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1.
Eur J Surg Oncol ; 50(1): 107298, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38086314

RESUMO

BACKGROUND: Histologic subtype of cancer guides treatment sequencing and the extent of surgery for retroperitoneal tumours (RPTs) but concerns persist regarding percutaneous core needle biopsy (CNB). OBJECTIVE: Endpoints were the incidence of early complications, needle tract seeding (NTS) after CNB, diagnostic accuracy. METHODS: Between 2015 and 2022, data from patients with RPT who underwent a CNB and who operated on at Institut Curie were collected. We retrospectively reviewed the medical records and microscopic analysis of both CNB and surgical specimens to evaluate the diagnostic accuracy of CNB (quantified using positive and negative predictive values, PPV/NPV). RESULTS: 313 patients underwent CNB. In 10/326 (3 %) procedures, minor complications were observed. One of 212 (0.47 %) resected RPSs exhibited a local recurrence compatible with NTS. Microscopic analysis of CNB specimens allowed the classification of tumours between groups of cancers and benign/intermediate mesenchymal tumours in 307/313 (98 %) patients. Among the 204 patients with retroperitoneal sarcoma, the overall concordance between CNB and final pathology following resection was 178/204 (87.2 %). The respective PPVs of solitary fibrous tumour, dedifferentiated liposarcoma, leiomyosarcoma and well-differentiated liposarcoma were 100 %, 98 %, 97 % and 68 %, respectively. The diagnosis of a high-grade (G 2-3) sarcoma resulted in a high specificity (97 %) and PPV (98 %) but low sensitivity (76 %). CONCLUSIONS: CNB allowed the classification of RPT in the vast majority of patients with a low morbidity rate. Concordance with final diagnosis was high for sarcomas with the exception of well-differentiated liposarcoma. As a result, CNB results should be integrated with imaging/radiomics by multidisciplinary tumour boards.


Assuntos
Lipossarcoma , Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Sarcoma/cirurgia , Lipossarcoma/patologia , Neoplasias de Tecidos Moles/patologia
2.
Cancers (Basel) ; 15(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37958366

RESUMO

Kidney cancer accounts for 3% of adult malignancies and is increasingly detected through advanced imaging techniques, highlighting the need for effective treatment strategies. This retrospective study assessed the safety and efficacy of a new single-probe percutaneous cryoablation system using liquid nitrogen for treating T1a renal cancers. From May 2019 to May 2022, 25 consecutive patients from two academic hospitals, with a median age of 64.8 years [IQR 59; 75.5], underwent cryoablation for 26 T1a renal tumors. These tumors had a median size of 25.3 mm [20; 30.7] and a median RENAL nephrometry score, indicating tumor complexity, of 7 [5; 9]. No major complications arose, but three non-clinically relevant perirenal hematomas were detected on post-procedure CT scans. With a median follow-up of 795 days [573; 1020], the primary local control rate at one month stood was 80.8% (21 out of 26). The five recurrent lesions, which exhibited a higher renal score (p = 0.016), were treated again using cryoablation, achieving a secondary local control rate of 100%. No patient died, and the disease-free survival rate was 92% (23 out of 25). In conclusion, single-probe percutaneous cryoablation emerges as a promising modality for managing small renal masses. Notably, recurrence rates appear influenced by RENAL nephrometry scores, suggesting a need for further research to refine the technique.

