KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study

Background: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. Patients and methods: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. Results: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. Conclusion: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib

A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl)

[Background] Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients.[Methods] URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.[Results] In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).[Conclusions] This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.This work was supported by the Carisbo Foundation Call for Translational and Clinical Medical Research.Peer reviewe

Time Efficient Dual-Field Unit for Cryptography-Related Processing

International audienceComputational demanding public key cryptographic algorithms, such as Rivest-Shamir-Adleman (RSA) and Elliptic Curve (EC) cryptosystems, are critically dependent on modular multiplication for their performance. Modular multiplication used in cryptography may be performed in two different algebraic structures, namely GF(N) and GF(2n), which normally require distinct hardware solutions for speeding up performance. For both fields, Montgomery multiplication is the most widely adopted solution, as it enables efficient hardware implementations, provided that a slightly modified definition of modular multiplication is adopted. In this paper we propose a novel unified architecture for parallel Montgomery multiplication supporting both GF(N) and GF(2n) finite field operations, which are critical for RSA ad ECC public key cryptosystems. The hardware scheme interleaves multiplication and modulo reduction. Furthermore, it relies on a modified Booth recoding scheme for the multiplicand and a radix-4 scheme for the modulus, enabling reduced time delays even for moderately large operand widths. In addition, we present a pipelined architecture based on the parallel blocks previously introduced, enabling very low clock counts and high throughput levels for long operands used in cryptographic applications. Experimental results, based on 0.18 μm CMOS technology, prove the effectiveness of the proposed techniques, and outperform the best results previously presented in the technical literature

Time Efficient Dual-Field Unit for Cryptography-related Processing

Computational demanding public key cryptographic algorithms, such as RivestShamir-Adleman (RSA) and Elliptic Curve (EC) cryptosystems, are critically dependent on modular multiplication for their performance. Modular multiplication used in cryptography may be performed in two different algebraic structures, namely GF (N ) and GF (2 n ), which normally require distinct hardware solutions for speeding up performance. For both fields, Montgomery multiplication is the most widely adopted solution, as it enables efficient hardware implementations, provided that a slightly modified definition of modular multiplication is adopted. In this paper we propose a novel unified architecture for parallel Montgomery multiplication supporting both GF (N ) and GF (2 n ) finite field operations, which are critical for RSA ad ECC public key cryptosystems. The hardware scheme interleaves multiplication and modulo reduction. Furthermore, it relies on a modified Booth recoding scheme for the multiplicand and a radix-4 scheme for the modulus, enabling reduced time delays even for moderately large operand widths. In addition, we present a pipelined architecture based on the parallel blocks previously introduced, enabling very low clock counts and high throughput levels for long operands used in cryptographic applications. Experimental results, based on 0.18µm CMOS technology, prove the effectiveness of the proposed techniques, and outperform the best results previously presented in the technical literature