Carcinomatosis peritoneal en cáncer de pulmón: revisión de la literatura con reporte de caso / Peritoneal Carcinomatosis in Lung Cancer: Literature Review with a Case Report

En Colombia, para 2020, el cáncer de pulmón se reportó como la segunda neoplasia con mayor incidencia y la primera con mayor tasa de mortalidad según las cifras del minis-terio de salud de Colombia. El compromiso peritoneal en el cáncer de pulmón es algo extremadamente raro, se considera <1%. A continuación, exponemos un caso de car-cinomatosis peritoneal en cáncer de pulmón en un hospital en la ciudad de Bogotá. Se incorpora una posterior revisión descriptiva de la literatura de los casos clínicos de car-cinomatosis peritoneal en cáncer de pulmón reportados en la literatura mundial en los últimos 20 años, con el objetivo de resumir las principales características de estos pa-cientes que permiten plantear hipótesis de su enfoque terapéutico y pronóstico

In Colombia for 2020, lung cancer was reported as the fifth neoplasm with the highest incidence and the second with the highest mortality rate. Peritoneal involvement in lung cancer is extremely rare, it is considered <1%. Next, we present a case of peritoneal car-cinomatosis in lung cancer in Bogotá, with a subsequent literature review of the litera-ture of clinical cases of peritoneal carcinomatosis in lung cancer reported in the world li-terature in the last 20 years. The aim is to summarize the main characteristics of these patients that allow to hypothesize their prognostic and therapeutic approach

Papel de la persona navegadora del paciente en el cáncer de pulmón / The Role of the Navigator Person for a Patient with Lung Cancer

Introducción: la medicina basada en el valor ha logrado mejorar la calidad de atención del paciente y/o la satisfacción de las personas, reduciendo costos y obteniendo mejores resultados. Se apoya sobre tres pilares básicos: la medicina basada en la evidencia, la atención centralizada en el paciente, y la sustentabilidad. Sin embargo, existen pocas publicaciones sobre la estrategia de personas navegadoras para pacientes con cáncer de pulmón, que podrían ser una herramienta clave para brindar apoyo, asegurando que tengan acceso al conocimiento y los recursos necesarios a fin de completar la vía de atención clínica recomendada. Estado del arte: se trata de una intervención en salud cuyo objetivo principal es lograr vencer las barreras relacionadas con la atención (p. ej., logísticas, burocrático-administrativas, de comunicación y financieras) para poder mejorar la calidad y el acceso a la salud en el marco de la atención del cáncer. Estas personas cumplen un papel de guía para pacientes durante el proceso de diagnóstico y tratamiento activo. Su labor consiste en vincular al paciente con los proveedores clínicos, brindar un sistema de apoyo, asegurar un acompañamiento individualizado, garantizar que tengan acceso al conocimiento y a los recursos necesarios para completar el seguimiento y/o tratamiento adecuado. Discusión/Conclusión: indudablemente, es un elemento cada vez más reconocido en los programas de cáncer, centrado en el paciente y de alta calidad. Su implementación será de especial interés en la Unidad de Práctica Integrada para personas con cáncer de pulmón. (AU)

Introduction: Value-based medicine has succeeded in improving the quality of patient care and or patient satisfaction, reducing costs, and obtaining better outcomes. It rests on three fundamental pillars: evidence-based medicine, patient-centered care, and sustainability. However, there are few publications on the people navigator strategy for lung cancer patients, which could be a crucial tool for providing support, ensuring that they have access to the knowledge and resources needed to complete the recommended clinical care pathway. State of the art: It is a health intervention whose main objective is to overcome care-related barriers (e.g., logistical, bureaucratic-administrative, communication, and financial) to improve quality and access to health in the context of cancer care. These individuals play a guiding role for patients during the diagnostic and active treatment process. Their job is to link the patient with clinical providers, provide a support system, ensure individualized accompaniment, and guarantee that they get access to the knowledge and resources necessary to complete the appropriate follow-up and, or treatment. Discussion/Conclusion: Undoubtedly, patient navigators represent an increasingly recognized element of high-quality, patient-centered cancer programs. Its implementation will be of specific interest in the Integrated Practice Unit for people with lung cancer. (AU)

Neumotórax espontáneo persistente como manifestación primaria de sarcoma sinovial pleuropulmonar primario: a propósito de un caso / Persistent spontaneous pneumothorax as a primary manifestation of primary synovial sarcoma of the lung: a case report

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo

Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.

