Improving access to high-cost cancer drugs in Latin America: Much to be done.

Lack of access to high-cost medications is a complex issue at the intersection of economics, medicine, politics, and ethics, and it poses a significant threat to global health care. The problem is even more significant in low- and middle-income countries, such as those in Latin America, where governments and individuals struggle to pay for products that are priced at several times the level of their per capita gross domestic product. In this review, we examine the determinants for increasing drug costs and how Latin American countries face this burgeoning crisis. We emphasize that a number of opportunities and strategies to reduce costs and improve access exist and should be identified and implemented, ideally within a regional approach with multiple stakeholders involved and based on systematic and transparent cost-effectiveness analyses. Cancer 2017;123:1313-1323. © 2016 American Cancer Society.

Patterns of care, predictors and outcomes of chemotherapy for ovarian carcinosarcoma: A National Cancer Database analysis.

OBJECTIVE: The aim of this study is to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from those of women with high-grade papillary serous ovarian carcinoma (HG-PSOC) when compared by stage and treatment modalities. METHODS: The National Cancer Database was queried to identify patients with OCS and HG-PSOC diagnosed between 2003 and 2011. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: The final study group consisted of 45,153 women. 2886 (6.39%) had OCS and 42,267 (93.61%) had HG-PSOC. The mean age at diagnosis was 65.43 (±12.21) years for women with OCS and 61.52 (±12.6) years for HG-PSOC (P<0.001). African-American women had higher rate of OCS relative to white non-hispanic women (7.84% vs. 6.37%; P=0.002). Overall, women with OCS had a worse five-year survival rate, 26.63% [95% Confidence Interval (CI)=24.86%-28.53%] vs. 43.61% (95% CI=43.07%-44.17%). This difference persisted for each FIGO disease stage I-IV, with five-year survival consistently worse for women with OCS compared to those with HG-PSOC. Over the entire study period and after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, and lymph node dissection, carcinosarcoma histology was associated with decreased survival. CONCLUSION: OCS is associated with a poor prognosis compared to HG-PSOC. This difference was noted across all FIGO stages.

Colombian consensus for the molecular diagnosis of endometrial cancer / Consenso colombiano para el diagnóstico molecular del cáncer de endometrio.

Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and nonregulatory document.

