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PURPOSE: The purpose of this study was to evaluate acute skin toxicity in early breast cancer patients treated with hypofractionated radiotherapy (HFRT) after breast-conserving surgery and to identify factors predictive for grade ≥â¯2 acute skin toxicity. MATERIALS AND METHODS: A monocentric retrospective study was carried out using cases treated between December 2017 and November 2020. We analyzed data from 202 patients with early breast cancer treated with 3D hypofractionated RT (40.05â¯Gy in 15 fractions) to the whole breast with or without regional lymph nodes, followed by 13.35â¯Gy in 5 fractions to the tumor bed. Acute skin toxicity was monitored during RT according to CTCAE (common toxicity criteria for adverse events) scale. Univariate and multivariate analyses were performed to assess predictive factors of acute skin toxicity. RESULTS: Overall, there was no erythema in 9%, grade 1 erythema in 64.5%, grade 2 in 24%, and grade 3 in 2.5%. No grade 4 erythema was seen. Median delay between RT initiating and maximum skin reaction was 22 days (range 4-44 days). No patient interrupted treatment. In univariate analysis, the rate of acute skin toxicity grade 2---3 (G2-3) was significantly higher for patients with larger tumor size (pâ¯= 0.02), body mass index >â¯27 (pâ¯= 0.04), and time between chemotherapy (CT) and RT less than 20 days (pâ¯= 0.01). Dosimetric risk factors for acute skin toxicity G23 were breast volume >â¯800â¯cc (pâ¯= 0.000), boost volume >â¯18â¯cc (pâ¯= 0.002), V105% >â¯40â¯cc (pâ¯= 0.03), and Dmax >â¯56â¯Gy (pâ¯= 0.007). CT, trastuzumab, regional lymph node radiation, and age were not correlated with increased skin toxicity. In multivariate analysis, acute skin toxicity correlated with T stage (pâ¯= 0.032), breast volume >â¯800â¯cc (pâ¯= 0.012), boost volume >â¯18â¯cc (pâ¯= 0.04), and Dmax >â¯56â¯Gy (pâ¯= 0.035). CONCLUSION: Our results confirm that whole breast with or without lymph nodes hypofractionated RT is safe and well tolerated. The factors strongly associated with a decreased risk of G23 skin toxicity are T1, breast volume <â¯800â¯c, boost volume <â¯18â¯cc, and Dmax <â¯56â¯Gy. Long-term follow-up is needed to evaluate late toxicity.
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Neoplasias da Mama , Mastectomia Segmentar , Humanos , Feminino , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mama/patologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodosRESUMO
PURPOSE: The aim of the present study was to measure the frequency and types of IPV among patients with cancer and evaluate risk factors. METHODS: The study was a cross-sectional, questionnaire-based study, conducted between January and April 2022, including 141 patients treated with cancer regardless of gender, site, or stage. We developed the study questionnaire by adapting items from the "WHO multi-country questionnaire on violence against women" and "The Women's Experiences with Battering Scale." Odds ratio (OR) and spearman tests were performed to assess the impact of several factors associated with the reported IPV. RESULTS: Median age was 50 years old, 38.3% were male cancer patients. IPV prevalence was 24.8%, we observed 5 cases of torture (3%). The most common forms of violence were placing severe restriction on certain types of food and clothing in 21%, psychological violence in 20%, exposing intimate information about the patient health status to others in 17%, ignoration in 13.5%, putting restrictions on visiting friends or families in 9.2%, verbal assault in 9.2%, physical violence in 7.9%, and 7.1% racist conducts. Financial violence was rare in 4.3%. There was no difference in the incidence of IPV between man and women. We observed a significant correlation between IPV prevalence and disease stage (19.1% M0 vs 34.6% M1, p=0.04, OR=2.2 [1-4.8]), patient's educational level (48.5% vs 17.6%, p=0.01, OR= 4.4 [1.8-10.2]), and being under ongoing cancer therapy (11.4% vs 30.9%, p=0.013, OR=3.4 [1.2-9.7]) CONCLUSION: Patients were shown to be victims of several forms of IPV regardless of gender.
