VISTA/CTLA4/PD1 coexpression on tumor cells confers a favorable immune microenvironment and better prognosis in high-grade serous ovarian carcinoma.

Introduction: Immunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer. Methods: In this study, we investigated the expressions of VISTA, CTLA4, and PDL1 using immunohistochemistry (IHC)on 135 Formalin-Fixed Paraffin-Embedded (FFPE)tissue samples of High-grade serous carcinoma (HGSOC). VISTA, CTLA4, PDL1, PD1, CD8, CD4, and FOXP3 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort. Correlations between these checkpoints, tumor-infiltrating- lymphocytes (TILs), and survival were analyzed. Results and discussion: CTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression (p=0.04) correlated with overall survival (OS). Multivariate analyses showed that VISTA expression (p=0.01) and the coexpression of VISTA+/CTLA4+/PD1+ (p=0.05) were associated with better OS independently of the clinicopathological features. Kaplan-Meier analysis showed that the coexpression of the VISTA+/CTLA4+/PDL1+ and VISTA+/CTLA4+/PD1+ checkpoints on tumor cells (TCs)were associated with OS (p=0.02 and p<0.001; respectively). VISTA+/CTLA4+/PD1+ in TCs and CD4+/CD8+TILswere associated with better 2-yer OS. This correlation may refer to the role of VISTA as a receptor in the TCs and not in the immune cells. Thus, targeting combination therapy blocking VISTA, CTLA4, and PD1 could be a novel and attractive strategy for HGSOC treatment, considering the ambivalent role of VISTA in the HGSOC tumor cells.

HLA class II polymorphisms as prognostic biomarkers for right and left-sided colon cancer.

BACKGROUND: Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested. AIM OF THE STUDY: We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC. PATIENTS AND METHODS: Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP). RESULTS: DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC. CONCLUSION: DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC.

Primary adenocarcinoma of the upper esophagus: A rare presentation.

INTRODUCTION AND IMPORTANCE: Cervical esophageal cancer is a rare condition, accounting for less than 5 % of all esophageal malignancies. CASE PRESENTATION: We report here a case of a 65-year-old female patient with a history of breast cancer diagnosed in 1985 treated with surgery, adjuvant chemotherapy, and radiotherapy. This woman presented with chronic organic high dysphagia to both solid and liquids and food impaction. Gastroscopy showed a stenosing esophageal budding tumor located at 20 cm from the incisors. Histological examination showed a well-differentiated adenocarcinoma. CLINICAL DISCUSSION: The diagnosis of primary adenocarcinoma of the upper esophagus is based on a combination of clinical presentation, imaging studies, and confirmed by histopathological examination. Upper digestive endoscopy is the gold standard for the diagnosis of esophageal cancer. CONCLUSION: Primary adenocarcinoma of the upper esophagus is a rare form of esophageal cancer.

Assessing serum cytokine profiles in inflammatory breast cancer patients using Luminex® technology.

BACKGROUND: Inflammatory breast cancer (IBC), accounts for the majority of deaths associated with breast tumors. Because this form is aggressive from its appearance and has a strong metastatic potential. The majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Immune mediators may affect IBC progression and metastasis installation. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of prognostic biomarkers for IBC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in IBC and Non-IBC patients with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: Fifteen analytes: 5 cytokines (IL-8, IL-16, IL-21, IL-22 and MIF), 7 chemokines (Eotaxin, eotaxin-3, Fractalkine, IP-10, MIP-1α, MIP-1ß and SDF-1α), One growth factors (FGF-2) and 2 soluble receptors (TNFRII and Tweak); were significantly differentially expressed between the two groups. ROC curves showed that twelve of them (IL-8, IL-16, IL-21, IL-22, MIF, MIP-1α, MIP-1ß, SDF-1α, TNFRII, FGF-2, Eotaxin-3, and Fractalkine) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, seven cytokines: IL-8, IL-16, MIF, Eotaxin-3, MIP-1α, MIP-1ß, and CD-30 are positively associated with patients who developed distant metastasis. Ten analytes: Eotaxin-3, Fractalkine, IL-16, IL-1α, IL-22, IL-8, MIF, MIP-1α, MIP-1ß, and TNFRII are positively associated with patients who had Lymph-Nodes invasion. CONCLUSION: This study has uncovered a set of 8 analytes (Eotaxin-3, Fractalkine, IL-16, IL-8, IL-22, MIF, MIP-1α, MIP-1ß) that can be used as biomarkers of IBC, and can be utilized for early detection of IBC, preventing metastasis and lymph-Nodes invasion.