COVID-19 en pacientes oncológicos / COVID-19 in cancer patients

Introducción: La Organización Mundial de la Salud declaró el COVID-19 como una pandemia el 11 de marzo de 2020. El antecedente de cáncer es considerado un factor de riesgo de mortalidad para múltiples padecimientos; la evolución de los pacientes con enfermedades neoplásicas puede verse influida por afecciones sobreañadidas como fue el caso del COVID-19. Objetivo: Caracterizar, desde el punto de vista clínico, a los pacientes oncológicos que ingresaron con COVID-19. Métodos: Se realizó una investigación descriptiva y transversal en pacientes con diagnóstico de enfermedad oncológica ingresados por COVID-19, en el Hospital Universitario Dr. Celestino Hernández Robau, Villa Clara, en el período de enero-diciembre 2021. Se incluyeron en el estudio 78 pacientes con diagnóstico de neoplasia de 5 años o menos de evolución. Resultados: Predominó el sexo masculino y los mayores de 60 años de edad. El 39,7 % de los pacientes presentó cáncer de pulmón o de laringe seguido por cáncer de mama, hemolinfopoyético y colorrectal. El 46,2 % se encontraba en estadio estable y el 29,5 % en paliativo. El 34,6 % de los pacientes recibía tratamiento con quimioterapia en el momento del ingreso. Los fármacos más utilizados fueron: esteroides (85,9 %), interferón alfa (73,1 %) y heparina sódica (55,1 %). Conclusiones: En los pacientes oncológicos hospitalizados con COVID-19, los tumores de pulmón y laringe fueron los más frecuentes, aunque el de mama, próstata y colorrectal, en ese orden, se relacionaron con mayor mortalidad. Los pacientes que se encontraban en progresión de la enfermedad y los que recibían tratamiento con quimioterapia presentaron mayor probabilidad de morir.

Introduction: the World Health Organization declared COVID-19 as a pandemic on March 11, 2020. A history of cancer is considered a mortality risk factor for multiple diseases; the evolution in patients with neoplastic diseases can be influenced due to superadded conditions such as the case of COVID-19. Objective: to characterize, from a clinical point of view, cancer patients admitted with COVID-19. Methods: a descriptive and cross-sectional research was carried out in cancer patients admitted with COVID-19 at "Dr. Celestino Hernández Robau" University Hospital in Villa Clara from January to December 2021. A number of 78 cancer patients with 5 years or less of evolution was included in the study. Results: male gender and those over 60 years of age predominated. The 39.7% of the patients had lung or laryngeal cancer followed by breast, hemolymphopoietic and colorectal cancers. The 46.2% were in a stable state and 29.5% in palliative care. The 34.6% of them were receiving chemotherapy treatment at the time of admission. Steroids (85.9%), alpha interferon (73.1%) and sodium heparin (55.1%) were the most used drugs. Conclusions: lung and laryngeal tumours were the most common malignancy in cancer patients hospitalized with COVID-19, although breast, prostate, and colorectal tumours, in that order, were associated with higher mortality. Patients with disease progression and those receiving chemotherapy were more likely to die.

