Determining Clinicopathologic Factors That Influence Treatment in Advanced Breast Cancer in Argentina After CDK4/6 Inhibitors.

PURPOSE: The optimal treatment sequence for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated. MATERIALS AND METHODS: This is a retrospective analysis of a real-world cohort including patients with HR+/HER2- ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment. Clinical and biological factors were analyzed to evaluate their association with daily treatment decisions and the prognostic role of progression-free survival (PFS) in the second-line setting. RESULTS: Two hundred thirty-five patients were included. Second-line treatments were hormone therapy (HT) based in 60% and chemotherapy based in 40% of patients. The second-line median PFS was 6.6 months, with no difference between treatment types. In multivariable analysis, postmenopausal status, lower Ki-67 expression, and non-de novo stage IV disease were associated with improved second-line (2L) PFS. Menopausal status significantly interacted with treatment type, with reduced PFS in premenopausal patients receiving HT-based treatments (4.7 v 8.7 months, P = .00045). CONCLUSION: In our study, treatment decisions reflected the current algorithm incorporated in our clinical guidelines, and prior treatment response was the most relevant factor to determine 2L treatment decision. Menopausal status interacted with the subsequent therapy efficacy in this setting. Hence, we consider that menopausal status should be routinely evaluated in the subgroup analysis of clinical trials.

Endometrial cancer treatment and outcomes in Argentina: ECHOS-A real-world study.

Objective: Real-world data for patients with endometrial cancer (EC) are limited, particularly in Latin America. We present treatment pattern findings from ECHOS-A - Endometrial Cancer Health Outcomes Study in Argentina. Materials and methods: A retrospective study using clinical data from privately insured patients with EC diagnosed from 2010 to 2019. Index (diagnosis proxy) was first date of an EC-related health term or treatment. Demographics, clinical characteristics, and FIGO staging were described. Disease progression and survival were assessed until study end, loss to follow-up, or death. Results: Of 805 patients with EC, 77.4 % (n = 623/805) received any treatment and 22.6 % (n = 182/805) received none. Among those treated, 31.8 % (n = 198/623) had first-line (1L) systemic therapy, and 45.5 % (n = 90/198) proceeded to second-line (2L) therapy. Mean follow-up was 33.6 (SD 31.8) months. Of those receiving any treatment, 87.3 % (n = 544/623) had FIGO stage data (I, 62.9 %; II, 18.6 %; III, 13.6 %; IV, 5.0 %). Treatment by class in 1L and 2L, respectively, were platinum chemotherapy, 73.7 %, 36.7 %; non-platinum chemotherapy, 73.7 %, 62.2 %; immunotherapy, 1.0 %, 11.1 %; hormone therapy, 17.7 %, 26.7 %. Carboplatin/paclitaxel was the most frequent 1L (52.5 %) and 2L (14.4 %) regimen. Mean time to progression was 14.1 (SD 16.3) and 8.8 (SD 8.3) months in 1L and 2L, respectively. Adjusted 1- to 5-year risk of progression/death was 46.5-77.5 % and 65.0-86.2 % in 1L and 2L, respectively. Conclusions: Approximately one-quarter of patients with EC received no treatment, and approximately two-thirds were not treated with 1L systemic therapy. Efforts to better understand the reasons for these treatment patterns are crucial for improving patient outcomes.

OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer.Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively.Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n =311 [87.6%]; Brazil: n = 1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line.Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

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[High-risk endometrial carcinoma in early stages: Hospital Italiano de Buenos Aires, oncological results]. / Carcinoma de endometrio de alto riesgo en estadios iniciales: resultados oncológicos, Hospital Italiano de Buenos Aires

Introduction: Endometrial cancer is the second most frequent gynecological tumor in Argentina, representing 6% of all cancers in women. The objective of this study is to evaluate the oncological and perioperative results in patients with high-risk endometrial cancer (HREC) limited to the uterus, treated at the Hospital Italiano de Buenos Aires, between January 2010-2018. Methods: Retrospective cohort study that evaluated perioperative results, disease-free survival at 2, 4 years in patients with HREC. Results: Of a total of 123 patients, 74 met the inclusion criteria. Serous tumors were the most frequent histological type, n=38 (51%), while dedifferentiated tumors were the least frequent, n=2 (3%). Of all the patients included, 56 (76%) received at least one adjuvant treatment. Taxol platinum-based chemotherapy was implemented in 28 patients (38%), while 24 (33%) received a combination of chemotherapy and radiotherapy. The median follow-up time was 2.9 years. Disease-free survival in patients with stage IA at 2 and 4 years was 71% (95% CI 55-82) and 63% (CI 46-76), respectively, while those with stage IB were 53 (95% CI 33-70) and 38 (95% CI 19-58). Regarding the surgical approach, no significant differences were found in disease-free or overall survival when comparing the laparoscopic with the laparotomy approach (p=0.06). Conclusion: Only the FIGO stage showed an increased probability of death or relapse regardless of the type of adjuvant treatment and the type of surgery approach. Perioperative complications were similar in both approaches.

