Squamous Cell Carcinoma Of The Larynx Research Articles

Effectiveness and feasibility of selective intra-arterial low dose of cisplatin infusion and concomitant radiotherapy for patients with advanced laryngeal cancer with impaired renal function: A retrospective cohort study.

Chemoradiation therapy with high-dose cisplatin is the standard regimen against advanced squamous cell carcinoma of the larynx (SCC-L). However, patients with renal dysfunction are ineligible for this regimen. We investigated the effectiveness and feasibility of selective intra-arterial low-dose cisplatin infusion and radiotherapy (modified [m]-RADPLAT) for patients with impaired renal function. We retrospectively reviewed the data of 77 patients with SCC-L who received m-RADPLAT. Fourteen and 63 patients had creatinine clearance (CrCl) values of 30 ≤ CrCl < 60 mL/min and ≥60 mL/min, respectively. The m-RADPLAT regimen led to no significant changes in serum creatinine or CrCl values post-treatment. The 5-year local control, overall survival, and laryngectomy-free survival rates of the CrCl < 60 and ≥60 groups were 90.0% and 90.5%, 100% and 81.8%, and 100% and 79.0%, respectively. Grade 3 or higher toxicity rates were not significantly different between the groups. The m-RADPLAT regimen yielded favorable survival rates and clinical outcomes in patients with impaired renal function.

A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx.

The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. All consecutive patients with biopsy-proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow-up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group. The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.

Vocal Cord Function Return After Larynx Preservation is Associated With Recurrence‐Free Probability

ObjectivesVocal cord fixation is one of the main upstaging features of laryngeal cancer. In our previously conducted retrospective study, vocal cord (VC) mobility restoration after chemoradiotherapy was a favorable prognostic variable. In this prospective study, we examined the significance of VC mobility restoration after definitive treatment as a prognostic variable.MethodsIn this prospective cohort study, we enrolled 30 patients with squamous cell carcinoma of the larynx with VC impairment/fixation (T2/3, T4a) who underwent definitive chemoradiotherapy with complete response. Video laryngoscopy before and at 3 months after treatment was used to evaluate VC mobility. The primary endpoint of the study was the local recurrence‐free probability. Secondary endpoints included recurrence‐free probability, disease‐specific survival (DSS), and overall survival (OS).ResultsThe median age of patients was 62 years (IQR 54–67). The primary subsites were the glottis (n = 13) and supraglottis (n = 14). After treatment, 18 (60%) patients had a full recovery of VC mobility, and 12 (40%) patients' VCs were fixed or impaired. Five‐year local recurrence‐free probability was worse in the VC‐impaired group compared to a group with restored VC mobility (46% vs. 85%, p = 0.012). Recurrence‐free probability, OS, and DSS differences were not statistically significant in both groups. VC mobility restoration predicted local recurrence‐free probability on univariable analysis (HR 6.15, 95% CI 1.23–30.6).ConclusionIn this prospective study, we show that the absence of VC mobility restoration is associated with worse local recurrence‐free probability after definitive laryngeal preservation treatment. Patients with persistent vocal cord immobility warrant closer follow‐up to detect recurrence early.Level of EvidenceIII Laryngoscope, 2024

Intra-operative lymphatic mapping and sentinel node biopsy in laryngeal carcinoma using radiotracer injection.

The purpose of this study was to determine the value of sentinel lymph node biopsy (SLNB) in the laryngeal SCC, using intra-operative peri-tumoral injection of Tc-99m-phytate. Patients with biopsy-proven squamous cell carcinoma of the larynx were included. On the day of surgery, after anesthesia induction, suspension laryngoscopy was performed to inject 74MBq/0.4ml Tc-99m-phytate in four aliquots into the sub-mucosal peri-tumoral location. After a 10-min wait, a portable gamma probe was used to locate sentinel nodes. Subsequently, all patients underwent laryngectomy and neck dissection. Both sentinel nodes and non-sentinel nodes were examined using hematoxylin and eosin (H&E) staining. Twenty-six patients with a diagnosis of laryngeal carcinoma were included in the study. The SLN detection rate was 65.4%, with a 100% detection rate in the supraglottic region and a 52.6% detection rate for glottis/transglottic patients. Permanent pathology results showed lymph node involvement in four patients, but only one patient had a negative result in the SLNB, resulting in an overall false negative rate of 25%. The sensitivity of the SLN technique was 75% overall, 100% in the supraglottic region, and 67% in the glottis/transglottic region. The accuracy and feasibility of SLNB may be related to the location of the tumors in the larynx. For supraglottic tumors, the technique seems to be feasible with a low false negative rate. For glottis/transglottic tumors, both the detection rate and false negative rate seem to be suboptimal. Further studies are needed to validate our results.

