patterns and important drivers of biomass C density for Northeast Asia, based on multisource data from in situ forest inventories, as well as remote sensing, bioclimatic, topographic, and human footprint data. We derived, for the first time, high-resolution (1 km × 1 km) maps of the current and future forest biomass C density for this region. Based on these maps, we estimated that current biomass C stock in northeastern China, the Democratic People's Republic of Korea, and Republic of Korea to be 2.53, 0.40, and 0.35 Pg C, respectively. Biomass C stock in Northeast Asia has increased by 20%-46% over the past 20 years, of which 40%-76% was contributed by planted forests. We estimated the biomass C stock in 2080 to be 6.13 and 6.50 Pg C under RCP4.5 and RCP8.5 scenarios, respectively, which exceeded the present region-wide C stock value by 2.85-3.22 Pg C, and were 8%-14% higher than the baseline C stock value (5.70 Pg C). The spatial patterns of biomass C densities were found to vary greatly across the Northeast Asia, and largely decided by mean diameter at breast height, dominant height, elevation, and human footprint. Our results suggest that reforestation and forest conservation in Northeast Asia have effectively expanded the size of the carbon sink in the region, and sustainable forest management practices such as precision forestry and close forest monitoring for fire and insect outbreaks would be important to maintain and improve this critical carbon sink for Northeast Asia.

Mapping carbon accumulation potential from global natural forest regrowth.

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy.

Exposure to microcystin among coastal residents during a cyanobacteria bloom in Florida.

Florida has experienced multiple cyanobacteria blooms in recent years the most severe of which occurred in 2016 and 2018. Several toxins are produced by proliferating cyanobacteria, including the hepatotoxin microcystin (MC). Harmful algal blooms (HABs) caused by cyanobacteria have the potential to impact public health. However, to date there have been limited attempts to quantify exposure in human populations. This study investigated potential exposure to the cyanobacterial toxin, MC by measuring concentrations in swabs of the nasal mucosa. In addition, the relationships between nasal concentrations of MC, environmental concentrations and activity patterns were assessed. Participants (n = 125) were recruited in 2018 during a cyanobacterial bloom of Microcystis aeruginosa and completed a questionnaire which included location, type, and duration of recreational or occupational contact with impacted waterways within the last 10 days. Water samples were collected concurrently. A sterile swab was used to collect a sample from the nasal mucosa. Concentrations of MC were measured by ELISA. Of the 121 participants who provided nasal swabs, 115 (95.0 %) had concentrations of MC above the limit of detection with a mean concentration of 0.61 + 0.75 ppb. There were significant differences (p < 0.01) in mean MC concentration between individuals with direct contact with impacted waters (0.77 + 0.88 ppb) compared to those with no recent contact (0.37 + 0.49 ppb). Higher concentrations were observed among occupationally exposed individuals. Nasal concentrations of MC varied significantly over time and location of exposure to the bloom, concordant with concentrations in water samples. The results suggest that inhalation of aerosols may be an important pathway for exposure to MC. Nasal MC concentrations were generally highest during periods when concentrations in the surrounding waters peaked. Further research is needed to characterize the public health implications of exposure to cyanobacterial blooms.

Degradation and forgone removals increase the carbon impact of intact forest loss by 626.

Intact tropical forests, free from substantial anthropogenic influence, store and sequester large amounts of atmospheric carbon but are currently neglected in international climate policy. We show that between 2000 and 2013, direct clearance of intact tropical forest areas accounted for 3.2% of gross carbon emissions from all deforestation across the pantropics. However, full carbon accounting requires the consideration of forgone carbon sequestration, selective logging, edge effects, and defaunation. When these factors were considered, the net carbon impact resulting from intact tropical forest loss between 2000 and 2013 increased by a factor of 6 (626%), from 0.34 (0.37 to 0.21) to 2.12 (2.85 to 1.00) petagrams of carbon (equivalent to approximately 2 years of global land use change emissions). The climate mitigation value of conserving the 549 million ha of tropical forest that remains intact is therefore significant but will soon dwindle if their rate of loss continues to accelerate.

Estimating aboveground net biomass change for tropical and subtropical forests: Refinement of IPCC default rates using forest plot data.

As countries advance in greenhouse gas (GHG) accounting for climate change mitigation, consistent estimates of aboveground net biomass change (∆AGB) are needed. Countries with limited forest monitoring capabilities in the tropics and subtropics rely on IPCC 2006 default ∆AGB rates, which are values per ecological zone, per continent. Similarly, research into forest biomass change at a large scale also makes use of these rates. IPCC 2006 default rates come from a handful of studies, provide no uncertainty indications and do not distinguish between older secondary forests and old-growth forests. As part of the 2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories, we incorporate ∆AGB data available from 2006 onwards, comprising 176 chronosequences in secondary forests and 536 permanent plots in old-growth and managed/logged forests located in 42 countries in Africa, North and South America and Asia. We generated ∆AGB rate estimates for younger secondary forests (≤20 years), older secondary forests (>20 years and up to 100 years) and old-growth forests, and accounted for uncertainties in our estimates. In tropical rainforests, for which data availability was the highest, our ∆AGB rate estimates ranged from 3.4 (Asia) to 7.6 (Africa) Mg ha-1  year-1 in younger secondary forests, from 2.3 (North and South America) to 3.5 (Africa) Mg ha-1  year-1 in older secondary forests, and 0.7 (Asia) to 1.3 (Africa) Mg ha-1  year-1 in old-growth forests. We provide a rigorous and traceable refinement of the IPCC 2006 default rates in tropical and subtropical ecological zones, and identify which areas require more research on ∆AGB. In this respect, this study should be considered as an important step towards quantifying the role of tropical and subtropical forests as carbon sinks with higher accuracy; our new rates can be used for large-scale GHG accounting by governmental bodies, nongovernmental organizations and in scientific research.