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice / 南方医科大学学报

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

High expression of MYH9 inhibits apoptosis of non-small cell lung cancer cells through activating the AKT/c-Myc pathway / 南方医科大学学报

OBJECTIVE@#To investigate the role of myosin heavy chain 9 (MYH9) in regulation of cell proliferation, apoptosis, and cisplatin sensitivity of non-small cell lung cancer (NSCLC).@*METHODS@#Six NSCLC cell lines (A549, H1299, H1975, SPCA1, H322, and H460) and a normal bronchial epithelial cell line (16HBE) were examined for MYH9 expression using Western blotting. Immunohistochemical staining was used to detect MYH9 expression in a tissue microarray containing 49 NSCLC and 43 adjacent tissue specimens. MYH9 knockout cell models were established in H1299 and H1975 cells using CRISPR/Cas9 technology, and the changes in cell proliferation cell were assessed using cell counting kit-8 (CCK8) and clone formation assays; Western blotting and flow cytometry were used to detect apoptosis of the cell models, and cisplatin sensitivity of the cells was evaluated using IC50 assay. The growth of tumor xenografts derived from NSCLC with or without MYH9 knockout was observed in nude mice.@*RESULTS@#MYH9 expression was significantly upregulated in NSCLC (P < 0.001), and the patients with high MYH9 expression had a significantly shorter survival time (P=0.023). In cultured NSCLC cells, MYH9 knockout obviously inhibited cell proliferation (P < 0.001), promoted cell apoptosis (P < 0.05), and increased their chemosensitivity of cisplatin. In the tumor-bearing mouse models, the NSCLC cells with MYH9 knockout showed a significantly lower growth rate (P < 0.05). Western blotting showed that MYH9 knockout inactivated the AKT/c- Myc axis (P < 0.05) to inhibit the expression of BCL2- like protein 1 (P < 0.05), promoted the expression of BH3- interacting domain death agonist and the apoptosis regulator BAX (P < 0.05), and activated apoptosis-related proteins caspase-3 and caspase-9 (P < 0.05).@*CONCLUSION@#High expression of MYH9 contributes to NSCLC progression by inhibiting cell apoptosis via activating the AKT/c-Myc axis.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Consistency comparison of programmed cell death 1-ligand 1 in different immuno-histochemical staining methods / 北京大学学报(医学版)

OBJECTIVE@#To compare the consistency of programmed cell death 1-ligand 1 (PD-L1, clone E1L3N, 22C3, SP263) in different immunohistochemical staining methods.@*METHODS@#The first step was to select the optimal process: The PD-L1(clone E1L3N) antibody recommended process, self-built process ①, self-built process ② and self-built process ③ were used to perform immunohistochemical staining in 5 cases of tonsil tissue. The quality of all slides was scored by expert pathologists (0-6 points). The process with the highest score was selected. The second step was to compare the consistency between the optimal procedure and the two standard procedures. Thirty-two cases of lung non-small cell carcinoma diagnosed by pathology in Peking University First Hospital in the past two years were randomly selected. The 32 cases were stained in parallel with the SP263 and 22C3 standard procedures, and all stained slides were scored by specialized pathologists for tumor proportion score (TPS). The scoring results were grouped according to < 1%, ≥1% to < 10%, ≥10% to < 50%, and ≥50%. The consistency of PD-L1 detection antibody clone E1L3N and 22C3, E1L3N and SP263 staining results was analyzed.@*RESULTS@#Tonsil stained slides scores (0-6 points) were as follows: The recommended protocol was 5, 5, 5, 5 and 5. The self-built process ① was 5, 6, 6, 5 and 6. The self-built process ② was 4, 4, 4, 4 and 4.The self-built process ③ was 3, 3, 3, 3 and 3. The self-built process ① was the best with the highest score. The TPSs of 32 non small cell lung carcinoma (NSCLC) cases were as follows: Of self-built process ①, 6 cases were lower than 1%, 5 cases were from 1% to 10%, 10 cases were from 10% to 50%, and 11 cases were higher than 50%; of 22C3 standard procedure, 5 cases were lower than 1%, 3 cases were from 1% to 10%, 13 cases were from 10% to 50%, 11 cases were higher than 50%; of SP263 standard procedure, 7 cases were lower than 1%, 4 cases were from 1% to 10%, 11 cases were from 10% to 50%, 10 cases were higher than 50%. The results of the consistency test were as follows: The κ value for self-built process ① and 22C3 standard procedure was 0.736 (P < 0.001), the agreement was good; the κ value for self-built process ① and SP263 standard procedure was 0.914 (P < 0.001), the agreement was very good.@*CONCLUSION@#The immunostaining using PD-L1(E1L3N) with validated self-built staining protocol ① by Ventana Benchmark GX platform can obtain high quality of slides, and the TPSs based on these slides are in good agreement with 22C3 and SP263 standard procedures.