3.
Int J Part Ther ; 10(1): 59-64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37823017

RESUMO

Purpose: The exposition of cardiac conduction system during breast radiation therapy has never been studied, despite the increasing use of intensity-modulated radiation therapy, which exposes larger volume to low-dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy and estimated the potential dosimetric benefit with intensity-modulated proton therapy. Materials and Methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation computed tomography scans of 12 breast cancer patients having undergone conserving surgery and adjuvant locoregional volumetric modulated arc therapy. Intensity-modulated proton therapy treatment was replanned on the simulation computed tomography scans for all breast cancer patients. Mean and maximum doses delivered to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and the whole heart. Results: Average mean doses delivered to the SAN and AVN were 2.8 and 2.3 Gy, respectively, for left-sided irradiation and 9.6 and 3.6 Gy, respectively, for right-sided irradiation. Average maximum doses to the SAN and AVN were 3.5 Gy and 2.8 Gy, respectively, for left-sided irradiation and 13.1 and 4.6 Gy, respectively, for right-sided irradiation. Intensity-modulated proton therapy significantly reduced mean and maximum doses to the SAN and AVN. Correlations between doses to the SAN or AVN and whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast volumetric modulated arc therapy, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac-sparing techniques, such as respiratory techniques or proton therapy, which could benefit patients with underlying rhythmic or conduction disorders.

4.
Cancers (Basel) ; 15(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37627186

RESUMO

INTRODUCTION: Predictive biomarkers associated with pathological response, progression precluding surgery, and/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR0) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. METHODS: Consecutive patients with resectable stage IB (≥4 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR0 and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). RESULTS: Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3-60.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR0 cutoff of 30%/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01-0.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03-0.7; p = 0.01). The TGR0 cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64-0.95) and 0.80 (95% CI, 0.62-0.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6-289.1; p = 0.006). CONCLUSIONS: Assessment of TGR0 can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.

5.
Br J Cancer ; 129(5): 772-781, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37443346

RESUMO

BACKGROUND: The immune landscape of uveal melanoma liver metastases (UMLM) has not been sufficiently studied. METHODS: Immune cell infiltrates (ICIs), PD-1 and PD-L1 were characterised in 62 UMLM and 28 primary uveal melanomas (PUM). ICI, PD-1 and PD-L1 were scored as: (1) % tumoral area occupied by tumour-infiltrating lymphocytes or macrophages (TILs, TIMs) and (2) % perTumoral (perT) area. ICIs and other variables including histopathologic growth patterns (HGPs), replacement and desmoplastic, of UMLM were analysed for their prognostic value. RESULTS: ICIs recognised by haematoxylin-eosin-saffron (HES) and IHC (e.g., T cells (CD3), B cells (CD20). Macrophages (CD68), (CD163), were primarily localised to the perT region in PUM and UMLM and were more conspicuous in UMLM. HES, CD3, CD4, FoxP3, CD8, CD20, PD-1 TILs were scant (<5%). TIMs were more frequent, particularly in UMLM than in PUM. Both CD68+ TIMs and HGPs remained significant on multivariate analysis, influencing overall (OS) and metastasis-specific overall survival (MSOS). CD68 + , CD163+ and CD20+ perT infiltrates in UMLM predicted increased OS and MSOS on univariate analysis. CONCLUSIONS: TILs and PD-L1 have no predictive value in PUM or UMLM. CD68+ and CD163+TIMs, CD20+ perT lymphocytes, and HGPs are important prognostic factors in UMLMs.


Assuntos
Neoplasias Hepáticas , Melanoma , Humanos , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Melanoma/patologia , Neoplasias Hepáticas/patologia , Linfócitos do Interstício Tumoral , Prognóstico , Biomarcadores Tumorais/análise
6.
Ann Surg ; 278(4): e827-e834, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36847256

RESUMO

OBJECTIVE: We report here the results of a prospective study of circulating tumor DNA (ctDNA) detection in patients undergoing uveal melanoma (UM) liver metastases resection (NCT02849145). BACKGROUND: In UM patients, the liver is the most common and often only site of metastases. Local treatments of liver metastases, such as surgical resection, have a likely benefit in selected patients. METHODS: Upon enrollment, metastatic UM patients eligible for curative liver surgery had plasma samples collected before and after surgery. GNAQ / GNA11 mutations were identified in archived tumor tissue and used to quantify ctDNA by droplet digital polymerase chain reaction which was then associated with the patient's surgical outcomes. RESULTS: Forty-seven patients were included. Liver surgery was associated with a major increase of cell-free circulating DNA levels, with a peak 2 days after surgery (∼20-fold). Among 40 evaluable patients, 14 (35%) had detectable ctDNA before surgery, with a median allelic frequency of 1.1%. These patients experienced statistically shorter relapse-free survival (RFS) versus patients with no detectable ctDNA before surgery (median RFS: 5.5 vs 12.2 months; hazard ratio=2.23, 95% CI: 1.06-4.69, P =0.04), and had a numerically shorter overall survival (OS) (median OS: 27.0 vs 42.3 months). ctDNA positivity at postsurgery time points was also associated with RFS and OS. CONCLUSIONS: This study is the first to report ctDNA detection rate and prognostic impact in UM patients eligible for surgical resection of their liver metastases. If confirmed by further studies in this setting, this noninvasive biomarker could inform treatment decisions in UM patients with liver metastases.