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Violência por Parceiro Íntimo , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Violência por Parceiro Íntimo/psicologia , Fatores de Risco , Inquéritos e Questionários , Parceiros Sexuais/psicologia , Neoplasias/epidemiologia , PrevalênciaRESUMO
INTRODUCTION: We aimed to measure the acceptability towards the COVID-19 vaccination in cancer patients and to investigate determinant factors associated with the patient's choice. METHODS: We conducted a cross-sectional survey with a self-administered questionnaire delivered to 329 cancer patients in 3 oncology cancer centers in Tunisia between February-May 2021. Logistic regression was used to evaluate odds ratio predicting patient's intentions toward the vaccine. RESULTS: Acceptance rate was 50.5%, 28.3% (n = 93) reported to definitely refuse the vaccine and 21.2% (n = 70) did not make their decision yet. High educational level, history of comorbidities, history of influenza vaccination in the current season, and patient's opinion about the severity of COVID-19 did not predict vaccine resistance. However, patients who think that the vaccine may interfere with treatment efficacy (OR = 7.28, 95%CI [2.5-12.32]), or may impact cancer outcome (OR = 6.14, 95%CI [2.27-16.7]), were significantly more likely to refuse the vaccine. Patients who disagree that the vaccine is a major weapon against the pandemic (OR = 6.07, 95%CI [2.34-9.52]) or that it could reduce the virus transmission (OR = 7.34, 95%CI [4.22-11.81]) were also significantly more likely to reject the vaccination. Safety concerns were also significant predictive factors (OR = 7.9, 95%CI [4.10-11.27]. Confidence level in the authorities played a significant role in patient's acceptance of the vaccine, indeed patients who are not registered (OR = 5.9, 95%CI [1.58-8.7]) or not informed about the Tunisian national vaccination platform EVAX (OR = 5.51, 95%CI [2.1-7.9]) were more likely to be against the vaccine. CONCLUSION: Cancer patient's education about the impact of the vaccine on their disease and on the COVID-19 is needed. Governments should build strategies to gain more population confidence.
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COVID-19 , Vacinas contra Influenza , Neoplasias , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Neoplasias/terapia , SARS-CoV-2 , VacinaçãoRESUMO
INTRODUCTION: Drug-induced acute pancreatitis (AP) is uncommon and represents 0.1 to 2% of all AP cases. Chemotherapy-induced AP is very rare. Docetaxel monotherapy-induced AP has been reported only once in the literature. Herein we report the second case of docetaxel-related AP and the first case of necrotic AP induced by this agent. CASE REPORT: We describe the case of a severe docetaxel-induced AP classified as stage E Balthazar in a 55-year-old female treated with adjuvant docetaxel for localized breast cancer. Symptoms occurred five hours following the first infusion of docetaxel. MANAGEMENT AND OUTCOME: The patient was hospitalized for 15 days for appropriate management. According to the CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 this was a grade 4 toxicity and chemotherapy was withdrawn thereafter. Drug rechallenge was not possible because of the severity of the presentation. DISCUSSION: Medical oncologists should be aware that docetaxel may induce severe pancreatitis. Therefore, they should prompt testing of serum lipase when patients consult for unusual abdominal pain following chemotherapy infusion. Recognizing this entity is paramount to allow early and appropriate management.
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Neoplasias da Mama , Pancreatite , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Docetaxel/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Pancreatite/induzido quimicamente , Pancreatite/diagnósticoRESUMO
BACKGROUND: Cancer care-related out-of-pocket expenses and financial toxicity (FT) are a rising burden for patients. We aimed to evaluate patient-reported FT and to identify relevant correlates within a Tunisian population. METHODS: We conducted a survey using the 11-item Comprehensive Score for Financial Toxicity (COST) that could range from 0 = high to 44 = low. FT was grade 0 if ≥ 26, grade 1 = (14-25), grade 2 = (1-13), and grade 3 = 0. Scores were collected along with data regarding patient medical/social features and out-of-pocket expenses. Univariate and multivariate analyses were performed to identify factors associated with higher financial burden. RESULTS: Among the 179 participants, median COST score was 20.8 (Q1 17-Q3 24), with 80.4% of patients experiencing financial toxicity: grade 0 = 20%, grade 1 = 68.4%, grade 2 = 11.7%, grade 3 = 0%. Most patients (66.5%) used to work before cancer and 44.7% reported ceasing work because of cancer. The time to go to the hospital was > 30 min in 66.5% of cases. Unemployment, time to hospital > 30 min, ceasing work because of cancer, and expenses on non-chemotherapy drugs exceeding 70 dinars (25 US dollars) were mostly associated with higher FT on univariate analysis. Distance to hospital and ceasing work because of cancer were the single most significant factors in multivariate analysis. CONCLUSIONS: Losing work due to cancer and unequal distribution of health care particularly in cities with long travel times to the nearest hospital are the main sources of financial distress.
