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Planthoppers are an interesting and contrasting model among insects for studying the subterranean environments. Their morphological and ethological adaptations to the underground conditions (complete darkness, lower temperatures, high hygrometry, stability of environmental constants, rarefied food sources, etc.), and their worldwide distribution in both temperate and tropical areas make them an interesting model among invertebrates. In this review, we highlight why cave planthoppers study matters, with particular emphasis on the Cixiidae. The two hypotheses proposed, the ‘climatic relict hypothesis’ and the ‘adaptive shift’, are not sufficient enough to clearly understand and explain the drivers to cavernicoly. Phylogenetic analyses approaches might help to better document and increase our knowledge on such peculiar environments. The singularity of the distribution pattern of the adaptation to cavernicoly in planthoppers raises also interesting questions to investigate and suggest contrasting scenarios to explore further, particularly should the Cixiidae be defined as a subtroglophile lineage?

The nine genera of Malagasy spittlebug are revised, with the addition of new characters, facilitating the identification of the species. Nesaulax Jacobi, 1917, is synonymized with Amberana Distant, 1908, leading to a new combination for Amberana vittipennis (Bergroth, 1894). A new endemic genus Soulierana Bucher & Bouteille gen. nov. is proposed for two species originally placed in Literna Stål, 1866, based on morphological characters of the head, tegmina and male genitalia. Also, three new species are described in this genus: Soulierana bigidea Bucher gen. et sp. nov., Soulierana claudinae Bouteille gen. et sp. nov. and Soulierana kelymena Le Cesne gen. et sp. nov. Pictures of species and drawings of the male genitalia for all genera, with the exception of Rhinaulax Amyot & Serville, 1843, Alluaudensia Lallemand, 1920 and Literna, are included. An identification key is available in both a dichotomous format and an interactive format (Xper3).

PurposeAntitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.MethodsSEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461).ResultsTwo hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001).ConclusionPatients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.

Background: Missing covariates are common in observational research and can lead to bias and loss of statistical power. Limited data regarding prognostic factors of survival outcomes of sarcomas in irradiated fields (SIF) are available. Because of the long lag time between irradiation of first cancer and scarcity of SIF, missing data are a critical issue when analyzing long-term outcomes. We assessed prognostic factors of overall (OS), progression-free (PFS), and metastatic-progression-free (MPFS) survivals in SIF using three methods to account for missing covariates. Methods: We relied on the NETSARC French Sarcoma Group database, Cox (OS/PFS), and competitive hazards (MPFS) survival models. Covariates investigated were age, sex, histological subtype, tumor size, depth and grade, metastasis, surgery, surgical resection, surgeon’s expertise, imaging, and neo-adjuvant treatment. We first applied multiple imputation (MI): observed data were used to estimate the missing covariate. With the missing-data modality approach, a category missing was created for qualitative variables. With the complete-case (CC) approach, analysis was restricted to patients without missing covariates. Results: CC subjects ( N = 167; 33%) presented more often with soft-tissue sarcoma ( versus visceral sarcoma) and grade I–II tumors as compared to the 504 eligible cases. With MI ( N = 504), factors associated with the worst outcome included metastasis ( p = 0.04) and R1/R2 resection ( p < 0.001) for OS; higher grade/non-gradable tumors ( p = 0.002) and R1/R2 resection ( p < 0.001) for PFS; and metastasis ( p = 0.01) for M-PFS. The ‘missing-data modality’ approach ( N = 504) led to different associations, including significance reached due to variables with the modality ‘missing’. The CC analysis led to different results and reduced precision. Conclusion: The CC population was not representative of the eligible population, introducing bias, in addition to worst precision. The ‘missing-data modality method’ results in biased estimates in non-randomized studies, as outcomes may be related to variables with missing values. Appropriate statistical methods for missing covariates, for example, MI, should therefore be considered.

Background: Leiomyosarcoma (LMS) and liposarcoma (LPS) are ultra-rare sarcomas in pediatric (0–18 years) and young adult (19−30) populations. We aimed to analyze their clinical characteristics at these young ages and to determine whether they should be considered with the same therapeutic strategy in both populations. Methods: National retrospective multicenter study of all young patients (0–30 years) included in the sarcoma database “ConticaBase”, treated for LMS or LPS between 2010 and 2019 via the national NETSARC+ network, with available pathology/biology review. Findings: A total of 218 patients were identified, 34 children (nine LMS, 25 LPS) and 184 young adults (58 LMS, 126 LPS). Myxoid/Round Cell LPS (M/RC-LPS) was the most frequent LPS subtype (72 %). All children had localized LMS and LPS, versus 52/58 and 116/126 respectively in adults. Clinical presentation of LMS and all LPS subtypes was comparable in both populations, except for a preferential limb location of LMS in children. The therapeutic strategy was mainly based on primary surgery in LMS (9/9 children, 52/58 adults) and for LPS (respectively 25/25 and 122/126), exclusively or with adjuvant radiotherapy and systemic treatment. With a median follow-up of 62.4 months (range, 2.5–146), 5-year overall survival was respectively 83 % [95 % CI, 58–100] in children and 73 % [61–88] in young adults for LMS, 100 % [100] vs 92 % [87–99] for M/RC-LPS and 25 % [5–100] vs 60 % [29–100] for pleomorphic LPS. Interpretation: LMS and all LPS subtypes appear to display comparable behavior in children and young adults. The authors propose that the same therapeutic strategy should be considered for both groups.