Assuntos
DNA Tumoral Circulante , Neoplasias Hepáticas , Humanos , DNA Tumoral Circulante/genética , Prognóstico , Estudos Prospectivos , Recidiva Local de Neoplasia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Biomarcadores Tumorais/genética , Mutação
8.
Ann Surg Oncol ; 30(2): 943-953, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36287348

RESUMO

BACKGROUND: Unlike for soft tissue sarcomas, percutaneous biopsy is not validated for uterine myometrial tumors, leading to leiomyosarcoma inadvertent morcellation and overtreatment in childbearing patients. This study aimed to evaluate preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-comparative genomic hybridization (MCGH-PUB). METHODS: This was a prospective single-center cohort study including all consecutive patients who were candidates for hysterectomy because of suspected uterine leiomyosarcoma on magnetic resonance imaging (MRI) who received PUB. Microscopic and array-CGH analyses with genomic index (GI) counts were performed to guide the therapeutic strategy. Smooth-muscle tumors with suspect features with a GI above 15 were deemed malignant, as were tumors without microscopic malignant features with a complex genomic profile (GI above 30 or malignant profile). Preoperative diagnoses based on M-PUB and MCGH-PUB were compared with the postsurgical pathological specimen or follow-up. RESULTS: From November 2016 to February 2022, 34 patients were included. Based on the surgical specimen (N = 23) or follow-up (N = 11), final diagnoses were 11 sarcomas and 23 non-sarcomas. The median follow-up was 12 months (IQR 6-37). The diagnostic accuracies of M-PUB and MCGH-PUB were 94% and 100%, respectively. The sensitivity, specificity, and negative predictive value of MCGH-PUB were 100%, 100%, and 100%, respectively. A high GI was significantly associated with malignancy (P < 0.001). Genomic analyses allowed malignancy upgrades for four tumors. There were no complications and no dissemination along the biopsy track. CONCLUSION: MCGH-PUB is safe and accurate for preoperatively diagnosing uterine sarcomas and should be used routinely after suspicious MRI to tailor surgery.


Assuntos
Leiomiossarcoma , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/cirurgia , Projetos Piloto , Estudos Prospectivos , Estudos de Coortes , Hibridização Genômica Comparativa , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/cirurgia , Biópsia por Agulha/métodos , Imageamento por Ressonância Magnética/métodos
9.
NPJ Precis Oncol ; 6(1): 81, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323843

RESUMO

Inactivating mutations of MBD4 have been reported in subsets of various tumors. A deficiency of this DNA glycosylase, recognizing specifically T:G mismatch resulting from the deamination of methyl-cytosine, results in a hypermutated phenotype due to the accumulation of CpG>TpG transitions. Here, we hypothesize that the difference in DNA metabolism consecutive to MBD4 deficiency may result in specific cytotoxicities in MBD4-deficient tumor cells in a synthetic lethality fashion. After a large-scale drug repurposing screen, we show in two isogenic MBD4 knock-out cell models that the inactivation of MBD4 sensitizes cancer cells to cytidine analogs. We further confirm the exquisite activity of gemcitabine in an MBD4-deficient co-clinical model as (i) it completely prevented the development of an MBD4-deficient uveal melanoma patient-derived xenograft and (ii) treatment in the corresponding patient resulted in an exceptional tumor response. These data suggest that patients harboring MBD4-deficient tumors may be treated efficiently by cytidine analogs.

