Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.

Caracterización del uso inapropiado de antibióticos en faringoamigdalitis según los criterios de McIsaac / Characterization of inappropiate use of antibiotics on pharyngoamygdalitis according to McIsaac's criteria / Caracterização do uso indevido de antibióticos em faringotonsilite de acordo com os critérios do McIsaac

Objetivo: Describir el uso irracional de antibióticos en base a criterios de McIsaac (criterios de Centor modificados por McIsaac), en una unidad de salud de primer nivel de atención. Métodos: Se realizó un estudio descriptivo transversal con los registros de pacientes de 3 a 19 años atendidos en el servicio de emergencia (246), con los diagnósticos de faringitis aguda, amigdalitis aguda, e infecciones respiratorias superiores agudas de múltiples sitios y sin especificar. Se estableció como prescripción inadecuada si el facultativo indicó antibióticos con un puntaje menor o igual a 1 sobre 5 puntos o si no prescribió antibióticos con puntaje mayor o 4 sobre 5 puntos. Resultados: Se estimó 24,29% de uso inadecuado de antibióticos de los registros de emergencia. Se prescribió antibióticos en 160 pacientes, de los cuales se encontró que, amoxicilina fue el más utilizado (61,87%); seguido de benzilpenicilina benzatina (28,12%) y en tercer lugar macrólidos (8,12%). Conclusión: En la unidad de primer nivel analizada se encontró que el uso inadecuado de antibióticos es superior a la prevalecía estimada de faringoamigdalitis estreptocócica para el grupo de edad estudiado. Por esto, es imperativo que se tomen las medidas necesarias a nivel institucional y comunitario para lograr su reducción y evitar las complicaciones que se derivan de esta.

Objetivo: Descrever o uso irracional de antibióticos com base nos critérios de McIsaac (critérios de Centor modificados por McIsaac), em uma unidade de saúde de primeiro nível de atenção. Métodos: Foi realizado um estudo descritivo transversal com os prontuários de pacientes de 3 a 19 anos atendidos no serviço de emergência (246), com diagnóstico de faringite aguda, amigdalite aguda, e infecções respiratórias superiores agudas de múltiplos locais e sem especificação. Estabeleceu-se como uma prescrição inadequada se o médico indicou antibióticos com um escore menor ou igual a 1 de 5 pontos ou se ele não prescreveu antibióticos com um escore maior ou igual a 4 de 5 pontos. Resultados: O uso inadequado de antibióticos foi estimado em 24,29% dos prontuários de emergência. Antibióticos foram prescritos em 160 pacientes, dos quais constatou-se que a amoxicilina foi a mais utilizada (61,87%); em segundo, a penicilina benzatina (28,12%); e, em terceiro lugar, os macrolídeos (8,12%). Conclusão: Na unidade de primeiro nível analisada foi encontrado que o uso de antibióticos é superior à prevalência de faringite estreptocócica estimada para a faixa etária estudada. Então, é imperativo que a nível institucional e comunitário sejam tomadas as medidas necessárias para sua redução e evitar as complicações resultantes.

Objective: To describe the irrational use of antibiotics based on McIsaac criteria (Centor criteria modified by McIsaac), in a primary care facility. Methods: A cross-sectional descriptive study was conducted with the medical record of patients from 3 to 19 years old, treated in the emergency department (246), with the diagnoses of acute pharyngitis, acute tonsillitis, and acute upper respiratory infections from multiple sites and not specified. It was established as an inappropriate prescription if the physician indicated antibiotics with a score less than or equal to 1 out of 5 points or if he did not prescribe antibiotics with a score greater than or equal to 4 out of 5 points. Results: Inadequate use of antibiotics was found in 24.29% of emergency records. Antibiotics were prescribed in 160 patients, of which, amoxicillin was the most used (61.87%); followed by benzathine penicillin (28.12%) and in third place macrolides (8.12%). Conclusion: In the first level unit analyzed, it was found that the inappropriate use of antibiotics is superior to the estimated prevalence of streptococcal pharyngitis for the age group studied. Therefore, it is imperative that the necessary measures are taken at the institutional and community level to achieve its reduction and avoid the complications that result from it.