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Efeitos Psicossociais da Doença , Estresse Financeiro/psicologia , Gastos em Saúde/estatística & dados numéricos , Neoplasias/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes/psicologia , Inquéritos e Questionários , Tunísia , Desemprego/psicologia , Adulto JovemRESUMO
BACKGROUND: A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. METHODS: A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein-protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. RESULTS: Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein-protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. CONCLUSIONS: In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific.
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Neoplasias da Mama/genética , Sequenciamento do Exoma , Predisposição Genética para Doença , Alelos , Neoplasias da Mama/epidemiologia , Família , Feminino , Genes Neoplásicos , Estudos de Associação Genética , Variação Genética , Humanos , Masculino , Linhagem , Mapas de Interação de Proteínas , TunísiaRESUMO
Purpose: This study aimed to explore the experiences of young adult cancer patients within the Tunisian context. Methods: A total of 104 patients between the ages of 20 and 40, undergoing treatment for various types and stages of cancer, participated in a questionnaire-based survey. The survey encompassed topics related to the socioeconomic and psychological impacts of cancer, coping mechanisms, relationships, sexuality, and future aspirations. Results: Of the participants, 78 were women (75%) and 26 were men (25%), with an average age of 33 years. Financial difficulties were reported by 60 patients (57.7%). The most common emotional responses to the diagnosis were sadness (54.8%), followed by denial (18.3%) and anger (5.8%). Thirteen patients (12.5%) choose not to receive information about the stage of their disease. In addition, 42 patients (40.4%) experienced a decrease in perceived physical attractiveness, while negative effects on sexuality were observed in 44.2% of cases. The primary concerns reported by patients were the fear of recurrence or progression (48%) and infertility (48%). Furthermore, 43 patients (41.3%) expressed a decrease in self-confidence, notably influenced by financial difficulties (OR: 2.77 [95% CI: 1.12-6.87]), physical alterations (OR: 0.18 [95% CI: 0.07-0.45]), and sexual issues (OR: 0.17 [95% CI: 0.06-0.48]). Notably, 78 patients (75%) continued to make future plans, particularly those under 30 years of age (OR: 0.2 [95% CI: 0.04-0.96]). Moreover, 47.1% of patients expressed an inclination toward immigration to developed countries, primarily due to perceived superior health care systems (61.5%). Conclusions: Young cancer patients face a range of social and psychological challenges, suggesting the necessity for a specialized care approach.
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Neoplasias , Humanos , Masculino , Feminino , Adulto , Neoplasias/psicologia , Tunísia , Adulto Jovem , Inquéritos e Questionários , Adaptação PsicológicaRESUMO
Since the early description more than a century ago, inflammatory breast cancer (IBC) remains an aggressive disease, with a different geographic repartition, with the highest ones incidence reported in the North of Africa (Tunisia, Algeria, Morocco, and Egypt), and the lowest incidence in Western countries (USA, Europe ). In this study, we reviewed the literature using the Surveillance, Epidemiology, and End Results (SEER) database compared to other published series. We observed that in the high incidence areas (North of Africa) when compared to "classical" breast cancer, IBC was associated to younger age (less than 50 years) with rapid evolution of signs and symptoms (in less than 3 up to 6 months), and more aggressive clinical and histopathological-molecular parameters, due to the predominance of triple-negative and HER2+ subtypes in around 60% of cases. An epidemiologic trend was observed in both high and low incidence areas since the eighties are towards reduction of IBC prevalence. Concerning Tunisia, in comparison with the historical series of the 1980s, the incidence decreased in part by applying more stringent diagnostic criteria but also probably due to a slight improvement of the socio-economic level (SEL). This trend was also observed in the US, due to the efforts of collaborative IBC groups from MD Anderson Cancer Center (MDACC), Duke and IBC patient advocacy groups. Therapeutic results are slightly better due to the standardization of a multidisciplinary approach and the use of combined primary chemotherapy and/or targeted therapies (especially in HER2 positive patients), followed by mastectomy plus radiotherapy. The 5-year overall and disease-free survival is at more than 60%, related to an IBC mortality decrease observed in the cohorts of patients treated in the last decade.