11.
Oncoimmunology ; 11(1): 2116845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092639

RESUMO

Although combined PD-1/CTLA-4 inhibition showed limited efficacy in single-arm, phase II trials in metastatic uveal melanoma (mUM), such combination appears frequently used in mUM patients. We here report our experience with nivolumab/ipilimumab in mUM. A retrospective cohort of 47 mUM patients, 24 men and 23 women, received nivolumab/ipilimumab between October 2019 and December 2021, mostly first line (94%). Two regimens were used: nivolumab 1 mg/kg + ipilimumab 3 mg/kg (nivo1ipi3, 49% of patients) and nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo3ipi1, 51% of patients). Median follow-up was 37 and 88 weeks in nivo3ipi1 and nivo1ipi3 cohorts, respectively. We observed partial response in two patients (4%) and stable disease in 14 patients (30%), with no significant difference between the two regimens. Median progression-free survival was 13.6 weeks and 11.9 weeks in the nivo1ipi3 and nivo3ipi1 cohorts, respectively (p = 0.49). Severe adverse events (grade 3 or 4) were observed in seven patients (15%) among which five treated with nivo1ipi3 (22%) and two treated with nivo3ipi1 (8%). These data suggest that nivolumab/ipilimumab combination does not improve clinical outcomes compared to other therapies but is more toxic. In the absence of controlled clinical trials, we would not recommend this combination as a standard treatment in all mUM patients but rather as an option. Patients for whom the benefit-risk ratio could justify the combination need to be defined.


Assuntos
Segunda Neoplasia Primária , Nivolumabe , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Ipilimumab/uso terapêutico , Masculino , Melanoma , Segunda Neoplasia Primária/induzido quimicamente , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Neoplasias Uveais
12.
Ann Surg Oncol ; 29(13): 8480-8491, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35980554

RESUMO

BACKGROUND: Surgical management of liver metastases of uveal melanoma (LMUM) is associated with the best survival rates, especially for patients with a low tumor burden in the liver. The aim was to determine whether the tumor growth rate (TGR0) before liver resection helps predict survival in patients with resectable LMUM. METHODS: This retrospective study included 99 patients with LMUM treated with liver resection between November 2007 and November 2020. TGR0 was expressed as the percentage change in tumor volume over 1 month according to two pretreatment imaging scans. Multivariate Cox analyses identified independent predictors of disease-free survival (DFS) and overall survival (OS). RESULTS: DFS and OS had a statistically significant positive linear relationship (Spearman correlation r = 0.68, p < 0.001). A disease-free interval (DFI) > 24 months and a TGR0 ≤ 50%/month were independent factors associated with better DFS and OS. The 2-component model including TGR0 and DFI had a mean time-dependent area under the curve (AUC) of 0.81 (95% CI, 0.75-0.86) and 0.77 (95% CI, 0.67-0.87), respectively, for predicting DFS and OS. DFI with TGR0 defined three kinetic risk groups that had distinct DFS and OS outcomes (p < 0.001). Cytogenetic alterations at baseline were partially predictive factors of the kinetic risk score based on TGR0 and DFI. DISCUSSION: The assessment of TGR0 improves prognostic stratification by identifying patients at high risk of recurrence and poor survival after liver resection. TGR0 and DFI, reflecting tumor aggressivity, have the potential to be important markers for systemic adjuvant decisions.


Assuntos
Neoplasias Hepáticas , Neoplasias Uveais , Humanos , Estudos Retrospectivos , Neoplasias Uveais/cirurgia , Neoplasias Hepáticas/secundário , Prognóstico , Intervalo Livre de Doença , Taxa de Sobrevida
13.
Int J Radiat Oncol Biol Phys ; 114(3): 422-432, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35850363

RESUMO

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.