Introducción: En Argentina el cáncer de endometrio es el segundo tumor ginecológico más frecuente, representando el 6% de todos los cánceres en mujeres. El objetivo de este trabajo es evaluar los resultados oncológicos y perioperatorios, en pacientes con cáncer de endometrio de alto riesgo (CEAR) limitados al útero tratadas en el Hospital Italiano de Buenos Aires entre enero 2010-2018. Métodos: Estudio de cohorte retrospectivo que evaluó los resultados perioperatorios, la supervivencia libre de enfermedad a los 2, 4 años en pacientes con CEAR. Resultados: 74 pacientes cumplieron con los criterios de inclusión. Los tumores serosos fueron los más frecuente n=38 (51%), mientras que los desdiferenciados, los de menor frecuencia, n=2 (3%). 56 (76%) pacientes recibieron al menos un tratamiento adyuvante. El tratamiento sistémico fue implementado en 28 pacientes (38%), mientras que 24 (33%) recibieron una combinación de quimioterapia y radioterapia.  La mediana de seguimiento fue de 2,9 años. La supervivencia libre de enfermedad, en pacientes con estadio IA a los 2 y 4 años fue de 71% (IC 95% 55-82) y 63 % (IC 46 -76) respectivamente, mientras que aquellas que presentaban un estadio IB fue de 53 (IC 95% 33-70) y 38 (IC 95% 19-58). En cuanto a la vía quirúrgica de abordaje, no se encontraron diferencias significativas en la supervivencia libre de enfermedad ni en las complicaciones perioperatorias. Conclusión: Sólo el estadio FIGO mostró un aumento en la probabilidad de muerte o recaída independientemente del tipo de tratamiento adyuvante realizado y de la vía de abordaje seleccionada.

Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos / Lynch syndrome: impact of the characterization of families based on genetic studies

El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes) MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p <0.01), que las 27 sin mutaciones. La implementación de estudios genéticos permitió caracterizar variables demográficas en base a la identificación de mutaciones germinales asociadas al síndrome de Lynch, identificándose dos grupos diferenciados por la edad de afectación y la incidencia de tumores extracolónicos (AU)

The aim of this study was to characterize demographically and molecularly families diagnosed with Lynch syndrome based on genetic studies. Families with a genetic study performed between 1996 and 2017 (sequencing and/or determination of large rearrangements of a mismatch repair gene at least) were selected from the prospective database REM-CCR of Hospital Italiano de Buenos Aires (Clinical trials. Gov NCT02781337). Fifty families fulfilled Amsterdam criteria were analyzed. Pathogenic variants were found in 23 out of 50 (46%) families, being 21 pathogenic and 2 likely pathogenic. The 28.6% of the pathogenic variants were originally described in this series. Among them, the variant c.1911del in MSH2 in a family with breast cancer aggregation and a founder MLH1 mutation from Piedmont, Italy (c.2252_2253del) were identified. Affected genes include MSH2 (13 variants), MLH1 (9 variants), PMS2 (1 variant). Mutations detection rates was 46%. Those families with an identified mutation (n=23) had a lower median age of cancer onset (46 vs. 50 years, p=0.02) and a higher incidence of extra-colorectal tumors (90.5% vs. 45.8%, p<0.01) than those without identified mutations (n=27). The implementation of genetic studies allowed characterizing demographic variables based on the identification of germline mutations associated with Lynch syndrome. Two groups, Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos 3 differentiated by the age of cancer onset and the incidence of extracolonic tumors were characterized (AU)

Impacto del Score de Recurrencia de 21 genes en la indicación de tratamiento sistémico adyuvante: nuestra experiencia en el Hospital Italiano de Buenos Aires / Impact of the Recurrence Score on clinical decision-making about chemotherapy in the adjuvant setting: our experience at Hospital Italiano of Buenos Aires (Argentina)