Objetivos: el programa Cancer Genome Atlas Research (TCGA) desarrolló la clasificación molecular para cáncer endometrial con utilidad pronóstica y terapéutica, la cual ha sido reemplazada por consensos y guías internacionales por la clasificación ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) debido a su alto costo. El objetivo de este artículo es presentar recomendaciones a nivel nacional derivadas de un consenso de expertos que permitan unificar e implementar la clasificación molecular para mujeres con cáncer endometrial, mediante un uso racional de recursos y tecnología. Materiales y métodos: consenso de 36 expertos en oncología clínica, ginecología oncológica, patología y genética con práctica clínica en el territorio nacional. El grupo líder realizó una revisión de la literatura y estructuración de preguntas calificadas de 1 a 9 puntos. Se utilizó la técnica de grupo nominal modificada. Se efectuaron reuniones presenciales con presentaciones magistrales, diálogo deliberativo y votación de cuestionario Google Forms (Google LLC, Mountain View, CA, USA) con análisis y discusión de respuestas. Las respuestas no consensuadas se llevaron a una segunda ronda de votación. Finalmente, se elaboró y revisó el manuscrito final. Resultados: se formularon siete recomendaciones integrando las respuestas de las panelistas basadas en evidencia, pero ajustadas al contexto y a la realidad colombiana. Recomendación 1. Se recomienda realizar la clasificación molecular en todos los carcinomas endometriales utilizando los marcadores de inmunohistoquímica como resultados subrogados del perfil molecular inicialmente propuesto en la clasificación del TCGA. Recomendación 2. Se recomienda la estrategia secuencial de testeo iniciando por los marcadores de inmunohistoquímica (p53, MLH1, MSH 2, MSH6, PMS2) simultáneamente en todas las pacientes, y definir la solicitud del POLE (polimerasa épsilon del DNA) (si se encuentra disponible) de forma diferida de acuerdo con la clasificación de riesgo basado en la pieza quirúrgica. Recomendación 3. Se recomienda que sea el ginecólogo oncólogo quien solicite el POLE (si se encuentra disponible) de acuerdo con el reporte de patología definitivo. Esta prueba se debe solicitar a todos los cánceres endometriales de estadio I-II, excepto los de bajo riesgo (estadio IA endometrioide de bajo grado sin invasión linfovascular p53 normal) y estadio III-IV sin enfermedad residual, sin afectar la solicitud de los marcadores moleculares subrogados por inmunohistoquímica de acuerdo con la histología. El consenso propone que la solicitud del POLE se realice posterior a la inmunohistoquímica y de acuerdo con la clasificación del riesgo según las categorías establecidas por la guía ESGO/ESTRO/ESP del 2020. Recomendación 4. Se recomienda realizar simultáneamente con los otros marcadores de inmunohistoquímica la prueba para receptores hormonales en todas las pacientes con cáncer endometrial y el HER2 en pacientes con p53abn. Recomendación 5. Se recomienda que los marcadores de inmunohistoquímica (p53, MLH1, MSH2, MSH6 y PMS2) se realicen en la biopsia/legrado endometrial inicial cuando la muestra es adecuada y está disponible. En caso de inmunohistoquímica inicial no concluyente, o discrepancias histológicas entre la patología inicial y definitiva, se recomienda repetir el perfil molecular en la patología quirúrgica. Los marcadores de inmunohistoquímica deben reportarse en el informe de patología de acuerdo con las recomendaciones del CAP (College of American Pathologists), independientemente del tipo de muestra. Recomendación 6. Se recomienda realizar estudio de metilación de promotor de MLH1 en pacientes con pérdida de expresión de MLH1 en la inmunohistoquímica, acompañado o no de pérdida de expresión de PMS2. Todas las pacientes con déficit de MMR (mismatch repair), deben ser enviadas a genética para descartar síndrome de Lynch. Recomendación 7. Se recomienda tener en cuenta la clasificación molecular, además de los criterios histopatológicos clásicos para la toma de decisiones de adyuvancia, tal como los incorpora la clasificación de los grupos pronósticos de la guía ESGO/ ESTRO/ESP del 2020. Conclusiones: es necesario implementar la clasificación molecular de cáncer de endometrio en la práctica clínica acorde al contexto colombiano, dado su valor pronóstico y posiblemente predictivo. Esto permitirá la caracterización de la población colombiana para ofrecer tratamientos guiados de manera individualizada. Se trata de un documento académico y no regulatorio.

Metastatic Pancreatic Cancer: Where Are We?

Pancreatic cancer is one of the most lethal neoplasms worldwide; it is aggressive in nature and has a poor prognosis. The overall survival rate for pancreatic cancer is low. Most patients present non-specific symptoms in the advanced stages, which generally leads to late diagnosis, at which point there is no option for curative surgery. The treatment of metastatic pancreatic cancer includes systemic therapy, in some cases radiotherapy, and more recently, molecular targeted therapies, which can positively impact cancer control and improve quality of life. This review provides an overview of the molecular landscape of pancreatic cancer based on the most recent literature, as well as current treatment options for patients with metastatic pancreatic cancer.

Painful shoulder and scapula as initial presentation of advanced lung adenocarcinoma.

Lung adenocarcinoma is a common cancer; even though it has a strong association with previous smoking, there has been described nonsmokers-related cases. Symptoms varies from asymptomatic to hemoptysis or pleural effusion. We describe a case of a patient who presented with painful scapula as primary manifestation of advanced pulmonary malignancy.

Sexual dysfunction as a challenge in treated breast cancer: in-depth analysis and risk assessment to improve individual outcomes.