Papillary thyroid microcarcinoma revealed during surgical treatment of squamous cell carcinoma of the larynx

Papillary thyroid microcarcinoma revealed during surgical treatment of squamous cell carcinoma of the larynx

Total laryngectomy

Knowledge of the total laryngectomy is essential for the head & neck surgeon. While there are many indications for the procedure, it is most commonly performed for advanced squamous cell carcinoma of the larynx. This article will review common indications, basic technique, and complications of the total laryngectomy.

Fine-needle aspiration diagnosis of secondary malignant tumors of the thyroid gland: A single-institution experience of 17 cases.

Fine-needle aspiration (FNA) is the most commonly used preoperative pathological diagnostic tool for thyroid tumors. Secondary malignant tumors of the thyroid gland account for less than 3% of all thyroid malignancies. The aim of this study was to investigate the types and cytopathological features of secondary thyroid tumors, evaluate diagnostic pitfalls in FNA. Cases of secondary thyroid tumors diagnosed in the Department of Pathology of Shaanxi Provincial People's Hospital were collected, and their clinical data, cytologic features, immunohistochemical results, and histopathological diagnoses were summarized. The study included 17 cases (8 males and 9 females) with a mean age of 60.4 ± 9.4 years (range, 45-83 years). Six cases had a known history of primary malignancy prior to FNA aspiration diagnosis. The most common organs of origin were the lungs (5 cases, 3 adenocarcinoma, and 2 small-cell carcinoma) and esophagus (5 cases, 3 squamous-cell carcinoma, 1 adenocarcinoma, and 1 small-cell carcinoma). The next most common was squamous-cell carcinoma of the larynx (3 cases), and gastric tumor (2 cases), including 1 lymphoma and 1 adenocarcinoma. Cell blocks and immunohistochemistry were performed in 12 of these cases. Comparison of the impact of positive history and IHC availability on the accuracy of pathologic diagnosis showed that both were statistically significant. FNA is an effective means of diagnosing secondary malignancies of the thyroid, in which knowledge of the patient's history of malignancy is essential, and the use of cell blocks and immunohistochemistry helps to clarify the pathological diagnosis.

Metastatic deposit of Squamous cell carcinoma of larynx presenting as acute intestinal obstruction: An atypical presentation with literature review

ABSTRACT Laryngeal squamous cell carcinoma (SCC) is the major subtype, accounting for 90% of cancers at this site. While it has a propensity for locoregional spread to cervical nodes, distant metastasis is seen less frequently and mostly to the lungs, bones, and liver, with an overall incidence of 6.5–7.3%. We hereby report a case of a 61-year-old male previously treated for SCC of the larynx, presenting with an acute intestinal obstruction with the presence of metastatic deposits of SCC in the omentum.

Transoral robotic supraglottic laryngectomy: Long-term functional and oncologic outcomes

ObjectivesMinimally invasive transoral organ preservation surgeries are being increasingly used for supraglottic tumors. This study investigates the long-term functional and oncologic outcomes of transoral robotic supraglottic laryngectomy (TORS-SGL). Materials and methodsTwenty-three patients with supraglottic laryngeal cancer who underwent TORS-SGL between 2012 and 2015 at a tertiary referral hospital were retrospectively analyzed with at least 5 years of follow-up. The head and neck tumor council and the multidisciplinary oncological board decided whether the patients were suitable for robotic surgery, and the necessity of adjuvant radiotherapy or chemotherapy. Inclusion criteria was histopathological diagnosis of squamous cell carcinoma of the larynx. ResultsTwenty-one patients with T1-T3 supraglottic squamous cell carcinoma were included in this study. Mean follow-up was 48.8 months. Local control was 94.4 % at 2 years and 85.9 % at 5 years. Disease-free survival and overall survival were 85.7 % and 81 % at 2 years and 69.3 % and 57.1 % at 5 years, respectively. There was no permanent tracheostomy or prolonged swallowing dysfunction among patients. Age, perineural and lymphovascular invasion were found to be risk factors affecting overall survival. ConclusionTORS-SGL is a feasible, safe and reliable approach with excellent functional results for T1, T2, and selected T3 supraglottic tumors, providing acceptable long-term oncologic results when compared to alternative treatment modalities.

