Machine Learning Quantification of Intraepithelial Tumor-Infiltrating Lymphocytes as a Significant Prognostic Factor in High-Grade Serous Ovarian Carcinomas.

The prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) has been demonstrated in various neoplasms. The few publications that have addressed this topic in high-grade serous ovarian carcinoma (HGSOC) have approached TIL quantification from a semiquantitative standpoint. Clinical correlation studies, therefore, need to be conducted based on more accurate TIL quantification. We created a machine learning system based on H&E-stained sections using 76 molecularly and clinically well-characterized advanced HGSOC. This system enabled immune cell classification. These immune parameters were subsequently correlated with overall survival (OS) and progression-free survival (PFI). An intense colonization of the tumor cords by TILs was associated with a better prognosis. Moreover, the multivariate analysis showed that the intraephitelial (ie) TILs concentration was an independent and favorable prognostic factor both for OS (p = 0.02) and PFI (p = 0.001). A synergistic effect between complete surgical cytoreduction and high levels of ieTILs was evidenced, both in terms of OS (p = 0.0005) and PFI (p = 0.0008). We consider that digital analysis with machine learning provided a more accurate TIL quantification in HGSOC. It has been demonstrated that ieTILs quantification in H&E-stained slides is an independent prognostic parameter. It is possible that intraepithelial TIL quantification could help identify candidate patients for immunotherapy.

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8-8.1). The median PFS was 5.3 months (95% CI 3.2-7.3), and OS was 9.7 months (95% CI 7.6-11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0-1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00-€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0-1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

Use of health-care services during chemotherapy for breast cancer.

AIM OF THE STUDY: The authors analyse the effect of chemotherapy on the use of additional health-care resources and report the clinical and demographic factors associated with such use. PATIENTS AND METHODS: In women with breast cancer, eligible to receive first-line (neo)-adjuvant or palliative chemotherapy, consultations with health-care practitioners (general practitioners [GPs] and specialists) and admissions to emergency department and to hospital were prospectively recorded. Differences were studied according to these clinical and demographic variables: age, tumour stage, performance status, weight, height, body mass index, surgery type, chemotherapy type, number of courses, comorbidity, marital status, educational level, social status and occupational status. RESULTS: Among 268 patients, 124 (42.2%) required one or more non-protocol health-care encounters. 180 visits were generated (GP 23.3%, specialist 35.5%, emergency department admission 21.1%, hospital admission 8.3%, others 3.3% and more than one resource 8.3%). Of total consultations 150 (83.3%) were chemotherapy-related. The number of visits was higher in the first courses. Fever and infection were the most frequent reasons for consultation in all resources. The dependent variable: 'need for non-protocol health-care encounter in any course' was statistically associated with age (p=0.002) and marital status (p=0.021); no association was found with other variables. In multivariate analysis, age (p=0.001) and marital status (p=0.009) remained statistically significant. Younger and married patients consumed less extra health resources. CONCLUDING STATEMENT: Many patients receiving chemotherapy consume health-care resources in addition to their routine visits, usually treatment-related. Patients consult less in the later courses. Older and unmarried women in particular need extra care during chemotherapy.

[Evaluation of response to neoadjuvant chemotherapy using breast scintigraphy in breast cancer]. / Utilidad de la gammagrafía mamaria en la valoración de la respuesta a la quimioterapia neoadyuvante en el cáncer de mama.

BACKGROUND AND OBJECTIVE: We sought to evaluate the usefulness of Tc-99m-sestamibi breast scintigraphy in predicting neoadjuvant chemotherapy response in patients with breast cancer. PATIENTS AND METHOD: In 50 consecutive patients with breast cancer stages II and III, physical examination, mammography and scintimammography were performed before and after the administration of neoadjuvant chemotherapy. The 3 assessments were compared for predictive value using a pathological response as reference. Values derived from visual assessment of the scintimammography, a quantitative tumor/background index, and isotope clearance were compared to the immunohistochemical expression of P-glycoprotein, vascular endothelial growth factor (VEGF) and microvessel density (CD31) in relation to neoadjuvant chemotherapy response. RESULTS: Macroscopic response was obtained in 10 cases (20%). Sensitivity was 86.5% (95% confidence interval [CI], 70.4-94.9) for the physical examination, 83.3% (95% CI, 68-92.5) for the mammography and 76.5% (95% CI, 58.4-88.6) for the scintimammography. Specificity was 38.5% (95% CI, 15.1-67.7) for the physical examination, 42.9% (95% CI, 11.8-79.8) for the mammography and 8.3% (95% CI, 0.4-40.2) for the scintimammography. There were no statistically significant differences in isotope uptake and clearance with regard to response nor in relation to levels of expression of P-glycoprotein, VEGF and microvessel density. CONCLUSIONS: Breast scintigraphy with Tc-99m-sestamibi is not useful in predicting the response to neoadjuvant chemotherapy in breast cancer. Traditional physical examination and mammography are more effective. Isotope uptake and clearance do not predict response and there is not an effective in vivo measurement of chemo-resistance or tumor angiogenesis.