Assuntos
Antineoplásicos , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Antineoplásicos/uso terapêutico , Humanos , Terapia Neoadjuvante , Qualidade de Vida , Compostos Radiofarmacêuticos/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia
14.
Eur J Cancer ; 173: 105-112, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35863105

RESUMO

BACKGROUND: MBD4 mutations have been reported in uveal melanomas, acute myeloid leukemias, colorectal adenocarcinomas, gliomas, and spiradenocarcinomas and cause a hypermutated phenotype. Although metastatic uveal melanomas (mUM) are usually resistant to immune checkpoint inhibitors (ICI), the first reported MBD4-mutated (MBD4m) patient responded to ICI, suggesting that MBD4 mutation may predict response to ICI. METHODS: Retrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients. RESULTS: Three hundred mUM patients were included. Median follow-up was 17.3 months. Ten patients with an objective response and 20 cases with stable disease for >12 months were observed, corresponding to an objective response rate of 3.3% and a clinical benefit (i.e., responder patients and stable disease) rate of 10%. Of the 131 tumors sequenced for MBD4, five (3.8%) were mutated. MBD4 mutation was associated with a better objective response rate as three out of five MBD4m versus 4% of MBD4 wild-type patients responded (p < 0.001). Of these five responders, three presented progressive disease at 2.8, 13.9, and 22.3 months. Median PFS was 4.0 months in MBD4 wild-type and 22.3 months in MBD4m patients (HR = 0.22; p = 0.01). Median OS in MBD4def patients was unreached as compared to 16.6 months in MBD4pro (HR = 0.11; 95% CI: 0.02-0.86; log-rank p-test = 0.04; Fig. 2e). CONCLUSIONS: In mUM patients, MBD4 mutation is highly predictive for the response, PFS, and overall survival benefit to ICI. MBD4 could be a tissue-agnostic biomarker and should be sequenced in mUM, and other tumor types where MBD4 mutations are reported.


Assuntos
Endodesoxirribonucleases , Inibidores de Checkpoint Imunológico , Melanoma , Neoplasias Uveais , Endodesoxirribonucleases/genética , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Metástase Neoplásica , Estudos Retrospectivos , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/genética
15.
Lab Invest ; 102(11): 1214-1224, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35672380

RESUMO

The replacement histopathologic growth pattern (rHGP) in melanoma liver metastases connotes an aggressive phenotype (vascular co-option; angiotropic extravascular migratory spread) and adverse prognosis. Herein, replacement and desmoplastic HGP (dHGP) were studied in uveal melanoma liver metastases (MUM). In particular, L1CAM and a "laminin vascular network" were detected at the advancing front of 14/20 cases (p = 0.014) and 16/20 cases (p = 6.4e-05) rHGPs, respectively, but both were absent in the dHGP (8/8 cases) (p = 0.014, and p = 6.3e-05, respectively). L1CAM highlighted progressive extension of angiotropic melanoma cells along sinusoidal vessels in a pericytic location (pericytic mimicry) into the hepatic parenchyma. An inverse relationship between L1CAM expression and melanin index (p = 0.012) suggested differentiation toward an amelanotic embryonic migratory phenotype in rHGP. Laminin labeled the basement membrane zone interposed between sinusoidal vascular channels and angiotropic melanoma cells at the advancing front. Other new findings: any percentage of rHGP and pure rHGP had a significant adverse effect on metastasis-specific overall survival (p = 0.038; p = 0.0064), as well as predominant rHGP (p = 0.0058). Pure rHGP also was associated with diminished metastasis-free survival relative to dHGP (p = 0.040), possibly having important implications for mechanisms of tumor spread. In conclusion, we report for the first time that L1CAM and a laminin vascular network are directly involved in this high-risk replacement phenotype. Further, this study provides more detailed information about the adverse prognostic effect of the rHGP in MUM.