Variant Characterization of a Representative Large Pedigree Suggests "Variant Risk Clusters" Convey Varying Predisposition of Risk to Lynch Syndrome.

Recently, worldwide incidences of young adult aggressive colorectal cancer (CRC) have rapidly increased. Of these incidences diagnosed as familial Lynch syndrome (LS) CRC, outcomes are extremely poor. In this study, we seek novel familial germline variants from a large pedigree Tunisian family with 12 LS-affected individuals to identify putative germline variants associated with varying risk of LS. Whole-genome sequencing analysis was performed to identify known and novel germline variants shared between affected and non-affected pedigree members. SNPs, indels, and structural variants (SVs) were computationally identified, and their oncological influence was predicted using the Genetic Association of Complex Diseases and Disorders, OncoKB, and My Cancer Genome databases. Of 94 germline familial variants identified with predicted functional impact, 37 SNPs/indels were detected in 28 genes, 2 of which (MLH1 and PRH1-TAS2R14) have known association with CRC and 4 others (PPP1R13B, LAMA5, FTO, and NLRP14) have known association with non-CRC cancers. In addition, 48 of 57 identified SVs overlap with 43 genes. Three of these genes (RELN, IRS2, and FOXP1) have a known association with non-CRC digestive cancers and one (RRAS2) has a known association with non-CRC cancer. Our study identified 83 novel, predicted functionally impactful germline variants grouped in three "variant risk clusters" shared in three familiarly associated LS groups (high, intermediate and low risk). This variant characterization study demonstrates that large pedigree investigations provide important evidence supporting the hypothesis that different "variant risk clusters" can convey different mechanisms of risk and oncogenesis of LS-CRC even within the same pedigree.

Immune checkpoints as potential theragnostic biomarkers for epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. EOC is asymptomatic in early stages, so most patients are not diagnosed until late stages, highlighting the need to develop new diagnostic biomarkers. Mediators of the tumoral microenvironment may influence EOC progression and resistance to treatment. AIM: To analyze immune checkpoints to evaluate them as theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 16 immune checkpoints were determined in EOC patients and healthy controls using the MILLIPLEX MAP® Human Immuno-Oncology Checkpoint Protein Magnetic Bead Panel. RESULTS: Seven receptors: BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2 are differentially expressed between EOC and healthy controls. Serum levels of immune checkpoints in EOC patients are positively significantly correlated with levels of their ligands, with a higher significant correlation between CD80 and CTLA4 than between CD28 and CD80. Four receptors, CD40, HVEM, PD-1, and PD-L1, are positively associated with the development of resistance to Taxol-platinum-based chemotherapy. All of them have an acceptable area under the curve (>0.7). CONCLUSION: This study has yielded a first panel of seven immune checkpoints (BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2) associated with a higher risk of EOC and a second panel of four immune checkpoints (CD40, HVEM, PD-1, PD-L1) that may help physicians to identify EOC patients who are at high risk of developing resistance to EOC chemotherapy.

VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer.

Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer. This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC). In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42.3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs. In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090). Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS. Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC. Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.

Identification of two theranostic biomarker panels for epithelial ovarian cancer.

BACKGROUND: Epithelial Ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. Because the disease is asymptomatic in early-stage, the majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Mediators of tumoral microenvironment may affect EOC progression and resistance to treatment. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: Twenty-one analytes: 7 cytokines (IFN-γ, IL-12p70, IL-13, IL-18 and TSLP), 7 chemokines (Eotaxin, eotaxin-2, IP-10, BLC, I-TAC, SDF-1α, and fractalkine), 2 growth factors (MMP-1, VEGF-α), and 5 soluble receptors (APRIL, CD40L, TWEAK, CD30 and TNFRII; were significantly differentially expressed between the two groups. ROC curves showed that only seven of them (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine, and Tweak) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, five cytokines: IFN-γ, IL-1 ß, IL-8, MIP-1ß, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT). CONCLUSION: This study has revealed a first panel of 7 analytes (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine and Tweak) that can be used for early detection of EOC and a second panel of five cytokines (IFN-γ, IL-1ß, IL-8, MIP-1ß, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Effects of multimodal training program on muscle deoxygenation in women with breast cancer: A randomized controlled trial.

