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BACKGROUND: Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors (AI). This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration. METHODS: This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an AI. The primary safety endpoint was to assess serum estradiol elevation. The primary efficacy endpoint was sexual function improvement, assessed by the Female Sexual Function Index questionnaire. RESULTS: We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment before completion, mostly due to logistical difficulties related to the COVID-19 pandemic. All patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the undertaken measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p < 0.001), with the greatest improvement observed between the second and third months. CONCLUSIONS: Our findings suggest that topical testosterone seems to be safe and may be effective in improving sexual function in patients on ovarian suppression and AI. TRIAL REGISTRATION: The project was submitted and approved through the hospital's SGPP platform in 11/26/2019 (Project No. SGPP 393819) and CAAE (Research Ethics Committee) (CAAE No 25609719.5.0000.007).
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Testosterona , Humanos , Femenino , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Testosterona/administración & dosificación , Testosterona/sangre , Persona de Mediana Edad , Adulto , Proyectos Piloto , Administración Tópica , Resultado del Tratamiento , Estradiol/administración & dosificación , Estradiol/efectos adversos , COVID-19 , Premenopausia , Disfunciones Sexuales Fisiológicas/etiología , Ovario/efectos de los fármacos , Ovario/metabolismo , SARS-CoV-2RESUMEN
Comprehensive genomic profiling is highly recommended for treatment decision in nonsquamous, non-small cell lung cancer (NSCLC). However, rare genomic alterations are still being unveiled, with scarce data to guide therapy. Herein, we describe the treatment journey of a 56-year-old, never-smoker Caucasian woman with a metastatic NSCLC harboring a CD47-MET fusion, initially classified as a variant of unknown significance. She had undergone 3 lines of therapy over the course of 3 years, including chemotherapy, immunotherapy, and anti-angiogenic therapy. After reanalysis of her next-generation sequencing data in our service, the fusion was reclassified as likely oncogenic. The patient was started with fourth-line capmatinib, with a good tolerance so far and a complete metabolic response in the active sites of disease, currently ongoing for 18 months. In conclusion, we highlight the sensitivity of a novel MET fusion to capmatinib and emphasize the need for comprehensive panels in NSCLC and molecular tumor board discussions with specialized centers when rare findings arise.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-met , Humanos , Femenino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas c-met/genética , Acrilamidas/uso terapéutico , Benzamidas/uso terapéutico , Proteínas de Fusión Oncogénica/genética , Triazinas/uso terapéutico , ImidazolesRESUMEN
OBJECTIVE: Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. METHODS: This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. RESULTS: A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. CONCLUSIONS: PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Pronóstico , Estimación de Kaplan-Meier , Inmunohistoquímica , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , AdultoRESUMEN
ABSTRACT Objective Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. Methods This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. Results A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. Conclusions PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.
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The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.
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Non-small cell lung cancer (NSCLC) is still diagnosed at late stages in Brazil. The availability of newer treatment options has changed patient management, however, few real-world data have been published since then. This is a population-based retrospective cohort study that aims to evaluate the characteristics of stage III/IV NSCLC patients and their journey in the Brazilian private healthcare system. Patients aged ≥18 years, residing in Brazil who had their first medical appointment between 2016 and 2018 were included in the study. The sociodemographic and clinical characteristics of the patients and time intervals of interest were described. A total of 10,394 patients were analyzed. The majority of the patients were male (58.5%) with a median age of 64.0 (IQR = 58.0 - 71.0) years. In relation to characteristics of the disease, most of the tumors were characterized as adenocarcinomas (52.3%) and diagnosed at stage IV (72.2%). Most patients arrived at the hospital with an established NSCLC diagnosis, while 45.7% were diagnosed at the first medical appointment in the hospital or later. For patients who were diagnosed at the first medical appointment or later, a median interval of 15.0 (IQR = 6.0 - 33.0) days was observed between the first medical appointment and the diagnosis. The first treatment was given after a median of 25.0 (IQR = 6.0 - 49.0) days after diagnosis for patients without a prior diagnosis, and 57.0 (IQR: 33.0 - 98.0) days for patients with a prior diagnosis. The most common treatments were chemotherapy alone (33.8%), chemotherapy combined with radiotherapy (21.5%), radiotherapy alone (13.1%), adjuvant or neoadjuvant treatment (9.3%), surgery (3.3%), and immunotherapy (0.7%; alone or combined). At the end of follow-up (September, 2020), 52.3% of the patients had died. Despite having more treatment options in the private sector, data show that there is a need to improve access to technologies.
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INTRODUCTION: Tumor-infiltrating lymphocytes (TIL) is a predictive and prognostic biomarker for breast cancer (BC) HER2-positive and triple negative, but its presence in HER2-low tumors is unknown. We aimed to determine TIL levels in HER2-low tumors and its correlation with other clinicopathologic features. MATERIALS AND METHODS: We retrospectively analyzed all the pathology reports of breast surgeries of a tertiary hospital in Sao Paulo, Brazil, from January 2021 to March 2022. Inclusion criteria were stage I to III invasive BC, and exclusion criteria were nonmalignancies and neoadjuvant therapy. We assumed HER2 categories according to ASCO/CAP guidelines. TILs were defined as absent (0), low (1%-10%), intermediate (11%40%) and high (≥ 41%). Ki-67 levels were categorized as low (up to 19%) and high (≥ 20%). RESULTS: From 272 patients, 198 met the inclusion criteria. Histological grade 3 was found in 10, 19 and 47% of HER2-0, low, and positive tumors (P < .001). HER2-positive tumors had 82.6% of high Ki-67 levels, while HER2-negative and HER2-low showed 25.8% and 31.4% (P = .005). TILs in HER2-0, low, and positive tumors were, respectively, absent in 16.1%, 17.6%, and 8.7%; low in 70.2%, 52.9% and 34.8%; intermediate in 11.3%, 25.5% and 47.8%; and high in 2.4%, 3.9% and 8.7%. There was a statistically significant difference in TILs between HER2-negative versus HER2-positive groups (P < .001), but not between HER2-negative versus HER2-low, or HER2-low versus HER2-positive. CONCLUSION: TILs in HER2-low are marginally higher than HER2-negative, but significantly lower than HER2-positive levels. HER2-low tumors do not seem to significantly differ biologically from HER2-negative tumors.