Assuntos
Neoplasias Hepáticas , Melanoma , Molécula L1 de Adesão de Célula Nervosa , Neoplasias Uveais , Humanos , Laminina , Melaninas , Melanoma/metabolismo
16.
Cancers (Basel) ; 14(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35565242

RESUMO

SF3B1 mutations are recurrent in cancer and result in aberrant splicing of a previously defined set of genes. Here, we investigated the fate of aberrant transcripts induced by mutant SF3B1 and the related functional consequences. We first demonstrate that mutant SF3B1 does not alter global nascent protein synthesis, suggesting target-dependent consequences. Polysome profiling revealed that 35% of aberrantly spliced transcripts are more translated than their corresponding canonically spliced transcripts. This mostly occurs in genes with enriched metabolic functions. Furthermore, LC-MS/MS analysis showed that mutant SF3B1 impacts the abundance of proteins involved in metabolism. Functional metabolic characterization revealed that mutant SF3B1 decreases mitochondrial respiration and promotes glycolysis to compensate for defective mitochondrial metabolism. Hence, mutant SF3B1 induces glycolysis dependency, which sensitizes cells to glycolysis inhibition. Overall, we provide evidence of the oncogenic involvement of mutant SF3B1 in uveal melanoma through a metabolic switch to glycolysis, revealing vulnerability to glycolysis inhibitors as a promising therapeutic strategy.

17.
Br J Cancer ; 127(2): 258-267, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35347325

RESUMO

BACKGROUND: The RECIST-based response variably matches the clinical benefit of systemic therapies for liver metastatic uveal melanoma (LMUM). The aims were to determine whether the tumour growth rate (TGR) can help predict the survival in patients with LMUM and to provide information for the management of first-line systemic treatment. METHODS: This retrospective study included 147 (training: n = 110, validation: n = 37) patients with LMUM treated with first-line systemic treatment between 2010 and 2021. Two TGR-derived parameters were calculated, TGR0 and TGR3m. Multivariate Cox analyses identified independent predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: TGR3m was a strong independent prognostic factor of PFS and OS (p < 0.001). The RECIST-based response was no longer significant in the OS analyses. Only immunotherapy regimens correlated with higher OS (HR = 0.2; 95% CI, 0.1-0.5; p < 0.001) in the low-TGR3m (≤50%/m) subgroup. These findings were confirmed in the validation cohort. TGR0, disease-free interval (DFI), and the sum of target lesions at baseline were predictive factors of low TGR3m. DISCUSSION: The use of TGR3m would improve tumour assessment by identifying patients who would benefit from first-line immunotherapy regimens despite PD. TGR0, DFI and the sum of target lesions were correlated with TGR3m, which can support first-line treatment decision-making for immunotherapy.


Assuntos
Melanoma , Segunda Neoplasia Primária , Humanos , Imunoterapia , Fígado/patologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Estudos Retrospectivos , Neoplasias Uveais
18.
Radiother Oncol ; 170: 55-63, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35307485

RESUMO

Several randomized controlled trials have demonstrated the benefit of a boost to the tumor bed (TB) to reduce the risk of ipsilateral breast tumor recurrence. Recent technological progress has facilitated improved conformation of isodoses around the target volume. The accuracy and reproducibility of TB delineation have become even more essential. The purpose of this study is to review the extant knowledge on the boost delineation in breast cancer, focusing on interobserver variability (IOV) and the influence of various factors, such as the presence of clips or different imaging modalities to improve IOV. Most studies investigating IOV for boost delineation have shown poor reproducibility (with comparison indices such as the dice similarity index around 0.5). Clips in the lumpectomy cavity (LC), postoperative fluid accumulation in the LC and/or high cavity visualization score appeared to be associated with improved IOV. Likewise, the use of preoperative imaging (CT and/or MRI) may also be useful in improving the accuracy of TB definition but without any real gain in terms of IOV. Moreover, the delineation of boost has become even more challenging since the development of oncoplastic surgery. To improve the reproducibility and the accuracy of boost delineation, this review suggests that within each center, a group of multidisciplinary experts, including surgeons, radiation oncologists, pathologists, and radiologists, should convene to develop local guidelines, which may include the choice of preoperative imaging, the number and location of surgical clips, pathological margins, and orientation. The elaboration of contouring atlas is certainly of great assistance.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/patologia , Feminino , Humanos , Mastectomia Segmentar/métodos , Variações Dependentes do Observador , Planejamento da Radioterapia Assistida por Computador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
19.
Pract Radiat Oncol ; 12(6): 533-538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35192938