Purpose: Chemotherapy and/or radiation are the most often delivered treatments to cancer patients. Usually during the adjuvant treatment, patients complain about fatigue. In addition, physical exercise during adjuvant treatment of cancer seems to have beneficial effects. The aim of this investigation was to assess the effects of multimodal aerobic and strength exercises programs on muscle deoxygenation of patients with breast cancer undergoing adjuvant chemotherapy treatment. Methods: Thirty-two women with breast cancer (20 patients as the training group and 12 patients as the control group) undergoing adjuvant chemotherapy participated in the study. The training group took part in 6 weeks of supervised intermittent aerobic cycling, home-based walking, isometric and electrical muscle stimulation (EMS) exercise training programs. The Outcome measures were muscle deoxygenation (ΔHHb), Maximal Voluntary isometric Contraction (MViC) and Endurance Time (ET) before and after the training period. Results: Compared to the control group, a significant increase in ΔHHb (P < 0.01) accompanied with an increase in ET (P < 0.01) and MViC (P < 0.01) of the quadriceps was obtained in the training group. However, no significant differences of MViC, ET and ΔHHb were observed in the control group. Conclusion: Multimodal aerobic and strength exercise programs enhance muscle oxygen utilization, which may partly explain the improvement in muscular strength and endurance, and the reduction of muscle fatigue in patients with breast cancer during an adjuvant chemotherapy period.

Clinical and pathological characteristics, treatment outcome and prognostic factors in adult rhabdomyosarcoma: a monocentric retrospective study.

Rhabdomyosarcoma (RMS) is rare in adults. Our study is the first in Tunisia to report outcomes of adult RMS. We retrospectively analyzed clinical data of adult RMS patients. We collected data regarding clinical characteristics, treatment outcome and prognostic factors. Survival was assessed using the Kaplan Meier method. Forty-seven patients were included. Median age was 39. Twenty-five patients were young adults (53%). Sex ratio (M/F) was 1.9. RMS was localized in 33 patients (70%) and metastatic in 14 patients (30%). Extremities were the most frequent tumor site (40%) followed by trunk (23%). Median tumor size was 9 cm. Pleomorphic RMS was the major subtype (36%). Twenty seven of 33 patients with localized RMS underwent surgery (82%). Relapse free survival (RFS) was 38%. Young adults had a significantly worse RFS than adults aged ≥40 (p = 0.045). Surgery was associated with a significantly better RFS (p = 0.023). Five year overall survival (OS) was 35% and 27% in localized and metastatic RMS respectively. RMS localized in the extremities had significantly poorer OS (p = 0.041), same as non-operated patients (p = 0.025). OS for metastatic RMS was significantly worse after surgery of the primary tumor (p = 0.002). In multivariate analysis, surgery (HR = 0.108; 95%CI (0.023-0.519); p = 0.005) and non-extremity localization (HR = 0.238; 95%CI (0.075-0.751); p = 0.014) were independent prognostic factors for OS in localized RMS. Adults with RMS have poor 5 year OS. Surgery and non-extremity localization were independent prognostic factors for OS in localized RMS.

Evaluation of cfDNA as an early detection assay for dense tissue breast cancer.

A cell-free DNA (cfDNA) assay would be a promising approach to early cancer diagnosis, especially for patients with dense tissues. Consistent cfDNA signatures have been observed for many carcinogens. Recently, investigations of cfDNA as a reliable early detection bioassay have presented a powerful opportunity for detecting dense tissue screening complications early. We performed a prospective study to evaluate the potential of characterizing cfDNA as a central element in the early detection of dense tissue breast cancer (BC). Plasma samples were collected from 32 consenting subjects with dense tissue and positive mammograms, 20 with positive biopsies and 12 with negative biopsies. After screening and before biopsy, cfDNA was extracted, and whole-genome next-generation sequencing (NGS) was performed on all samples. Copy number alteration (CNA) and single nucleotide polymorphism (SNP)/insertion/deletion (Indel) analyses were performed to characterize cfDNA. In the positive-positive subjects (cases), a total of 5 CNAs overlapped with 5 previously reported BC-related oncogenes (KSR2, MAP2K4, MSI2, CANT1 and MSI2). In addition, 1 SNP was detected in KMT2C, a BC oncogene, and 9 others were detected in or near 10 genes (SERAC1, DAGLB, MACF1, NVL, FBXW4, FANK1, KCTD4, CAVIN1; ATP6V0A1 and ZBTB20-AS1) previously associated with non-BC cancers. For the positive-negative subjects (screening), 3 CNAs were detected in BC genes (ACVR2A, CUL3 and PIK3R1), and 5 SNPs were identified in 6 non-BC cancer genes (SNIP1, TBC1D10B, PANK1, PRKCA and RUNX2; SUPT3H). This study presents evidence of the potential of using cfDNA somatic variants as dense tissue BC biomarkers from a noninvasive liquid bioassay for early cancer detection.

