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Background and Aims: The treatment of metastatic non-small-cell lung cancer (NSCLC) has been revolutionized by the arrival of immune checkpoint inhibitors (ICI). For patients without immune related adverse events (irAEs), it is recommended to continue the treatment as long as it provides clinical benefit or until unacceptable toxicity appears. The aim of our study was to evaluate survival data among patients with advanced or metastatic NSCLC following ICI discontinuation for reasons of long-term response or toxicity (irAEs). Methods: We included all patients with advanced or metastatic NSCLC treated with nivolumab and pembrolizumab at the Centre Jean Perrin, Clermont-Ferrand, France (January 1, 2016 to May 31, 2019). We focused on two groups in this study population: "Voluntary treatment discontinuation" (medical decision as a result of long-term response and patient decision) and "Treatment discontinuation due to toxicity" (irAEs). The primary endpoint was to evaluate the postdiscontinuation outcomes of these two groups: progression-free survival (PFS) and overall survival (OS), and rechallenge in the "voluntary discontinuation" group. Results: The final analysis concerned 146 patients, including 10 (7%) in the "discontinuation due to toxicity" group, 11 (8%) in the "voluntary discontinuation" group, 100 (68%) who discontinued treatment as a result of progression and 25 (17%) whose treatment was still on-going. The median PFS in the "discontinuation due to toxicity" group was not reached, and in the "voluntary discontinuation" group (n = 11) was 37 months (p = 0.4), versus 2 months in the progression group (p < 0.001). The median OS in "discontinuation due to toxicity," and in the "voluntary discontinuation" groups was not reached (p = 0.5), versus 10 months in the progression group (p < 0.001). Conclusion: Treatment discontinuation following long-term response to ICI treatment showed sustained response and long-term survival after discontinuation. The incidence of irAEs was associated with better long-term survival, even after ICI discontinuation.
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Background: Presently, there are few published reports on postoperative radiation therapy for oropharyngeal and oral cavity cancers treated with IMRT/VMAT technique. This study aimed to assess the oncological outcomes of this population treated with postoperative VMAT in our institution, with a focus on loco-regional patterns of failure. Material and methods: Between 2011 and 2019, 167 patients were included (40% of oropharyngeal cancers, and 60% of oral cavity cancers). The median age was 60 years. There was 64.2% of stage IV cancers. All patients had both T and N surgery. 34% had a R1 margin, 42% had perineural invasion. 72% had a positive neck dissection and 42% extranodal extension (ENE). All patients were treated with VMAT with simultaneous integrated boost with three dose levels: 66Gy in case of R1 margin and/or ENE, 59.4-60Gy on the tumor bed, and 54Gy on the prophylactic areas. Concomittant cisplatin was administrated concomitantly when feasible in case of R1 and/or ENE. Results: The 1- and 2-year loco-regional control rates were 88.6% and 85.6% respectively. Higher tumor stage (T3/T4), the presence of PNI, and time from surgery >45 days were significant predictive factors of worse loco-regional control in multivariate analysis (p=0.02, p=0.04, and p=0.02). There were 17 local recurrences: 11 (64%) were considered as infield, 4 (24%) as marginal, and 2 (12%) as outfield. There were 9 regional recurrences only, 8 (89%) were considered as infield, and 1 (11%) as outfield. The 1- and 2-year disease-free survival (DFS) rates were 78.9% and 71.8% respectively. The 1- and 2-year overall survival (OS) rates were 88.6% and 80% respectively. Higher tumor stage (T3/T4) and the presence of ENE were the two prognostic factors significantly associated with worse DFS and OS in multivariate analysis. Conclusion: Our outcomes for postoperative VMAT for oral cavity and oropharyngeal cancers are encouraging, with high rates of loco-regional control. However, the management of ENE still seems challenging.
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BACKGROUND: Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. METHODS: This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. DISCUSSION: The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/ . Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022.
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Carcinoma de Células Escamosas , Ácidos Nucleicos Livres , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas/patologia , DNA Complementar , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Estudos Multicêntricos como Assunto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos ProspectivosRESUMO
BACKGROUND: To assess the impact of nutritional status on tolerance to induction chemotherapy by docetaxel, cisplatin and 5-fluorouracil (ICT) in head and neck cancer (HNC). METHODS: Ninety-two HNC patients were included. Toxicity was assessed according to common terminology criteria for adverse events. Nutritional status was assessed by body mass index (BMI), serum albumin, nutritional risk index (NRI), and CT scan (skeletal muscle mass index [SMI] at the first lumbar vertebral level). RESULTS: Before treatment, average BMI was 22.7 ± 4.6 kg/m2 , serum albumin 38.7 ± 5.8 g/L, NRI 97.6 ± 10.6, and SMI 36.4 ± 7.9 cm2 /m2 . After treatment, BMI was 23 ± 4.5, serum albumin 30.2 ± 7.1, and NRI 88.1 ± 9.2. During ICT, 52 (62%) patients developed at least one toxicity ≥ Grade 3. Pre-treatment SMI was the only predictive factor of toxicity irrespective of BMI (p = 0.04). CONCLUSION: Low skeletal muscle mass is a predictive factor of toxicity to ICT in HNC.