Translated article] Complete Resolution of Bazex Syndrome After Surgical Treatment of Squamous Cell Carcinoma of the Larynx

Translated article] Complete Resolution of Bazex Syndrome After Surgical Treatment of Squamous Cell Carcinoma of the Larynx

Multiple primary cancers: a case report and literature review

The fortuitous discovery of synchronous double primary cancers of the lung and stomach is relatively rare, but the discovery of triple primary cancers in one patient remains exceptional. The discovery of triple primary cancers in a single patient remains exceptional. This coexistence corresponds to the syndrome of multiple primary malignancies or multiple primary cancers (MPC). We present a case of synchronous association of squamous cell carcinoma of the lung and gastric adenocarcinoma with a history of mature squamous cell carcinoma of the larynx.

Salvage total laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: Validated prognostic nomograms predicting oncological outcomes.

Salvage total laryngectomy (STL) is a preferred treatment for patients with residual, recurrent, and second primary squamous cell carcinoma of the larynx/hypopharynx after (chemo)radiation. To individually estimate postoperative oncological outcomes, we designed and validated prognostic nomograms. We used a dataset of 290 patients who underwent STL. Nomograms predicting 2- and 5-year OS, DFS, and DSS were developed, using variables which are identified pre- or postoperatively. The nomograms were externally validated on a dataset of 109 patients. The nomograms based on postoperative variables performed better than those based on preoperative variables (OS: C = 0.68 vs. 0.64; DFS: C = 0.70 vs. 0.64; DSS: C = 0.74 vs. 0.64). The nomogram predicting DSS based on postoperative variables performed best. The presented prognostic nomograms for predicting oncological outcomes in patients who undergo STL are tools which allow for a reliable prognostic assessment.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Oto-rhino-laryngological and cervico-maxillofacial pathologies among hospitalized older patients: epidemiological, diagnostical and therapeutical aspects in Lomé, Togo

In developing countries, 10% of the population is over 60 years old and this proportion is increasing rapidly. The general objective of this study was to describe the profile and management of the elderly subject aged 60 and over, hospitalized in the ENT (Ear, Nose and Throat) and Head/Neck surgery department of the Sylvanus Olympio University Hospital in Lomé, from 2012 to 2021. Retrospective descriptive study. After reviewing the files, selection of patients aged 60 and over, regardless of sex, and hospitalized for an ENT pathology from January 2012 to December 2021. Not included in our study were files of elderly subjects hospitalized but whose age was imprecise, or empty or very incomplete files. A total of 296 cases were included, representing 6.7% of the department's activities. The mean age of the patients was 72 ± 7.3 years with extremes of 60 and 95 years. The age group 6069 years represented 59.5%. The sex ratio M/F was 0.92. Infectious/inflammatory lesions were found in 138 patients (46.6%) including 38.9% of acute cellulitis of dental origin, and tumors were found in 135 patients (45.6%). Tumors were malignant in 59 patients (43.7%) and benign in 76 patients (56.3%). Thyroid was the site of 46 (60.5%) benign lesions and larynx of 29 (49.2%) malignant lesions. Poor oral hygiene, use of non-steroidal anti-inflammatory drugs, diabetes and the combination of smoking and alcohol were the factors favoring the occurrence of acute cellulitis of dental origin in 89.6%, 80.9%, 20.0% and 2.6% of cases respectively (p<0.001). The combination of smoking and alcohol was a factor favoring the occurrence of malignancy in 39% (p<0.001). Surgical treatment was performed in 234 patients (79.1%). With a case lethality rate of 21%, acute cellulitis of dental origin was the leading cause of death (p<0.001). The most frequent pathologies of the ENT sphere in the elderly in our tropical context were infectious and tumoral, largely dominated by acute cellulitis of dental origin, thyroid adenoma and squamous cell carcinoma of the larynx. Despite the tendency to balance infectious and tumoral pathologies, the proportion of acute cellulitis of dental origin remains twice as high as that of malignant tumors. It contrasts with data from other sub-Saharan series where tumoral pathology remains predominant in the elderly. It is important to provide dental care assistance to the elderly and to advocate for the development of geriatrics and access to universal health coverage for the elderly in Togo.