Clinico-Epidemiological Profile, Prognostic Factors and Treatment Outcome of Refractory Hodgkin Lymphoma.

Approximately 5-10% of patients with Hodgkin lymphoma are refractory to initial treatment. The aim of our study was to assess the clinico-epidemiological profile, prognostic factors and treatment outcome. A retrospective study was conducted over a period of 12 years between June 2006 and January 2018 at the oncology department of Salah Azaïz Institute. Thirty-one patients were included. The median age was 27 years with a female predominance (sex ratio = 0.93).The majority had an advanced stage (61%). IGEV regimen was the most commonly used salvage chemotherapy (n = 14). Age above 30 years was predictive of treatment failure after salvage therapy (p = 0.003). IGEV regimen showed better results than ICE protocol in terms of response to salvage therapy (p = 0.048). Seven patients had salvage radiotherapy. Four patients had autologous stem cell transplant. Progressive disease (n = 12) was the main cause of non-eligibility of autologous stem cell tansplant. Overall survival and progression free survival at 3 years were 50% and 5% respectively. The prognostic factors influencing the overall survival were age above 30 years (p = 0.001), advanced Ann Arbor stage before progression (p = 0.02), advanced Ann Arbor stage of refractory Hodgkin lymphoma (p = 0.001), histological subtype (p = 0.001), CD20 expression (p = 0.027) and non-response to salvage therapy (p = 0.004). The prognostic factor influencing progression free survival was the non-response to salvage therapy (p = 0.045). The prognosis of refractory Hodgkin lymphoma remains poor. The current standard secondary treatment consists of combination therapy, usually followed by autologous stem cell transplantat. Innovative therapies are needed to improve the prognosis of refractory Hodgkin lymphoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01463-4.

Decreased risk of ovarian cancer associated with rs9898876 sex hormone-binding globulin gene variant.

BACKGROUND: Ovarian cancer (OC) is one of the most common gynecologic cancers,with significant morbidity and mortality. The risk of OC is influenced by hormone status, of which sex hormone-binding globulin (SHBG), which influences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC. The aim of this study is to evaluate the involvement of common SHBG gene variants in OC susceptibility and evolution. MATERIALS: A case control study including 71 OC patients and 74 cancer-free controls, who were genotyped for rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP. Genotyping was done by the allelic discrimination method, using VIC- and FAM-labeled primers. RESULTS: The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no significant associations of the tested variants and overall OC risk. Taking homozygous wild-type genotype as reference (OR = 1.00), heterozygous rs9898876 (G/T), and minor allele-carrying genotypes [G/T + T/T] were associated with reduced risk of OC. While rs9898876 heterozygosity (G/T) was predictive of OC occurrence, no significant association of the remaining three tested SNPs was noted with altered risk of OC. Irrespective of FIGO staging, the four tested SHBG SNPs were not associated with the clinical progression of OC. CONCLUSIONS: In conclusion, SHBG rs9898876 is associated with a decreased risk of OC, and thus constitutes a potential diagnostic biomarker of OC.

An Open-Label, Multinational, Multicenter, Phase IIIb Study with Subcutaneous Administration of Trastuzumab in Patients with HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction.