RESUMO

PURPOSE: There is increasing evidence that radiation doses to cardiac substructures are associated with cardiac adverse events. Manual delineation of cardiac substructures is time-consuming, and auto-segmentation of cardiac substructure atlases has consequently been evaluated. However, proper automatic delineation of small substructures, such as the left anterior descending coronary artery, is challenging, and auto-segmentation of cardiac conduction system substructures has never been evaluated, despite multiple reports of radiation-induced arrhythmia after thoracic irradiations. The aim of this study was to propose and evaluate a simplified auto-segmentable functional cardiac atlas. METHODS AND MATERIALS: We created a cardiac substructure atlas based on 20 computed tomography scans from patients with breast cancer comprising the 4 cardiac cavities, a high-risk cardiac zone as a left anterior descending coronary artery surrogate, and the 2 cardiac conduction nodes. Automatic delineation of this atlas by an atlas-based auto-segmentation algorithm was evaluated on a validation data set, consisting of 20 additional computed tomography scans. Dice similarity coefficients were used to evaluate the concordance level between the manual and the automatic contours; a dosimetric comparison between mean and maximum doses to the manual and to the auto-segmented substructures was additionally performed, based on intensity modulated radiation therapy treatment plans of the patients of the validation set. RESULTS: Average dice similarity coefficient values were 0.78 for the 4 cardiac cavities, 0.65 for the high-risk cardiac zones, 0.56 for the sinoatrial node, and 0.15 for the atrioventricular node. Compared with manual contours, auto-segmented substructures were slightly smaller but the dosimetric parameters were similar. CONCLUSIONS: We proposed a simplified functional cardiac atlas that included the cardiac conduction system and circumvented coronary delineation difficulties by using a surrogate high-risk cardiac zone. Most cardiac substructures were associated with acceptable atlas-based auto-segmentation properties. Such an atlas could be used for epidemiologic studies and for clinical practice.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Coração/diagnóstico por imagem , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Órgãos em Risco
20.
Cardiovasc Intervent Radiol ; 45(2): 244-248, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34853875

RESUMO

OBJECTIVES: The purpose of this retrospective observational study is to report author's experience in computed-tomography (CT)-guided percutaneous vertebroplasty (PV) of the cervicothoracic junction. METHODS: The records of all consecutive patients treated by PV at levels C7, T1, T2, and T3 in a tertiary cancer center during year 2020 were extracted from the Institutional electronic archive. Following data were collected: demographics, indication for PV, procedure features, outcomes, and complications. Technical success was defined as when the trocar was placed into the vertebral body, allowing the injection of polymethyl-metacrylate (PMMA). RESULTS: Eleven patients were identified who received PV on 14 levels. Mean procedure duration was 57 ± 22 min (range [31-142]). A "trans-pedicular approach at the targeted level" was used in 1 vertebra (7%), a "costotransverse approach, at the targeted level" was used in 1 vertebra (7%), a "transpedicular approach via the level below" was used in 3 vertebrae (22%), and a "costotransverse approach via the level below" was used in 9 vertebrae (64%). Meantime to deploy each trocar was 20 ± 5 min (range [12-32]). Technical success was achieved in 14/14 (100%) of vertebrae. Mean postoperative hospitalization duration was 1.9 ± 1.7 days (range [1-11]). According to CIRSE classification, no adverse event occurred. PMMA leakage occurred in two patients; both remained asymptomatic. CONCLUSION: This study provides arguments in favor of safety and efficiency of CT-guided vertebroplasty of levels C7, T1, T2, and T3, for both trocar deployment and monitoring of the vertebral body filling during the PMMA injection.


Assuntos
Fraturas Espontâneas , Neoplasias , Fraturas da Coluna Vertebral , Vertebroplastia , Cimentos Ósseos/uso terapêutico , Humanos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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