Registros Hospitalares de Câncer: Proposta Metodológica para Correção do Estadiamento de Câncer de Pulmão / Hospital-Based Cancer Registry: Methodological Proposal for Correction of Lung Cancer Staging / Registros Hospitalarios de Cáncer: Propuesta Metodológica para la Corrección de la Estadificación del Cáncer de Pulmón

Introdução: Um grande desafio para a utilização de registros e bases de dados secundárias é a qualidade do registro e o percentual de perdas em variáveis estratégicas e necessárias à plena utilização do banco. Objetivo: Propor um método de correção para a variável de estadiamento no âmbito dos Registros Hospitalares de Câncer (RHC), a fim de aprimorar sua completude e qualidade. Método: Estudo descritivo, abrangendo as Unidades da Federação, utilizando-se como fonte de informação o RHC, de janeiro de 2013 a dezembro de 2019. O câncer de pulmão foi escolhido como caso para a correção do banco, em razão da sua alta taxa de mortalidade no Brasil e no mundo. As análises foram realizadas com o software de análises estatísticas SAS Studio e a base de dados organizada em Excel. Resultados: O total de casos registrados no RHC foi de 86.026, e a variável de interesse, o estadiamento, teve um total de 32,0% de perda. Ao final de todas as etapas de correção, a perda foi de 9,8%, correspondendo a 22,2% de recuperação. Conclusão: A metodologia proposta representa um avanço na correção do banco do RHC, possibilitando a utilização dos dados de base secundária, com melhor representatividade das diferentes Regiões do país, sobre o tratamento de câncer de pulmão, com possibilidade de expansão de seu uso para outras topografias

Introduction: A major challenge to utilize the registries and secondary databases is the quality of the data and the percentage of losses in strategic and necessary variables for better effectiveness of the database. Objective: To propose a correction method for the cancer staging variable of the HospitalBased Cancer Registry (HBCR), to improve its completeness and quality. Method: HBCR-based descriptive analysis covering Brazil's Federation Units from January 2013 to December 2019. Due to its high mortality in Brazil and worldwide, lung cancer was selected as case for database correction. The analyzes were performed with the software SAS Studio for statistical analyzes and the data were organized in Excel. Results: The total number of cases registered at the HBCR was 86,026, and 32% the variable of interest, staging, were missed. At the end of the correction process, the missed data reached 9.8%, corresponding to a recovery of 22.2%. Conclusion: The proposed methodology is an advance for the correction of the HBCR database on the treatment of lung cancer, allowing a more extensive use, with better representativeness of different country regions, and potential utilization in other topographies

Introducción: Un gran desafío para el uso de registros y bases de datos secundarias es la calidad del registro en sí, el porcentaje de pérdidas en variables estratégicas y necesarias para el pleno uso de la base de datos. Objetivo: Proponer un método de corrección de la variable estadificación en el ámbito de los Registros Hospitalarios de Cáncer (RHC), con el fin de mejorar su exhaustividad y calidad. Método: Análisis descriptivo, abarcando las Unidades de la Federación. Se utilizó el RHC como fuente de información, de enero de 2013 a diciembre de 2019. El cáncer de pulmón fue elegido como caso para la corrección de la base de datos, debido a su alta tasa de mortalidad en el Brasil y en el mundo. Los análisis se realizaron con el software de análisis estadístico SAS Studio y los datos se organizaron en Excel. Resultados: El total de casos registrados en el RHC fue de 86.026, y la variable de interés, la estadificación, tuvo una pérdida total del 32,0% Al final de todas las etapas esta fue de 9,8%, es decir el 22,2% de recuperación. Conclusión: La metodología propuesta representa un avance en la corrección del RHC, permitiendo una mejor utilización de la base de datos, con una mejor representatividad de las diferentes regiones del país, sobre el tratamiento del cáncer de pulmón, con la posibilidad de expandir su uso a otras topografías