Adaptive FDG-PET/CT guided dose escalation in head and neck squamous cell carcinoma: Late toxicity and oncologic outcomes (The ADMIRE study)

PurposeTo report on the late toxicity and local control (LC) of head and neck cancer patients treated with adaptive FDG-PET/CT response-guided radiotherapy (ADMIRE) with dose escalation (NCT03376386). Materials and methodsBetween December 2017 and April 2019, 20 patients with stage II-IV squamous cell carcinoma of the larynx, hypopharynx or oropharynx were treated within the ADMIRE study where FDG-PET/CT response-guided (Week 2&4) dose escalation was applied (total dose 70–78 Gy). Cisplatin or cetuximab was added to radiotherapy in case of T3-4 and/or N2c disease. To compare the LC and late toxicity of the study population, we used an external control group (n = 67) consisting of all eligible patients for the study (but not participated). These patients were treated in our institution during the same period with the current standard of 70 Gy radiotherapy. To reduce the effect of confounding, logistic regression analyses was done using stabilized inverse probability of treatment weighting (SIPTW). ResultsAfter median follow-up of 40 and 43 months for the ADMIRE and control groups, the 3-year LC-rates were 74% and 78%, respectively (adjusted HR after SIPTW 0.80, 95 %CI 0.25–2.52, p = 0.70). The incidences of any late G3 toxicity were 35% and 18%, respectively. The adjusted OR for any late G3 toxicity was 5.09 (95 %CI 1.64–15.8, p = 0.005), for any late G ≥ 2 toxicity was 3.67 (95 %CI 1.2–11.7, p = 0.02), for persistent laryngeal edema was 10.95 (95% CI 2.71–44.29, p = 0.001), for persistent mucosal ulcers was 4.67 (95% CI 1.23–17.7, p = 0.023), and for late G3 radionecrosis was 15.69 (95 %CI 2.43–101.39, p = 0.004). ConclusionGiven the comparable LC rates with increased late toxicity in the ADMIRE group, selection criteria for future adaptive dose escalation trials (preferably randomized) need to be refined to include only patients at higher risk of local failure and/or lower risk of severe late toxicity.

Perineural Invasion of Superior and Inferior Laryngeal Nerves in Advanced Stage Squamous Cell Carcinoma of the Larynx: A Case Series and Review.

To evaluate bilateral superior and recurrent laryngeal nerves for tumor spread in patients of advanced-stage laryngeal carcinoma undergoing surgical resection. A prospective study was conducted including biopsy-proven cases of laryngeal squamous cell carcinoma (SCC) that were planned for total laryngectomy. Patients with metachronous or synchronous SCC were excluded from the study. All patients underwent total laryngectomy, where both superior and recurrent laryngeal nerves were harvested along with the specimen, and the proximal ends of the nerves were marked for reference. Perineural invasion (PNI) was assessed in nerves within the tumor and in bilateral extra-laryngeal nerves. The study included 22 patients with a mean age of 58 years. Intra-tumoral PNI was found in 7 of the 22 cases (32%). The free nerve margins of superior and recurrent laryngeal nerves, which were examined from proximal to distal orientation, showed no tumor infiltration in any of the cases. Perineural invasion of minor nerves constitutes a major pathway of spread. On the contrary, invasion of superior or recurrent laryngeal nerves does not constitute a route for tumor spread. Hence, there is no need to extend the surgical boundary for total laryngectomy to include these major nerves separately.

Superior loco-regional control after primary surgery compared to chemo-radiotherapy for advanced stage laryngeal cancer.

The optimal strategy to treat loco-regionally advanced squamous cell carcinoma of the larynx (LSCC) remains to be defined. The goal of this single institution retrospective study was to report on oncologic outcome of advanced LSCC treated with curative intent. Patients diagnosed and treated for stage T3-T4a LSCC between 2001 and 2014 were retrospectively analyzed. Time-to-event endpoints were calculated beginning from the date of histologic diagnosis, which were analyzed with log-rank test and Cox proportional hazard models. The cohort was divided into two subgroups: primary radiotherapy with concomitant cisplatin (CRT) (n=30, 38%) and primary surgery (n=48, 62%). Median follow-up was 56 months. Locoregional control (LRC) for the primary surgery and CRT were 95% and 50% in 5 years, respectively (p<0.01). Progression free survival (PFS) for the primary surgery and CRT were 61% and 38% in 5 years, respectively (p=0.23). The overall survival (OS) after primary surgery and CRT in 5 years were 63% vs. 65%, respectively (p=0.93). The 5-years LRC was significantly superior after surgery compared to RT for cT3 primaries (100% vs 50%, p= 0.0022). No significant differences were observed in the remaining subgroups regarding cT stage and PFS or OS. Our series demonstrated superior LRC after primary surgery followed by risk-adapted adjuvant (C)RT compared to primary CRT in cT3 LSCC, but no significant difference in PFS or OS in locally-advanced LSCC. The optimal patient selection criteria for the ideal treatment for loco-regionally advanced LSCC still needs to be defined.