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Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias Inflamatórias Mamárias/terapia , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Mastectomia , TunísiaRESUMO
Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries.
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INTRODUCTION: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.
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Precision Medicine is being increasingly used in the developed world to improve health care. While several Precision Medicine (PM) initiatives have been launched worldwide, their implementations have proven to be more challenging particularly in low- and middle-income countries. To address this issue, the "Personalized Medicine in North Africa" initiative (PerMediNA) was launched in three North African countries namely Tunisia, Algeria and Morocco. PerMediNA is coordinated by Institut Pasteur de Tunis together with the French Ministry for Europe and Foreign Affairs, with the support of Institut Pasteur in France. The project is carried out along with Institut Pasteur d'Algérie and Institut Pasteur du Maroc in collaboration with national and international leading institutions in the field of PM including Institut Gustave Roussy in Paris. PerMediNA aims to assess the readiness level of PM implementation in North Africa, to strengthen PM infrastructure, to provide workforce training, to generate genomic data on North African populations, to implement cost effective, affordable and sustainable genetic testing for cancer patients and to inform policy makers on how to translate research knowledge into health products and services. Gender equity and involvement of young scientists in this implementation process are other key goals of the PerMediNA project. In this paper, we are describing PerMediNA as the first PM implementation initiative in North Africa. Such initiatives contribute significantly in shortening existing health disparities and inequities between developed and developing countries and accelerate access to innovative treatments for global health.
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Through this case presentation and a review of the literature, we aim to describe clinical and pathologic features and to distinguish the outcome of these tumors. A 25-year-old woman presented with pelvic pain and an iliac mass. Workup revealed a 53-mm cystic partitioned mass of the left ovary infiltrating the left sacrum. She underwent a left adnexectomy. Gross examination revealed a ruptured ovarian mass. When dissected, it showed grayish cerebroid aspects. Histologic examination revealed a malignant tumor proliferation of the diffuse large cells. An immunohistochemical analysis showed negative results for PLAP, αFP, ßHCG, CD117, CK20, and CD30. It also showed lack of B markers and T marker (CD3) and an expression of CD138 and anaplastic lymphoma kinase. The patient was treated by 6 cycles of CHOP chemotherapy and a pelvic radiotherapy. She presented with a 15-cm splenomegaly 26 months later and died of febrile neutropenia. Most patients follow an aggressive disease and are unlikely to respond to the standard.
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Biomarcadores Tumorais/metabolismo , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Receptores Proteína Tirosina Quinases/metabolismo , Adulto , Quinase do Linfoma Anaplásico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Diferenciação Celular , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Prednisona/administração & dosagem , Vincristina/administração & dosagemRESUMO
OBJECTIVE: Previous data hypothesise that women receiving aromatase inhibitors (AIs) exhibit worse cognitive functioning than patients on tamoxifen (TAM) since their oestrogen levels are lower. We aimed to compare cognitive complaints in both groups. METHODS: From September 2020 to January 2021, we conducted a cross-sectional study on patients with stage I-III breast cancer undergoing adjuvant endocrine therapy for at least 6 months. Cognitive complaints were assessed using the Functional Assessment of Cancer Therapy-Cognitive V.3 questionnaire with higher scores indicating better outcomes. RESULTS: We included 108 female patients, 60 on AI and 48 on TAM. Mean age at diagnosis was 52 (44 in the TAM group vs 58 in the AI group, p<0.001). Assessment of 'perceived cognitive impairment-20 subscale' did not identify a significant difference between the two groups (mean score: patients on AI=63/80 vs patients on TAM=58/80, p=0.198). Patients on TAM scored significantly worse than patients on AI (p<0.001) on the concentration complaints, while for the verbal domain, memory, multitasking, speed and functional interference, no significant difference between the two groups was observed. The difference in concentration complaints was maintained after adjustment to age, educational level, physical activity, prior exposure to chemotherapy, and living alone or with others. Finally, a favourable impact of regular physical activity on concentration scores was observed in both groups (p<0.001). CONCLUSION: Despite age difference, patients on AI did not demonstrate worse complaints than patients on TAM. Patients on TAM exhibited significantly increased concentration complaints. Oncologists should carefully screen their patients for mental fog and educate them on the importance of regular exercise.