Metastasis of Pulmonary Carcinoma to the Breast: Case Report / Metástase de Carcinoma Pulmonar para Mama: Relato de Caso / Metástasis de Carcinoma Pulmonar a la Mama: Informe de Caso

Introduction: Pulmonary carcinoma is the most prevalent cancer in the world, followed by breast cancer. It has high mortality rates in men and women mainly due to its ability to metastasize. Metastases from lung carcinoma to the breast are extremely rare. The first case described occurred in 1965 and since then there are few cases of this condition reported in the world medical literature. Case report: A 59-year-old woman who complained of low back pain in May 2017. The investigation revealed a metastatic site in the fifth vertebra of the lumbar spine with unknown origin. Six months later, a new lesion was found in the ninth vertebra of the thoracic spine. Immunohistochemistry showed positivity for cytokeratin 7 and TTF1 markers, confirming the hypothesis of lung carcinoma as the primary site. In March 2018, the patient evolved with a symptomatic nodule in the right breast on ultrasound and with positivity for TTF1 on immunohistochemical study, confirming the metastasis of lung carcinoma to the breast. Treated for two years until March 2020, when she presented multiple brain metastases. Patient had no therapeutic success and died. Conclusion: The difficulty in diagnosing lung carcinoma metastasis to the breast stands out, surgeons, clinicians and pathologists should consider this diagnosis, although rare.

Introdução: O carcinoma pulmonar é o câncer mais prevalente no mundo, seguido pelo de mama. Apresenta altas taxas de mortalidade em homens e mulheres, principalmente em virtude da sua capacidade de metastatizar. As metástases do carcinoma de pulmão para a mama são extremamente raras. O primeiro caso descrito ocorreu em 1965 e, desde então, há poucos casos dessa condição relatados na literatura médica mundial. Relato do caso: Mulher, 59 anos, apresentou dor lombar em maio de 2017. A investigação revelou um local metastático na quinta vértebra da coluna lombar sem descobrir sua origem. Seis meses depois, uma nova lesão foi encontrada na nona vértebra da coluna torácica. A imuno-histoquímica mostrou positividade para os marcadores citoqueratina 7 e TTF1, confirmando a hipótese de carcinoma de pulmão como sítio primário. Em março de 2018, a paciente evoluiu com um nódulo sintomático na mama direita ao ultrassom e com positividade para TTF1 no estudo imuno-histoquímico, confirmando tratar-se de metástase de carcinoma de pulmão para a mama. Foi tratada por dois anos até março de 2020, quando apresentou múltiplas metástases cerebrais. A paciente não teve sucesso terapêutico e faleceu. Conclusão: Ressalta-se a dificuldade no diagnóstico de metástase de carcinoma de pulmão para a mama e alertar clínicos, cirurgiões e patologistas para que considerem esse diagnóstico, embora raro.

Introducción: Carcinoma de pulmón es el cáncer más prevalente del mundo, seguido del cáncer de mama. Presenta elevadas tasas de mortalidad en hombres y mujeres, debido principalmente a su capacidad de metástasis. Las metástasis del carcinoma de pulmón hacia la mama son extremadamente raras. El primer caso descrito fue en 1965 y, desde entonces, existen pocos casos de esta afección en la literatura médica de todo el mundo. Informe del caso: Mujer, 59 años, comenzó a experimentar dolor lumbar en mayo de 2017. La investigación reveló un foco metastásico en la quinta vértebra de la columna lumbar sin descubrir su origen. Seis meses después, se encontró una nueva lesión en la novena vértebra de la columna torácica. Inmunohistoquímica mostró positividad para los marcadores citoqueratina 7 y TTF1, confirmando la hipótesis de carcinoma de pulmón como localización primaria. En marzo de 2018, la paciente evolucionó con un nódulo sintomático en la mama derecha en la ecografía y con positividad para TTF1 en el estudio inmunohistoquímico, confirmando que se trataba de una metástasis de carcinoma pulmonar a la mama. Tratada durante dos años hasta marzo de 2020, cuando presentó múltiples metástasis cerebrales. La paciente no tuvo éxito terapéutico y falleció. Conclusión: Destacan la dificultad en el diagnóstico de metástasis de carcinoma pulmonar a la mama y alertar clínicos, cirujanos y patólogos para que consideren este diagnóstico, aunque poco frecuente.