OBJECTIVE: This study was designed to investigate treatment satisfaction in patients and Health Care Professionals (HCP) and to evaluate the safety and tolerability of subcutaneous (SC) trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC). MATERIALS AND METHODS: Two-hundred and twenty-three patients with eBC were screened, of whom 173 patients met the eligibility criteria and received at least one dose of SC trastuzumab. The primary efficacy endpoint was to assess patient satisfaction via a questionnaire. RESULTS: The majority of patients (n = 166, 97.6%) reported satisfaction with the SC route. Patients and HCPs stated that SC trastuzumab was easy to use (93.5% and 62.5%, respectively) compared to the intravenous (IV) route and all HCPs (n = 16) expressed satisfaction with the SC route. Progression, disease recurrence or death was reported in 24 patients (13.8%) by two years of follow up. Four-year disease-free survival (DFS) and overall survival (OS) rates were 84.2% (±3.1) and 90.5% (±4.7), respectively. A total of 1299 adverse events (AEs) were recorded over 4-years follow-up, nearly 97% of which were judged non-serious. The most common AEs were arthralgia (n = 54, 4.2%), flu-like symptoms (n = 41, 3.2%) and nausea (n = 39, 3.0%). Fifty-four cardiac events, including left ventricular dysfunction, left ventricular failure and cardiotoxicity, were reported. Ejection fraction (EF) decrease [median decrease 3.5% (0.12-19.0)] was reported in 5.4% of cases. SC trastuzumab treatment was interrupted due to decreased EF in two cases. CONCLUSION: SC trastuzumab was widely acceptable to both patients and HCPs. The safety and tolerability of SC trastuzumab was consistent with the known safety profile of SC and IV administration.

Skin toxicity after Filgrastim treatment for an Ewing's sarcoma patient.

INTRODUCTION: Filgrastim is a granulocyte colony-stimulating factor (GSCF) used in some chemotherapy regimen to prevent febrile neutropenia. Most common reaction of filgrastim are aches and pain including headaches, nausea and skin rash. CASE REPORT: We report the case of a patient who developed unusual, non-commonly reported adverse toxidermy to filgrastim. At first the eruption was limited to the lower members and genetics organs. Then it slowly spread across the whole body presenting as a polymorphic exanthematous-pustulosis lesions. MANAGEMENT & OUTCOME: A cutaneous biopsy was done, identifying a toxidermy modified by systemic treatment. A pharmacological study linked the role of filgrastim to these lesions. After switching from filgrastim to lénograstim, his lesions are completely gone and haven't flared up again. Thus, clearly imputing the use of filgrastim. DISCUSSION: The cutaneous reaction that has reported with use of GSCF are sweet syndrome, erythema nodosum, pyoderma nodosum and pyoderma gangrenosum. As far as we know, no acute generalized exanthematous pustulosis due to GSCF has been reported.

Association of HLA-G 3'UTR polymorphisms and haplotypes with colorectal cancer susceptibility and prognosis.

Human leukocyte antigen (HLA)-G has been considered as an immune modulator in several types of cancers. Its genetic polymorphisms may potentially affect the risk of developing colorectal cancer (CRC). The overall purpose of this study was to analyze the implication of HLA-G 3'untranslated region (3'UTR) polymorphisms particularly 14 pb insertion/deletion (Ins/Del; rs371194629) and + 3142C/G (rs1063320) in CRC susceptibility and progression. A comparative analysis between patients (N = 233) and controls (N = 241) demonstrated that Del allele (Odds Ratios (OR) = 1.41, 95% CI = 1.091-1.819, p = 0.008), the homozygous Del/Del genotype (OR = 1.80, 95% CI = 1.205-2.664, p = 0.003) and the codominant C/G genotype (OR = 1.59, 95% CI = 1.106-2.272, p = 0.013) were associated to CRC risk. As expected, the DelG haplotype was associated with CRC susceptibility (OR = 1.47, 95% CI = 1.068-2.012, p = 0.018). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele and the homozygous Del/Del genotype were associated with reduced event free survival (EFS) (Respectively, p = 0.009 and p = 0.05). Interestingly, the Del allele and the homozygous Del/Del genotype have been revealed as independent prognostic factors for poor EFS in patients with CRC. Additionally, haplotypes analysis revealed that DelG haplotype was linked with significant increase in CRC risk (log-rank; EFS: p = 0.02). Inversely, the InsC haplotype was associated with a significant reduced CRC risk (log-rank; Overall survival (OS): p < 10-6; EFS: p = 0.01). Multivariate Cox regression analysis revealed that the InsC haplotype was independently associated with significantly longer EFS (p = 0.021, HR = 0.636, 95% CI = 0.433-0.935). These findings support the implication of HLA-G polymorphisms in the CRC susceptibility suggesting HLA-G as a potent prognostic and predictive indicator for CRC. Insight into mechanisms underlying HLA-G polymorphisms could allow for the development of targeted care for CRC patients according to their genetic profile.