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Background and Purpose: We aimed to translate the Comprehensive Score of Financial Toxicity (COST) questionnaire into Arabic and to evaluate its reliability and validity. Methods: We applied the four-step translation method and conducted a pilot validation study over 179 medical oncology patients. Reliability was tested using the Cronbach alpha coefficient and test-retest stability. Validity was tested using the correlation with Functional assessment of Cancer Therapy-General score (FACT-G), factorial analysis and the content validity index. Results: Questionnaire showed high internal consistency and test retest reliability; Cronbach alpha coefficient was 0.77 and Pearson stability coefficient was 0.8. Convergent validity evaluation showed a statistically significant moderate correlation with the FACT-G (r = .42, p =.047). Content validly index was 0.93. Conclusions: The Arabic version of COST questionnaire, was a valid and reliable tool that could be used in clinical practice by healthcare providers to evaluate financial toxicity in Arab speaking cancer patients.
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Estresse Financeiro , Neoplasias , Humanos , Reprodutibilidade dos Testes , Idioma , Traduções , Inquéritos e Questionários , Psicometria/métodosRESUMO
INTRODUCTION: Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. METHODS: We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. RESULTS: Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection (p = 0.009), and a CD8/CD4 ratio (p = 0.008) were prognostic factors for overall survival. Complete surgical resection (p = 0.003), the forkhead box protein P3/CD8 (p = 0.005), and forkhead box protein P3/CD4 (p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate (p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype (p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age (p = 0.004) and a CD8/CD4 ratio (p = 0.016) were independent predictors of overall survival. CONCLUSION: Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma , Neoplasias Pulmonares , Linfócitos T CD8-Positivos/química , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fatores de Transcrição Forkhead/análise , Fatores de Transcrição Forkhead/metabolismo , Humanos , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Microambiente TumoralRESUMO
Breast cancer has different epidemio-clinical characteristics in Middle East and North-African populations compared to those reported in the Western countries. The aim of this study is to analyze the epidemiological and clinico-pathological features of breast cancer in Tunisia and to determine prognostic factors with special interest to family history, Ki-67 proliferation index and comorbidity. We retrospectively reviewed epidemiological and clinico-pathological data from patients' medical records, treated in the Medical Oncology Department at Abderrahmane Mami Hospital, in the period 2011-2015. Data has been collected on 602 breast cancer patients and analyzed using SPSS software V.23.0. Our study showed high fractions of young breast cancer patients and cases with dense breasts. The most prevalent comorbidities observed in the studied cohort were cardiovascular diseases and diabetes. Familial breast cancer was found in 23.3% of cases and was associated with younger age at diagnosis (p<0.001) and advanced stage (p = 0.015). Ki-67 index >20% was significantly associated with early age at diagnosis, lymph node involvement (p = 0.002), advanced tumor grade (p<0.001) and high risk of relapse (p = 0.007). Ki-67 cut-off 30% predicted survival in luminal cases. Survival was worse in patients with triple negative breast cancer compared to non-triple negative breast cancer, inflammatory breast cancer compared to non-inflammatory breast cancer, moderately to poorly differentiated tumors compared to well-differentiated tumors and with positive lymph nodes compared to pN0 (p<0.05). Our study showed new insights into epidemiological and clinico-pathological characteristics of breast cancer that are not well explored in Tunisian population. Considering our findings along with the implementation of electronic health record system may improve patient health care quality and disease management.
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Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67 , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Choriocarcinoma is a rare malignancy originating from trophoblastic cells that is known to arise from the placenta. In this report, we describe the case of a 28-year-old female who consulted for amenorrhea and elevated ßhCG mimicking a pregnancy of an unknown location, which ultimately turned out to be primary choriocarcinoma of the lung.
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BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.
RESUMO
Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.