Abstract Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single‐agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single‐agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI‐CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1–6.5), and median OS was 9.9 months (95%CI: 6.6–13.4). Single‐agent gemcitabine has clinically meaningful activity in advanced, heavily pre‐treated angiosarcoma.

With the emergence of novel targeted therapeutic options in early-stage and advanced-stage malignancies, researchers have shifted their focus on developing personalized treatment plans through molecular profiling. Circulating tumor DNA (ctDNA) is a cell-free DNA (ctDNA) fragment, originating from tumor cells, and circulating in the bloodstream as well as biological fluids. Over the past decade, many techniques were developed for liquid biopsies through next-generation sequencing. This alternative non-invasive biopsy offers several advantages in various types of tumors over traditional tissue biopsy. The process of liquid biopsy is considered minimally invasive and therefore easily repeatable when needed, providing a more dynamic analysis of the tumor cells. Moreover, it has an advantage in patients with tumors that are not candidates for tissue sampling. Besides, it offers a deeper understanding of tumor burden as well as treatment response, thereby enhancing the detection of minimal residual disease and therapeutic guidance for personalized medicine. Despite its many advantages, ctDNA and liquid biopsy do have some limitations.This paper discusses the basis of ctDNA and the current data available on the subject, as well as its clinical utility. We also reflect on the limitations of using ctDNA in addition to its future perspectives in clinical oncology and precision medicine.

Abstract Background The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. Results Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p

Abstract Background Soft tissue sarcomas (STS) are heterogeneous and pro-metastatic tumors. Identification of accurate prognostic factors and novel therapeutic targets are crucial. CSPG4 is a cell surface proteoglycan with oncogenic functions. It recently emerged as a potential target for immunotherapy, including cell therapy based on CSPG4-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CSPG4-CAR.CIKs) in STS. However, expression of CSPG4 is poorly known in STS so far. Methods We analyzed CSPG4 gene expression in 1378 localized STS clinical samples, and searched for correlations with clinicopathological data, including disease-free survival (DFS), and with tumor immune features. Results CSPG4 expression was heterogeneous across samples. High expression was associated with younger patients’ age, more frequent undifferentiated pleomorphic sarcoma and myxofibrosarcoma pathological subtypes, more frequent internal trunk tumor site, and more CINSARC high-risk samples. No correlation existed with pathological tumor size and grade, and tumor depth. Patients with high CSPG4 expression displayed 49% (95% CI 42–57) 5-year DFS versus 61% (95% CI 56–68) in patients with low expression (p = 3.17E−03), representing a 49% increased risk of event in the “CSPG4-high” group (HR = 1.49, 95% CI 1.14–1.94). This unfavorable prognostic value persisted in multivariate analysis, independently from other variables. There were significant differences in immune variables between “CSPG4-high” and “CSPG4-low” tumors. The "CSPG4-low" tumors displayed profiles suggesting higher anti-tumor cytotoxic immune response and higher potential vulnerability to immune checkpoint inhibitors (ICI). By contrast, the "CSPG4-high" tumors displayed profiles implying an immune-excluded tumor microenvironment, potentially induced by hypoxia, resulting from an immature chaotic microvasculature, and/or the presence of contractile myofibroblasts. Conclusions Patients with “CSPG4-high” STS, theoretically candidate for CAR.CIKs, display shorter DFS and an immune environment unfavorable to vulnerability to CAR.CIKs, which could be improved by combining anti-angiogenic drugs able to normalize the tumor vasculature. By contrast, “CSPG4-low” STS are better candidates for immune therapy involving ICI.

A new planthoppers genus and species of Cixiidae Oecleini, Coframalaxius bletteryi gen. et sp. nov. newly discovered in a cave near Nice in southern France, is described. Molecular analysis confirms the morphology-based classification of Coframalaxius as sister to Trigonocranus within the Oecleni. Several morphological characters are further discussed. A double-grasping coxo-femoral and femoro-tibial system is regarded as apomorphic for the oecline taxa and would allow the nymph to firmly grab the roots and rootlets on which it feeds or use to progress in the soil. Wing vein patterns are discussed in the Cixiidae: 1) for the forewings, Oecleini belong to the trifid type of the anterior MP branch, leading to the reinterpretation of some recently described Neotropical species, 2) for the hindwing, four connection types (U-, V-, Y- and I-types) between MP and CuA are described. Oecleini belongs to I-type with a complete fusion of MP3+4 with CuA1. Although the area where the cave is located is well-studied with respect to its regularly sampled epigean fauna for many years, the taxon is new to science, highlighting its probable completely hypogean life cycle and leading to consider Coframalaxius bletteryi as an eutroglophile species.

Background: Desmoid type fibromatosis (DTF) are rare intermediate malignancies with unpredictable outcome. Series containing children and young adults (YA) are lacking. Methods: The aim of this retrospective study was to describe the French population of patients

Abstract Genomic instability (GI) influences treatment efficacy and resistance, and an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP “hotspotness” magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (transcription-associated chromosomal instability index) and iRACIN (replication-associated chromosomal instability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in Leiomyosarcoma (LMS) and that they may be combined to form a new classifier called MAGIC (mixed transcription- and replication-associated genomic instability classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.