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Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.
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Neoplasias Pancreáticas , Humanos , Femenino , Masculino , Brasil , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/diagnóstico , Estudios Retrospectivos , Pancreatectomía/métodos , Páncreas/patologíaRESUMEN
Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.
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Carcinoma de Células Escamosas , Úlceras Bucales , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Ganglios Linfáticos , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Comprehensive next-generation sequencing panels are leading to detection of rare gene fusion events. EFGR-RAD51 fusion is a rare oncogenic finding and clinical data for management of this condition is scarce. We report a widely metastatic non-small cell lung cancer in a never-smoker young male patient with sustained near-complete systemic and intracranial response to osimertinib, a third-generation EGFR tyrosine-kinase inhibitor (TKI). We also review the available data of other TKIs in this scenario and underscore the role of comprehensive molecular testing for NSCLC.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acrilamidas , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Compuestos de Anilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Fusión Génica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Recombinasa Rad51/genéticaRESUMEN
ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.
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Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Úlceras Bucales , Anticuerpos Monoclonales Humanizados , Ganglios LinfáticosRESUMEN
Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5-10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2-3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.
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[This corrects the article DOI: 10.3389/fonc.2020.580141.].
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BACKGROUND: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations. METHODS: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells. RESULTS: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes. CONCLUSION: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction.
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Carcinoma Ductal , Neoplasias de las Glándulas Salivales , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Humanos , Persona de Mediana Edad , Receptores Androgénicos , Conductos SalivalesRESUMEN
Salivary gland carcinomas (SGCs) account for <5% of head and neck malignant neoplasms, further subcategorized in over 20 histological subtypes. For the most part, treatment for advanced disease is guided by morphology. SGCs in general respond poorly to a wide array of standard chemotherapy, with short durability, and significant toxicity. More recently, next-generation sequencing provided significant input on the molecular characterization of each SGC subtype, not only improving diagnostic differentiation between morphologically similar tumor types but also identifying novel driver pathways that determine tumor biology and may be amenable to targeted therapy. Among the most common histological subtype is adenoid cystic carcinoma, which often harbors a chromosome translocation resulting in an MYB-NFIB oncogene, with various degrees of Myb surface expression. In a smaller subset, NOTCH1 mutations occur, conferring a more aggressive pattern and potential sensitivity to Notch inhibitors. Salivary duct carcinomas may overexpress Her-2 and androgen receptors, with promising clinical outcomes after exposure to targeted therapies approved for other indications. Secretory carcinoma, previously known as mammary analog secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and make it susceptible to Trk inhibitors. In the present article, we discuss the molecular abnormalities, their impact on tumor biology, and therapeutic opportunities for the most common SGC subtypes and review published and ongoing clinical trials and future perspectives for this rare disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Neumonía/diagnóstico , Anciano , Anciano de 80 o más Años , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Diagnóstico Tardío , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Humanos , Ipilimumab/efectos adversos , Tiempo de Internación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Pulmón/diagnóstico por imagen , Masculino , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/secundario , Metilprednisolona/uso terapéutico , Nasofaringe/virología , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neoplasias Primarias Desconocidas/inmunología , Nivolumab/efectos adversos , Pandemias , Neumonía/tratamiento farmacológico , Neumonía/inmunología , Neumonía Viral/epidemiología , Neumonía Viral/virología , SARS-CoV-2 , Factores de Tiempo , Tiempo de Tratamiento , Tomografía Computarizada por Rayos X , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/inmunología , Neoplasias de la Úvea/secundarioRESUMEN
PURPOSE: Systemic inflammation plays a crucial role in carcinogenesis and progression of pancreatic cancer, due to its influence on tumor angiogenesis, invasion and metastasis. The association of CA 19-9, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can identify patients with different prognoses. METHODS: We reviewed 148 pancreatic cancer patients' charts diagnosed from January 2006 to December 2018 in a tertiary hospital. Cox proportional survival models were used to evaluate the impact of each factor on recurrence-free and overall survival (OS). RESULTS: When assessing risk of relapse, the presence of angiolymphatic invasion was associated with an 80% chance of recurrence in 5 years. Among other factors associated with OS, the estimated risk of death in patients with CA 19-9>300 U/mL was 2.37-fold higher compared to lower values. In addition, the risk of death was 60% and 76% higher in patients with NLR>3 and PLR>150, respectively. Patients within these 3 categories had a median OS of only 7.5 months, lower than all-comer patients with stage IV disease, with median OS estimated at 9.84 months. CONCLUSION: The laboratory variables CA 19-9, NLR and PLR together can contribute to a better stratification of patients with pancreatic adenocarcinoma beyond conventional staging. Prospective initiatives using these factors together can demonstrate different subgroups of patients who benefit from new treatment strategies.