The increasing number of breast cancer survivors has led to a greater emphasis on issues related to quality of life (QoL). Up to 75% of women treated for breast cancer (BC) report sexual disorders. However, most oncologists are not trained to recognize which patients are at high-risk of developing sexual disorders. Female sexual dysfunction (FSD) is common in patients with BC; we found that patients without FSD prior to BC treatment are at risk of developing FSD after treatment. Treatment of early BC relies on the combination of chemotherapy, surgery, and radiation therapy. All these treatments have side effects or sequelae identified as high-risk factors for the development of FSD. The choice of less toxic treatments in each modality could reduce the risk of FSD in some cases, without affecting the risk of recurrence or effectiveness. A comprehensive approach of BC must consider FSD as a determinant factor of QoL in survivors.

Thyroid cancer in women of reproductive age: Key issues for the clinical team.

Women who are fertile experience a significant burden from thyroid cancer. In reality, delaying childbirth is the current trend in maternity. Women who have thyroid cancer may later want to get pregnant after it has been treated, which presents a multidisciplinary issue for their doctors. A variety of specialists are frequently involved in the treatment of thyroid cancer. This review aims to address the key elements of the strategy and places special emphasis on the significance of fertility in women with thyroid cancer diagnosis and remission. We will cover topics including the role of thyroid hormones in pregnancy and fertility.

Endometrial carcinosarcoma: a poor prognosis debut with favourable therapeutic outcome.

Endometrial carcinosarcoma (ECS) is a rare, highly aggressive disease characterised by a biphasic growth of malignant epithelial (carcinomatous) and mesenchymal (sarcomatous) components. Clinically, it cannot be distinguished from endometrial carcinoma or uterine sarcoma. The definitive diagnosis can only be made based on histological examination and immunohistochemistry. To date, there aren't standardised treatment protocols for its management. We report a case of a 73-year-old patient who presented postmenopausal abnormal uterine bleeding and was diagnosed with ECS. A non-conventional treatment approach was conducted with favourable oncological outcomes.

Asbestos and cancer in Latin America and the Caribbean: we may have won some battles, but definitely not the war.

Only six countries have banned the industrial use of asbestos in Latin America and the Caribbean. In fact, the industrial use of asbestos appears to be growing in this region. Asbestos is one of the most dangerous natural substances in the world, it is contained in several types of rocks (such as serpentinites, mafic and ultramafic rocks) but fibers can be released to the atmosphere both by natural and antropogenic sources. Six countries have banned the industrial use of asbestos in this region, we expected that laws established before 2007 would be less adherent to the 2007 WHO/ILO recommendations. In contrast, the Chilean law of 2001 is one of those that most adheres to international recommendations along with the Colombian law of 2021. Which means that the newest laws are not necessarily the strongest. This article aims to draw a regional overview of the laws against asbestos production in Latin America and the Caribbean, highlighting the strengths and weaknesses of each national policy. We recommend that countries that have already banned asbestos consider updating and strengthening their existing laws and develop clinical guidelines for the management, monitoring, and rehabilitation of asbestos-related diseases. The challenge of asbestos goes far beyond a prohibition law.

Current and emerging therapies of HER2-positive metastatic breast cancer.

The HER2 receptor as measured by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is overexpressed in 15-20% of all breast cancers and traditionally represents adverse biology and a guarded prognosis, particularly in HER2 positive metastatic breast cancer (MBC). Trastuzumab and newer anti-HER2 targeting agents have significantly improved the clinical outcomes of patients with HER2 positive MBC. The development of new techniques has led to discovery of promising biomarkers that can lead to more precise selection of patients for anti-HER2 therapies. This paper summarizes these new biomarkers, useful in selecting patients for treatment with new and emerging therapies for HER2 positive MBC. Emerging next generation sequencing techniques have truly changed the landscape of HER2 positive MBC. Deployment of multiple anti-HER2 therapies in combination is a strategy which has yielded additive or even synergistic effects and has led to markedly improved patient outcomes in HER2+ MBC. In the future, in order to further improve the treatment of these patients and to reduce toxicities, we need to improve our understanding of HER2-dependent pathways and their function, and to develop further treatment combinations while optimizing selection of patients by identifying new biomarkers. The results of prospective studies using CTCs, cDNA and other promising new biomarkers are awaited with great interest.