COVID-19 Vaccination Acceptance and Its Associated Factors among Cancer Patients in Tunisia.

BACKGROUND: Vaccination is the most effective way to fight the COVID-19 pandemic and to protect people who have a higher risk of developing severe illness and death from COVID-19 such as cancer patients. We aimed in this study to determine the acceptance rate of COVID-19 vaccination of the Salah Azaiez Institute (SAI) of cancer of Tunisia patients and to identify its associated factors. METHODS: It was a cross sectional study about patients admitted to the SAI for treatment during the month of February 2021. Univariate and multivariate analyses were performed to identify factors associated with the COVID-19 vaccine acceptance among Tunisian cancer patients. RESULTS: A total of 200 patients were included in this study with a mean age of 54.4±12.7 years and a gender ratio of 0.5. Only 35.0% of surveyed patients reported their acceptance to receive the COVID-19 vaccine. Multivariate analysis showed that believing in COVID-19 vaccine safety and efficacy (OR=3.1 [1.3-7.4]), enrollment in the COVID-19 vaccine platform (OR=8.3 [1.8-38.1]) and the willingness to receive influenza vaccine (OR=3.9 [1.6-9.3]) were independently associated with the COVID-19 vaccine acceptance among SAI cancer patients. CONCLUSIONS: The COVID-19 vaccine acceptance rate found in this study was low. Communication strategies of the vaccination campaigns should provide clear, simple and detailed messages about the efficacy and the benefits of the COVID-19 vaccines. More engagement of health authorities to promote COVID-19 vaccination is necessary.

Prognostic significance of high circulating sHLA-G in ovarian carcinoma.

HLA-G is a non-classical major histocompatibility complex class Ib molecule. Its expression has been described in various cancer types, including ovarian cancer. HLA-G molecule has been implicated in immune escape and in progression of ovarian tumor cells. Our goal was to assess if total soluble (s)HLA-G molecules or HLA-G5 and sHLA-G1 isoforms could be considered as circulating ovarian tumor biomarkers, we measured the concentration of these molecules in ovarian carcinoma patients stratified according with their clinicopathological parameters. sHLA-G, sHLA-G1 and HLA-G5 concentrations were dosed in plasma samples by sandwich-ELISA. The sHLA-G dimerization was analyzed after immunoprecipitation and SDS-PAGE migration. Total sHLA-G and sHLA-G1 levels were significantly represented in plasma of ovarian carcinoma patients compared to healthy controls. sHLA-G1 isoform concentration was highly represented in ovarian carcinoma compared to HLA-G5 isoforms. Additionally, high sHLA-G molecules have been found in aged patients, as well as in patients with advanced stages, and those with metastatic lymph nodes and those with distant metastasis. Elsewhere, sHLA-G monomers were highly represented in ovarian carcinoma patients compared to controls. sHLA-G plasmatic protein was highly represented in ovarian carcinoma. In effect, HLA-G might be considered as a new checkpoint molecule that could be used to assess progression and recurrence of the disease, thus placing it as a potential biomarker for advanced and complicated ovarian carcinoma.

An Acute Jejunojejunal Intussusception Revealing a Metastatic Combined Lung Cancer.

Intussusception is a relatively common disease in pediatric age but it is uncommon in adults. We report a case of a 49-year-old male who presented with an acute jejunojejunal intussusception revealed by abdominal pain and vomiting. He underwent an en bloc resection, and pathological findings concluded to a metastasis of a pulmonary combined small cell carcinoma and adenocarcinoma. A subsequent CT scan revealed the primitive mass of the right lung with no evidence of secondary localization. The biopsy was difficult to perform. The patient underwent a pneumonectomy with lymph node dissection confirming the same diagnosis. He made a good recovery from the surgery, and a postoperative chemotherapy was administrated, and he is in remission until this date.

Fecal Metabolic Profiling of Breast Cancer Patients during Neoadjuvant Chemotherapy Reveals Potential Biomarkers.

Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients (n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.