Predictive factors for 6 vs 12 cycles of Folfiri-Bevacizumab in metastatic colorectal cancer.

Early switching to de-intensified maintenance regimen is still a matter of debate in metastatic colorectal cancer (mCRC). The MARTHA trial, a S.I.C.O.G. phase III randomized trial, compared FOLOFIRI+bevacizumab (B) for 12 cycles (6 months) followed by B for up to 12 months (FOLFIRI +B*12 arm) vs FOLFIRI+B for 6 cycles (3 months) followed by capecitabine+B for 4 cycles followed by B for up to 12 months (FOLFIRI+B*6 arm). Chemotherapy-naïve mCRC patients were randomized, primary endpoint was progression free survival (PFS), with overall survival (OS) as a secondary endpoint. A novel analysis, the Death Pace Analysis (DPA), was performed to identify patients who benefited from a specific treatment. No PFS difference was seen in 198 enrolled patients (101 in FOLFIRI+B*12, 97 in FOLFIRI+B*6). A non-significant superior OS was observed for FOLFIRI+B*6 (HR 0.74, p 0.098). The DPA demonstrated that 14% of patients were identifiable as FOLFIRI+B*6-benefiting patients. According to a logistic regression analysis including 23 clinicopathological variables, baseline Hb was the only independent predictor of DPA-defined FOLFIRI+B*6-benefit status. Among patients with Hb ≤ 11.1 gr/dL a statistically significant prolonged OS was observed for FOLFIRI+B*6 over FOLFIRI+B*12 (median OS: 20.7 vs 12.6 months, respectively, HR 0.54, p 0.048). No survival difference was observed between arms in patients with Hb > 11.1. mCRC patients with low baseline Hb levels are better treated with FOLFIRI+B*6 first-line strategy. Possible biological explanations for this finding are being investigated.

Efficacy and tolerability of biweekly bevacizumab, irinotecan, folinic acid and fluorouracil intravenous bolus (BIFF Regimen) in patients with metastatic colorectal cancer: the southern Italy cooperative oncology group experience.

BACKGROUND: We have extensively assessed a biweekly regimen of irinotecan plus folinic acid and fluorouracil bolus (IRIFAFU) in metastatic colorectal cancer (MCRC). Here, we report on the safety and activity of BIFF (bevacizumab plus IRIFAFU) regimen in 94 mCRC patients. PATIENTS AND METHODS: Bevacizumab 5 mg/kg (1 hour), and irinotecan 180 mg/m(2) (1 hour) were given intravenously on day 1, 6S-folinic acid 250 mg/m(2) (2 hours), and fluorouracil 850 mg/m(2) (bolus) were given intravenously on day 2 every 2 weeks for a median of 9 cycles per patient (range, 1-12), and maintenance bevacizumab alone was delivered in 16 cases. RESULTS: Grade ≥ 3 hematologic toxicities were neutropenia (50%) and febrile neutropenia (5%). Most common grade 3 nonhematologic side effects were diarrhea (20%), vomiting (7%), nausea (4%), and stomatitis (4%). Severe hypertension (1%) and epistaxis (1%) rarely occurred. Six complete responses and 44 partial responses were registered, giving a response rate of 53% (95% CI, 43%-64%). Median progression-free survival was 11.5 months (95% CI, 9.0-14.0 months). Forty-three (46%) patients eventually died, and the median overall survival was 24.0 months (95% CI, 20.2-27.8 months). CONCLUSION: Bevacizumab appeared to increase the activity of the IRIFAFU regimen without worsening its tolerability. Efficacy of BIFF was comparable with that reported with other bevacizumab plus irinotecan-based combinations.

Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401.

PURPOSE: Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients. METHODS: A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1, capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU). RESULTS: Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, P = 0.883). CONCLUSIONS: OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.