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Neoplasias de Cabeça e Pescoço , Quimioterapia de Indução , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Quimioterapia de Indução/efeitos adversos , Músculo Esquelético/diagnóstico por imagemRESUMO
OBJECTIVES: To determine the importance of nutritional status, social status, and inflammatory status in the prognosis of head and neck cancer. STUDY DESIGN: Single-center retrospective study of prospectively collected data. SETTING: Tertiary referral center. METHODS: Ninety-two consecutive patients newly diagnosed for cancer of the upper aerodigestive tract without metastases were assessed at time of diagnosis for several prognostic factors. Nutritional status was assessed by the nutritional risk index, social status by the EPICES score, and inflammatory status by the systemic inflammatory response index. The primary endpoint was overall survival. RESULTS: In multivariable analysis, the main prognostic factors were the TNM classification (hazard ratio [HR] = 3.34, P = .002, for stage T3-4), malnutrition as assessed by the nutritional risk index (HR = 3.64, P = .008, for severe malnutrition), and a systemic inflammatory response index score ≥1.6 (HR = 3.32, P = .02). Social deprivation was not a prognostic factor. CONCLUSION: Prognosis in head and neck cancer is multifactorial; however, malnutrition and inflammation are important factors that are potentially reversible by early intervention.
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Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Inflamação/complicações , Estado Nutricional , Status Social , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Neutrófilos , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The standard care for HER2-positive breast cancer is chemotherapy plus a HER2-directed therapy. This can lead to treatment-induced cardiotoxicity. On the other hand, the practice of physical activity is known to improve cardiac function; thus HER2-positive breast cancer patients could draw particular benefit from physical activity during treatment. However, at the time of diagnosis for breast cancer, the majority of patients are insufficiently active according to physical activity recommendations of World Health Organisation, and it is difficult to remain or become active during the treatment. There is a lack of data in the literature on the optimal program to propose to patients to encourage them to be active during treatment. The aim of our study is to assess the feasibility of a home-based physical activity program during neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer. METHODS: The APACAN2 study is a single-centre, non-randomized interventional trial. Patients with HER2-positive breast cancer treated with anthracycline-based neoadjuvant chemotherapy and trastuzumab are eligible for enrolment. The supervised home-based physical activity program takes place during neoadjuvant chemotherapy (NACT). It combines aerobic and strengthening exercises. The primary endpoint is the proportion of patients reaching the international physical activity recommendations, i.e. 150 minutes of moderate-intensity activity per week at the end of NACT. The study started in April 2018 and seventy patients are expected to be recruited. DISCUSSION: In the literature, the majority of studies on practice of physical activity in breast cancer focus on adjuvant chemotherapy or on the period after the end of treatment. To the best of our knowledge, the APACAN2 study is the first to evaluate a home-based physical activity program during neoadjuvant chemotherapy for HER2-positive breast cancer. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02963363, registered on July 11, 2016. Identifier with the French National Agency for the Safety of Medicines and Health Products N°ID RCB 2016-A01344-47, registered in August 2016. Protocol: version 8, 24 February 2021.
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BACKGROUND: For patients with non-epidermal non-small-cell lung cancer (NSCLC), molecular alterations should always be investigated, especially in non-smokers, who have a very high frequency of targetable alterations (EGFR 52%; ALK 8% in particular). MET exon 14 alterations are identified in 3-4% of NSCLCs and MET gene amplification and high protein expression are associated with a poor prognosis. The French recommendations only authorize the use of capmatinib and crizotinib if the mutation concerns exon 14. However, several different types of mutation in exon 14 of MET and its flanking introns can induce a jump in exon 14, activate the MET gene and thus be sensitive to anti-MET tyrosine kinase inhibitors. CASE SUMMARY: This case concerns a 76-year-old Caucasian male with a medical history including idiopathic thrombocytopenic purpura, chronic myelomonocytic leukemia (CMML), atrial fibrillation, arterial hypertension, obesity (BMI 36kg/m2), and a 5-10 pack-per-year smoking history. A left upper lobe pulmonary nodule of 12.4 mm was discovered in March 2019. The patient received adjuvant chemotherapy with carboplatin AUC 5 and vinorelbine 25.00 mg/m2. At the end of the adjuvant treatment, the patient was in complete remission for 5 months. In February 2020, the CT scan revealed a mediastinal lymph node progression. A complementary molecular analysis was realized on the initial surgical specimen. A c.3082+3A>T mutation in the MET gene was identified. This mutation confers susceptibility to anti-MET tyrosine kinase inhibitors. Treatment with crizotinib was initiated with an initial dose of 250 mg/day for 15 days and then increased to 250 mg twice a day. After 7 months of treatment with crizotinib, the disease was still stable according to RECIST 1.1. CONCLUSION: We report here the original case of a patient presenting a lung adenocarcinoma with an intron 14 mutation and having a durable TKI response.