Elevated Tumor Cell-Intrinsic STING Expression in Advanced Laryngeal Cancer

Laryngeal cancer is the second most common malignancy of the head and neck, worldwide. Immunotherapy targeting checkpoint inhibitors has been approved for the treatment of patients with recurrent or metastatic laryngeal cancer but has a relatively low response rate and outcomes that leave many patients underserved. Targeting the cGAS–STING signaling pathway can potentially improve the activation of immune effector cells, although its role in the development and progression of laryngeal cancer has not yet been investigated in depth. Fifty-nine tumor samples from patients with pathologically confirmed squamous cell carcinoma of the larynx, stage I–IV non-metastatic disease, who were treated at the University Hospital of Split, were immunohistochemically stained for the expression of STING, cGAS, CD8, CD68, and CD163. Elevated tumor cell-intrinsic STING expression was positively associated with stage IV (p = 0.0031), pT3, and pT4 laryngeal cancers (p = 0.0336) as well as with higher histological grades (G2 and G3) (p = 0.0204) and lymph node-positive tumors (p = 0.0371). After adjusting for age, sex, location, and cGAS expression, elevated STING expression was significantly associated with stage IV cancer in a multiple logistic regression model (β = 1.849, SE = ±0.8643, p = 0.0324). Elevated STING expression represents a potentially favorable predictive biomarker for new therapeutic approaches involving STING agonists combined with immunotherapy and DNA-damaging agents (radiotherapy, cisplatin, and PARP inhibitors) in laryngeal cancer.

Síndrome de Bazex con resolución completa tras tratamiento quirúrgico de carcinoma epidermoide de laringe

Síndrome de Bazex con resolución completa tras tratamiento quirúrgico de carcinoma epidermoide de laringe

A single-arm, multi-institutional, phase 2 study of a pembrolizumab-based organ preservation strategy for locally advanced larynx cancers: SMART-KEY (LACOG 0720) trial.

TPS6111 Background: Standard treatments for locally advanced larynx cancers include concurrent cisplatin/radiation therapy, or induction chemotherapy followed by radiation therapy alone, with the goal of organ preservation. Both strategies have been shown to achieve similar laryngectomy-free survival (LFS), but failed to improve overall survival (OS) compared with radiation therapy alone or surgery followed by radiation therapy. Although cisplatin given concurrently with radiation therapy is commonly used for organ preservation, there are concerns regarding long-term outcomes, such as late toxicities. Pembrolizumab with chemotherapy has been shown to improve OS in recurrent/metastatic head and neck squamous cell carcinomas (HNSCCs). Additionally, pembrolizumab combined with radiation therapy has been shown to be safe in locally advanced HNSCC. LACOG 0720 is designed to evaluate a pembrolizumab-based, cisplatin-free, and concurrent chemoradiation therapy-free regimen for larynx preservation, in an attempt to improve outcomes and avoid late toxicities. Methods: LACOG 0720 is a phase 2, single-arm, multicentric trial assessing patients with newly diagnosed squamous cell carcinoma of the larynx (glottic or supraglottic) and clinical stages III, IVA, or IVB (AJCC 8th Ed.). Patients with large volume T4 disease (invasion through the cartilage or extension &gt; 1 cm to the base of the tongue) or T1 disease are excluded. Patients receive 3 cycles of induction chemo-immunotherapy (carboplatin AUC6, paclitaxel 175 mg/m², and pembrolizumab 200 mg, IV every 21 days [q21D]), followed by concurrent radioimmunotherapy (Intensity-modulated radiation therapy with pembrolizumab 200 mg IV q21D for 3 cycles), followed by consolidation immunotherapy (pembrolizumab 200 mg IV q21D for 11 cycles). The primary endpoint is two-year LFS rate. Secondary endpoints include two-year larynx dysfunction-free survival, OS, overall response rate, short-term and long-term toxicities, causes of death, patterns of failure, and quality of life. Predictive biomarkers of response and survival will be evaluated as exploratory analysis. The sample size was calculated based on the primary endpoint. Using the Chi-square Test for One Proportion and considering a one-sided 10% significance level, 39 patients are needed to achieve 80% power to detect the difference between the null hypothesis; that the true laryngectomy-free survival at two years is 59%, and the alternative hypothesis that the laryngectomy-free survival at two years is 75%. From Feb 2022 to Feb 2023, 24 patients were enrolled in 10 Brazilian centers. Results are expected in July 2024. NCT04943445. Clinical trial information: NCT04943445 .