Introducción Las plataformas genómicas han tomado gran relevancia como factores pronósticos y predictivos para definir tratamiento adyuvante en pacientes con cáncer de mama. Su uso permitiría discriminar un subgrupo de pacientes en quienes la indicación de quimioterapia podría ofrecer más morbilidad que verdadero beneficio. Objetivos Describir las características de las pacientes en quienes se utilizó la plataforma Oncotype DX® y evaluar el impacto del Score de Recurrencia (Recurrence Score) como herramienta de decisión para la indicación de adyuvancia. Material y método Se consideraron pacientes operadas entre 2013 y 2017 en el Hospital Italiano de Buenos Aires, Argentina, con diagnóstico de carcinoma invasor primario de mama de subtipo Luminal A o B, her2neu negativas. Se seleccionaron los casos en los que se solicitó Oncotype DX® y se describieron sus características clínicas e histológicas. Resultados Se utilizó Oncotype DX® en 47 pacientes con cáncer de mama invasor. En el 48,9% se obtuvo un Recurrence Score de riesgo bajo, en el 40,4% de riesgo intermedio y en el 10,6% de riesgo alto. En 22 casos (46,8%) consideramos que hubo un cambio de conducta en la indicación de adyuvancia. Conclusiones En nuestra experiencia, hemos visto que la plataforma genómica Oncotype DX® sería una herramienta útil para definir tratamiento adyuvante en tumores de tipo Luminal, her2neu negativo.

Introduction Over the past decade, gene expression assays have become relevant prognostic factors for guiding clinical decision-making in patients with breast cancer. Their use allows to discriminate which patients are most likely to benefit from chemotherapy in the adjuvant setting, avoiding unnecessary toxicity. Objectives To describe the clinical and pathologic characteristics of patients in whom Oncotype DX® was used as a prognostic factor and assess the impact of the Recurrence Score on clinical decision-making. Materials and method Patients who underwent surgery at the Hospital Italiano de Buenos Aires, Argentina, between 2013 and 2017 for Estrogen-Receptor positive (er+), her2neu negative primary breast cancer were considered eligible. We evaluated the cases in which Oncotype DX® was ordered and described the clinical and pathologic characteristics, as well as whether Recurrence Score (rs) modified the prescription of adjuvant therapy. Results Oncotype DX® was performed in 47 patients. The distribution of patients according to rs was as follows: low risk rs 48,9%, intermediate risk 40,4% and high risk 10,6%. We considered that adjuvant therapy decision was modified after rs in 22 patients (46,8%). Conclusions Oncotype DX® and its resulting Recurrence Score appear to be a clinically useful tool for decision-making in the adjuvant setting for patients with er+, her2neu negative breast cancer.

Mastectomías con conservación de piel y reconstrucción inmediata: nuestra experiencia en el Hospital Italiano de Buenos Aires / Skin Sparing Mastectomy and Immediate Reconstruction: Our experience at the Hospital Italiano de Buenos Aires

La indicación de conservación de piel en la cirugía radical ha ido tomando un rol de mayor relevancia, asociado al aumento del número de reconstruccionesinmediatas. Objetivo: El objetivo de este trabajo fue describir las características de la población sometida a reconstrucción mamaria, compararlas con las de las pacientes no reconstruidas y describir los eventos durante el seguimiento (recaída local, a distancia y muerte). Material y método: Estudio retrospectivo de cohorte, que incluye a las pacientes con carcinomainvasor de la mama tratadas con mastectomía, con y sin reconstrucción inmediata, entre los años 2007 y 2013 en el Hospital Italiano de la Ciudad de Buenos Aires. Se evaluaron las características clínicas e histopatológicas. Resultados: En total, entre los años 2007 y 2013 hubo 466 pacientes sometidas a mastectomía, en 131 de las cuales se hizo reconstrucción inmediata. El número de mastectomías con reconstrucción inmediata creció exponencialmente durante los últimos años, aunque no se evidencia un aumento en la tasa global de mastectomía. Ambas poblaciones con y sin reconstrucción inmediataeran comparables en cuanto a la distribución de subtipos intrínsecos, pero hubo mayor edad y proporción de tumores G3 y mayores a 2 cm en las pacientes no reconstruidas. En relación con la sobrevida, observamos que hubo menor proporción de eventos en la población reconstruida. Conclusiones: En los últimos años, en nuestro servicio ha aumentado la indicación de reconstrucción inmediata. La población de pacientes reconstruidas fue más joven y con tumores más pequeños. Aunque aún falta tiempo de seguimiento, parecería ser que la reconstrucción inmediata sería una opción factible y segura en los cánceres de mama en estadios tempranos...