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BACKGROUND: Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancers but has no specific therapy. While TNBC may be more sensitive to chemotherapy than other types of breast cancer, it has a poor prognosis. Most TNBC relapses occur during the five years following treatment, however predictive biomarkers of metastatic relapse are still lacking. High tumour-infiltrating lymphocytes (TILs) levels before and after neo-adjuvant chemotherapy (NAC) are associated with lower relapse risk and longer survival but TILs assessment is highly error-prone and still not introduced into the clinic. Therefore, having reliable biomarker of relapse, but easier to assess, remains essential for TNBC management. Searching for such biomarkers among serum/plasma proteins, circulating tumoral DNA (ctDNA) and blood cells appear relevant. METHODS: This single-centre and prospective study aims to discover predictive biomarkers of TNBC relapse and particularly focuses on plasma proteins. Blood samples will be taken at diagnosis, on the day of first-line or post-NAC surgery, on the day of radiotherapy start, then 6 months and one year after radiotherapy. A blood sample will be taken at the time of metastatic relapse diagnosis. Blood samples will be used for circulating protein quantification, blood cell counts and circulating tumour DNA quantification. A tumour RNA signature, based on the analysis of the RNA expression of 6 genes, will also be tested from the initial biopsy taken routinely. In NAC patients, TILs quantity will be assessed on TNBC pre-treatment biopsy and surgical specimen. ETHICS AND DISSEMINATION: INSTIGO belongs to category 2 interventional research on humans. This study has been approved by the SUD-EST IV ethics committee and is conducted in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study findings will be published in peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04438681.
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Umbilical skin metastases (or Sister Mary Joseph nodules) are rare. Their presence typically indicates the late manifestation of deep-seated abdominopelvic malignancy. They occur mainly in gynecological cancers, and gastrointestinal cancers in men. The most common histology is adenocarcinoma (â¼75% of cases), but it can also rarely be squamous cell or undifferentiated carcinoma. These metastases can be present at diagnosis or appear at disease recurrence, and are associated with a very poor prognosis with an average survival of 11 months. We report the clinical case of a 58-year-old man with metastatic pancreatic adenocarcinoma and umbilical cutaneous metastasis after receiving first-line chemotherapy. The diagnosis was established upon liver biopsy in July 2019, after the patient presented with a complaint of transfixing abdominal pain. The first-line treatment consisted of six cycles of modified FOLFIRINOX chemotherapy. However, in November 2019, computed tomography (CT) scan showed disease progression. Second-line treatment with gemcitabine (Gemzar®) led to a 16% decrease in target lesions. During the fourth cycle, three periumbilical indurated nodules appeared. After six cycles, skin infiltration had increased, and the patient reported his abdominal pain had intensified. Reassessment by CT scan showed an increase in both hepatic and peritoneal disease progression. Third-line treatment with FOLFIRI, started on April 15, 2020, could not control the disease, leading to greater induration and subcutaneous infiltration, which were responsible for the increased pain and ultimate death. Umbilical skin metastases are rare, and they are associated with advanced metastatic disease and a very poor prognosis. Cases reporting Sister Mary Joseph nodules are needed to better understand the conditions and mechanisms of their appearance and dissemination.