Utilidad de la gammagrafía mamaria en la valoración de la respuesta a la quimioterapia neoadyuvante en el cáncer de mama / Evaluation of response to neoadjuvant chemotherapy using breast scintigraphy in breast cancer

Fundamento y objetivo: Se evalúa la utilidad de la gammagrafía mamaria con tecnecio 99m-sestamibi para determinar la respuesta a la quimioterapia neoadyuvante en el cáncer de mama. Pacientes y método: En 50 pacientes consecutivas con carcinoma de mama, estadios II y III, se practicó exploración física, mamografía y gammagrafía mamaria antes y después de la quimioterapia neoadyuvante. Se realizó una comparación ciega entre las 3 pruebas considerando la respuesta patológica el patrón de referencia. Se efectuó un análisis visual de la gammagrafía mamaria y un análisis cuantitativo de índices tumor/fondo tempranos y tardíos y de aclaramiento. Su valor se relacionó con la expresión inmunohistoquímica de glucoproteína P, con el factor de crecimiento vascular endotelial, con la densidad de microvasculatura (CD31) y con la respuesta. Resultados: Se obtuvo respuesta macroscópica en 10 casos (20%). La sensibilidad fue del 86,5% (intervalo de confianza [IC] del 95%, 70,4-94,9) para la exploración física, del 83,3% (IC del 95%, 68-92,5) para la mamografía y del 76,5% (IC del 95%, 58,4-88,6) para la gammagrafía mamaria. La especificidad fue del 38,5% (IC del 95%, 15,1-67,7) para la exploración física, del 42,9% (IC del 95%, 11,8-79,8) para la mamografía y del 8,3% (IC del 95%, 0,4-40,2) para la gammagrafía mamaria. No se han encontrado diferencias en la captación y el aclaramiento de pacientes con o sin respuesta a la quimioterapia ni en aquellas con diferente expresión de glucoproteína P, factor de crecimiento vascular endotelial y diferente densidad de microvasculatura. Conclusiones: La gammagrafía mamaria con tecnecio 99m-sestamibi no es útil en la valoración de la respuesta a la quimioterapia neoadyuvante en el carcinoma de mama. La exploración física y la mamografía la superan en eficacia. La captación y el aclaramiento no son predictivos de la respuesta y no constituyen parámetros de medición in vivo de la quimiorresistencia ni de la angiogenia tumoral

Background and objective: We sought to evaluate the usefulness of Tc-99m-sestamibi breast scintigraphy in predicting neoadjuvant chemotherapy response in patients with breast cancer. Patients and method: In 50 consecutive patients with breast cancer stages II and III, physical examination, mammography and scintimammography were performed before and after the administration of neoadjuvant chemotherapy. The 3 assessments were compared for predictive value using a pathological response as reference. Values derived from visual assessment of the scintimammography, a quantitative tumor/background index, and isotope clearance were compared to the immunohistochemical expression of P-glycoprotein, vascular endothelial growth factor (VEGF) and microvessel density (CD31) in relation to neoadjuvant chemotherapy response. Results: Macroscopic response was obtained in 10 cases (20%). Sensitivity was 86.5% (95% confidence interval [CI], 70.4-94.9) for the physical examination, 83.3% (95% CI, 68-92.5) for the mammography and 76.5% (95% CI, 58.4-88.6) for the scintimammography. Specificity was 38.5% (95% CI, 15.1-67.7) for the physical examination, 42.9% (95% CI, 11.8-79.8) for the mammography and 8.3% (95% CI, 0.4-40.2) for the scintimammography. There were no statistically significant differences in isotope uptake and clearance with regard to response nor in relation to levels of expression of P-glycoprotein, VEGF and microvessel density. Conclusions: Breast scintigraphy with Tc-99m-sestamibi is not useful in predicting the response to neoadjuvant chemotherapy in breast cancer. Traditional physical examination and mammography are more effective. Isotope uptake and clearance do not predict response and there is not an effective in vivo measurement of chemo-resistance or tumor angiogenesis