Tumor Rabdomioblástico Inflamatório Pulmonar: Relato de Caso / Pulmonary Inflammatory Rhabdomyoblastic Tumor: Case Report / Tumor Rabdomioblástico Inflamatorio Pulmonar: Informe de Caso

Introdução: Os sarcomas primários do pulmão são tumores malignos raros com incidência estimada em torno de 0,5% de todas as neoplasias pulmonares. De suas tipificações descritas na literatura, duas especialmente, os leiomiossarcomas e os rabdomiossarcomas, apresentam semelhanças em seu perfil genético, morfológico e imuno-histoquímico, o que os levou a receberem uma mesma classificação: tumor rabdomioblástico inflamatório. Esse tipo de tumor costuma acometer tecidos moles em extremidades e tronco, e predomina em meio a homens jovens e de meia-idade. Em razão do pequeno número de casos de tumores rabdomioblásticos relatados na literatura, tanto seu diagnóstico quanto seu tratamento são pouco descritos. Relato de caso: Paciente, sexo feminino, 19 anos, apresentou três episódios de infecção respiratória no lobo inferior do pulmão direito em um período de 18 meses. A tomografia computadorizada do tórax evidenciou obstrução do brônquio intermediário e áreas de bronquiectasias no lobo inferior direito. Diante disso, realizou-se bilobectomia inferior-média, conduzida por cirurgia robótica. A paciente recebeu alta hospitalar três dias depois do pós-operatório. A imuno-histoquímica revelou tumor rabdomioblástico inflamatório de baixo grau. Conclusão: Este relato apresentou um caso de tumor pulmonar raro, abordado por uma técnica cirúrgica ainda não relatada para esse tipo de patologia.

Introduction: Primary lung sarcomas are rare malignant tumors with an estimated incidence of around 0.5% of all lung neoplasms. Of their typifications described in the literature, two especially, leiomyosarcomas and rhabdomyosarcomas, have similarities in their genetic, morphological and immunohistochemical profile, which led them to be classified with the same name: inflammatory rhabdomyoblastic tumor. This type of tumor usually affects soft tissues in the extremities and trunk, and predominates among young and middle-aged men. Due to the small number of cases of rhabdomyoblastic tumors reported in the literature, both their diagnosis and treatment are poorly described. Case report: Female patient, 19 years old, who had three episodes of respiratory infection in the lower lobe of the right lung in a period of 18 months. Computed tomography of the chest showed obstruction of the intermediate bronchus and areas of bronchiectasis in the right lower lobe. In view of this, a lower middle bilobectomy was performed through robotic surgery. The patient was discharged from hospital three days after the operation. Immunohistochemistry revealed low-grade inflammatory rhabdomyoblastic tumor. Conclusion: This report described a case of a rare lung tumor, submitted to a surgical technique not yet reported for this type of pathology.

Introducción: Los sarcomas pulmonares primarios son tumores malignos raros con una incidencia estimada en torno al 0,5% de todas las neoplasias pulmonares. De sus tipificaciones descritas en la literatura, dos en especial, los leiomiosarcomas y los rabdomiosarcomas presentan similitudes en su perfil genético, morfológico e inmunohistoquímico, lo que los llevó a recibir la misma clasificación: tumor rabdomioblástico inflamatorio. Este tipo de tumor suele afectar a los tejidos blandos de las extremidades y el tronco, y predomina en hombres jóvenes y de mediana edad. Debido al escaso número de casos de tumores rabdomioblásticos reportados en la literatura, tanto su diagnóstico como su tratamiento están pobremente descritos. Informe del caso: Paciente de sexo femenino, 19 años que consultó por tres episodios de infección respiratoria en el lóbulo inferior del pulmón derecho en un período de 18 meses. La tomografía computarizada de tórax mostró obstrucción del bronquio intermedio y áreas de bronquiectasias en el lóbulo inferior derecho. Ante esto, se realizó una bilobectomía media baja mediante cirugía robótica. La paciente recibió el alta hospitalaria tres días después de la operación. Se realizó inmunohistoquímica y se definió el diagnóstico de tumor rabdomioblástico inflamatorio de bajo grado. Conclusión: Este informe presenta un caso de tumor pulmonar raro, tratado mediante una técnica quirúrgica aún no reportada para este tipo de patología.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer / 中华肿瘤杂志