NCCN Guidelines Insights: B-Cell Lymphomas, Version 3.2019.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin's lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

Introduction of Community-Based Provision of Subcutaneous Depot Medroxyprogesterone Acetate (DMPA-SC) in Benin: Programmatic Results.

The Republic of Benin faces high maternal, newborn, and child mortality; low modern contraceptive use; and a critical shortage of health workers. In 2013, the Government of Benin made 3 reproductive health commitments to improve national health indicators, including expanding provision of family planning services at the community level through task sharing. Since 2016, the Advancing Partners & Communities (APC) project has been helping the Benin Ministry of Health (MOH) provide subcutaneous depot medroxyprogesterone acetate (DMPA-SC; brand name Sayana Press) through facility-based health care providers and community health workers known as relais communautaires (RCs). DMPA-SC is an easy-to-administer, discreet injectable contraceptive that provides 3 months of protection from pregnancy. Beginning in May 2017, the government introduced DMPA-SC through a phased approach in 10 health zones, which encompassed 149 health centers and 614 villages. Between June 2017 and June 2018, the MOH and APC trained 278 facility-based providers and 917 RCs to provide DMPA-SC, and nearly 11,000 doses were subsequently administered to 7,997 women at facilities and in communities. This article presents findings from an assessment of community-level and health facility service data collected during the first 13 months of DMPA-SC introduction in Benin. Because of this intervention, nearly 35,000 women received family planning counseling and 7,997 women chose DMPA-SC. At the community level, 3,111 DMPA-SC users were first-time users of modern contraception. The initial success of the DMPA-SC rollout in Benin shows promise for helping the country meet its reproductive health commitments.

Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma.

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A, USP7, and CHD8, we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.

Follicular Dendritic Cell Sarcoma With Indolent T-Lymphoblastic Proliferation Is Associated With Paraneoplastic Autoimmune Multiorgan Syndrome.

Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT. Chart review was performed to characterize the clinical behavior including evidence of autoimmune disease. FDCS occurred in a wide variety of nodal and extranodal sites. Fourteen of 31 (45%) cases contained immature TdT-positive T cells; in 5 cases these cells were numerous and present throughout the tumor. Four of these 5 patients with numerous immature T cells developed autoimmune disease, clinically categorized as PAMS and/or myasthenia gravis. PAMS persisted after tumor resection, causing severe morbidity and mortality. These findings suggest that the neoplastic follicular dendritic cells can recruit or foster the proliferation of immature T cells and that these cells may play a role in mediating PAMS. Recognition of iT-LBP in FDCS is important to avoid misdiagnosis as thymoma or T-lymphoblastic lymphoma, and may predict serious autoimmune complications in some patients.

Classifying drivers of global forest loss.

Global maps of forest loss depict the scale and magnitude of forest disturbance, yet companies, governments, and nongovernmental organizations need to distinguish permanent conversion (i.e., deforestation) from temporary loss from forestry or wildfire. Using satellite imagery, we developed a forest loss classification model to determine a spatial attribution of forest disturbance to the dominant drivers of land cover and land use change over the period 2001 to 2015. Our results indicate that 27% of global forest loss can be attributed to deforestation through permanent land use change for commodity production. The remaining areas maintained the same land use over 15 years; in those areas, loss was attributed to forestry (26%), shifting agriculture (24%), and wildfire (23%). Despite corporate commitments, the rate of commodity-driven deforestation has not declined. To end deforestation, companies must eliminate 5 million hectares of conversion from supply chains each year.

Primary Bone Lymphoma Exhibits a Favorable Prognosis and Distinct Gene Expression Signatures Resembling Diffuse Large B-Cell Lymphoma Derived From Centrocytes in the Germinal Center.

Primary bone (PB) diffuse large B-cell lymphoma (DLBCL) is rare and has a favorable prognosis, but the underlying biological mechanisms remain unknown. In this study we analyzed the clinicopathologic features of 160 patients with PB-DLBCL in comparison with 499 nonosseous DLBCL. Compared with patients with nonosseous DLBCL and secondary involvement of bone by DLBCL, PB-DLBCL patients less frequently had elderly age, B-symptoms, elevated serum lactate dehydrogenase levels, and high International Prognostic Index at diagnosis, more frequently had germinal center (GC) subtype (approximately 90%) and complete remission, and had significantly better survival. The 5-year progression-free and overall survival rates of PB-DLBCL patients were 80% and 93%, respectively, superior to both GC B-cell-like (GCB) and activated B cell-like subtypes of DLBCL. Further stratifying nonosseous DLBCL cell-of-origin subtypes by clinical factors showed that PB-DLBCL had similar survival rates as the centrocyte-origin (CC) subtype of DLBCL-GCB classified by the B-cell-associated gene signature algorithm. To better understand the favorable outcome of PB-DLBCL patients, gene expression profiling and microRNA profiling were performed in a small subset of PB-DLBCL. The gene expression profiles of PB-DLBCL resembled those of nonosseous DLBCL-GCB-CC, but were distinct from other DLBCL cell-of-origin especially the centroblast-origin (CB) subtype. Compared with DLBCL-GCB-CB, PB-DLBCL and DLBCL-GCB-CC also had much higher levels of miR-125a-3p, miR-34-3p, and miR-155-5p, and significantly lower levels of miR-17-5p and miR-17-3p. These results demonstrated that PB-DLBCL is clinically distinct, and the cell-of-origin of PB-DLBCL stems from centrocytes in the GC, that are biologically attributed for the favorable prognosis of PB-DLBCL.

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017.

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL.

Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.