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BACKGROUND: The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC). METHODS: Between June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities. RESULTS: Eighty-nine patients (79%) were male; the median age was 58 years [32-71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03). CONCLUSIONS: TPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimioterapia de Indução/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Taxoides/farmacologia , Taxoides/uso terapêuticoRESUMO
BACKGROUND: Thymic epithelial carcinomas are rare and have a poor prognosis. Treatment of thymic epithelial carcinoma is multimodal and includes surgery, post-operative radiation therapy, adjuvant and neoadjuvant chemotherapy, or exclusive chemotherapy based on disease resectability. However, there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma. CASE SUMMARY: A 45-year-old Caucasian male, with no past medical history, presented with hepatalgia and a cervical mass. A computed tomography (CT) scan showed multiple suspect lesions in the lungs, liver, and anterior mediastinum associated with mediastinal and cervical adenopathy. CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed, confirming the histopathology of thymic epithelial carcinoma. Management consisted of several chemotherapy regimens and radiation therapy, administered between April 2016 and December 2018. The patient achieved complete metabolic response. Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse, with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes. Intravenous pembrolizumab (200 mg, every 3 wk) was administered after two prior systemic therapies. The patient's response to treatment was last documented on March 5, 2020. CONCLUSION: Pembrolizumab was successful in treatment of a patient with programmed death-ligand 1-negative metastatic thymic carcinoma, pretreated with chemotherapy.
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BACKGROUND: Triple negative breast cancer affects 10% to 20% of all women diagnosed with breast cancer. Due to its characteristics, treatment strategies are limited and metastatic recurrences are common in the first 5 years after treatment. However, not all patients affected by this disease develop metastases. Tumor-infiltrating lymphocytes have shown to be reliable predictive biomarkers of treatment response and metastatic recurrences. However, we need to develop simpler and faster ways to predict response to cytotoxic treatment and the possibility of eventual cancer relapse by identifying new biomarkers. Recently, new studies are emerging, suggesting a predictive role of circulating blood cells in different types of cancer. In this study, we will assess the correlation between tumor-infiltrating lymphocytes and different elements of the blood count in patients diagnosed with triple negative breast cancer. METHODS: The main objective of this study is to evaluate the correlation between the peripheral neutrophil-to-lymphocyte ratio and the amount of tumor-infiltrating lymphocytes, assessed in triple negative breast cancer patients at diagnosis. Secondary objectives include evaluation of the correlation between tumor-infiltrating lymphocytes at diagnosis and the baseline absolute neutrophil, lymphocyte, and platelet counts, as well as the platelet-to-lymphocyte ratio. The triple negative breast cancer patients will be enrolled in the PERCEPTION trial during the first year after the treatment completion. Two supplementary blood tests, at 12 months after the end of treatment and at the time of the first metastatic recurrence, will be performed. DISCUSSION: The discovery of new prognostic and predictive biomarkers is crucial for triple negative breast cancer. We set up the PERCEPTION clinical trial in order to evaluate certain blood counts as early biomarkers and to assess their correlation with tumor-infiltrating lymphocytes. Demonstration of comparative predictive and/or prognostic capacities of peripheral blood counts and tumor-infiltrating lymphocytes would allow introduction of the former as simple and cheap biomarkers in triple negative breast cancer patient management. TRIAL REGISTRATION: The PERCEPTION study has been registered in the French National Agency of Medical Security registry on the 2nd of July 2019 under the number 2019-A01861-56 and in the ClinicalTrials.org registry under the number NCT04068623.
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Plaquetas/metabolismo , Neoplasias da Mama/sangue , Linfócitos do Interstício Tumoral/metabolismo , Neutrófilos/metabolismo , Neoplasias de Mama Triplo Negativas/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto JovemRESUMO
Introduction: Patient-derived xenografts (PDX) can be used to explore tumour pathophysiology and could be useful to better understand therapeutic response in breast cancer. PDX from mammary tumours are usually made from metastatic tumours. Thus, PDX from primitive mammary tumours or after neoadjuvant treatment are still rare. This study aims to assess the feasibility to establish xenografts from tumour samples of patients with triple negative or luminal B breast cancer in neoadjuvant, adjuvant or metastatic setting. Methods: XENOBREAST is a single-centre and prospective study. This feasibility pilot trial aims to produce xenografts from tumour samples of patients with triple negative or luminal B breast cancer. Patient enrolment is expected to take 3 years: 85 patients will be enrolled and followed for 28 months. Additional blood samples will be taken as part of the study. Surgical specimens from post-NAC surgery, primary surgery or surgical excision of the metastases will be collected to establish PDX. Histomolecular characteristics of the established PDX will be investigated and compared with the initial histomolecular profile of the collected tumours to ensure that they are well-established. Ethics and dissemination: XENOBREAST belongs to category 2 interventional research on the human person. This study has been approved by the Sud Méditerranée IV - Montpellier ethics committee. It is conducted notably in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study data and findings will be published in peer-reviewed medical journals. We also plan to present the study and all data at national congresses and conferences. Registration: ClinicalTrials.gov ID NCT04133077; registered on October 21, 2019.