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

A brief history of the evolution of lung cancer operation / 中华肿瘤杂志

Surgical operation is one of the significant parts of the comprehensive therapeutic methods of lung cancer. In the history of the development of lung cancer operation, scholars and predecessors at home and abroad have gradually established the current status of lung cancer operation and the framework of comprehensive treatment after continuous understanding of local anatomy of lung, continuous innovation of surgical equipment and continuous reform of surgical methods. In the continuous development and improvement of lung cancer surgical diagnosis and treatment procedures, a set of standardized diagnosis and treatment process of lung cancer screening, early diagnosis and treatment, standardized surgery process, rapid perioperative recovery, postoperative adjuvant treatment and follow-up has been formed. The achievements of lung cancer operation are achieved by scholars standing on the shoulders of giants. In the process of pioneering and innovating, we should go back and review the road that our predecessors have taken, and draw energy from it to continue to create new brilliance in lung cancer operation. In this paper, the evolution history of lung cancer surgery is summarized in order to improve the clinician's understanding of the history of lung cancer surgery.

Clinical diagnosis and treatment of multiple pulmonary nodules / 中华肿瘤杂志

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.

Clinical analysis of combined immunotherapy in patients with malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Clinicopathological features and prognostic factors of patients with lung metastasis of stage Ⅰa~Ⅲb cervical cancer / 中华肿瘤杂志

Objective: To investigate the clinicopathological features and prognostic factors of lung metastasis in patients with cervical cancer after treatment. Methods: The clinicopathological data of 191 patients with lung metastasis of stage Ⅰa-Ⅲb cervical cancer (FIGO 2009 stage) treated in Sichuan Cancer Hospital from January 2007 to December 2020 were analyzed retrospectively. Kaplan Meier method and Log rank test were used for survival analysis, and Cox regression model was used for prognostic factors analysis. Results: Among 191 patients with lung metastasis of cervical cancer, pulmonary metastasis was found in 134 patients (70.2%) during follow-up examination, and 57 patients (29.8%) had clinical symptoms (cough, chest pain, shortness of breath, hemoptysis, and fever). The time from the initial treatment of cervical cancer to the discovery of lung metastasis was 1-144 months in the whole group, with a median time of 19 months. Univariate analysis of the prognosis of lung metastasis after treatment of cervical cancer showed that the diameter of cervical tumor, lymph node metastasis, positive surgical margin, disease-free interval after treatment of cervical cancer, whether it is accompanied by other metastasis, the number, location and maximum diameter of lung metastasis, and the treatment method after lung metastasis are related to the prognosis of patients with lung metastasis of cervical cancer. Multivariate analysis showed that the number of lung metastases and other site metastases in addition to lung metastases were independent factors affecting the prognosis of patients with lung metastases of cervical cancer (P<0.05). Conclusions: For patients with cervical cancer, attention should be paid to chest CT examination during follow-up to guard against the possibility of lung metastasis after treatment. Besides lung metastasis, other site metastasis and the number of lung metastasis are independent factors affecting the prognosis of patients with lung metastasis of cervical cancer. For patients with lung metastasis after treatment of cervical cancer, surgical treatment is an effective treatment. It is necessary to strictly grasp the surgical indications, and some patients can achieve long-term survival. For patients with lung metastasis of cervical cancer who are not suitable for resection of lung metastasis, the remedial treatment of chemotherapy with or without radiotherapy is still a recommended choice.