Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable / Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma

Introducción: En 2007 se consensuó un protocolo asistencial entre los tres centros de trasplante hepático (TH) de Cataluña, que contemplaba el trasplante hepático (TH) asociado a quimiorradioterapia neoadyuvante como tratamiento del colangiocarcinoma perihiliar (CCAp) irresecable. Objetivo: Analizar la aplicabilidad del TH en los pacientes con CCAp incluidos en el protocolo y la supervivencia por intención de tratamiento. Métodos: Estudio observacional multicéntrico que incluye a pacientes de edad ≤ 68 años, diagnosticados de CCAp ≤3 cm (diámetro radial), irresecable, sin afectación ganglionar o metástasis a distancia. Los pacientes recibieron tratamiento neoadyuvante basado en radioterapia externa en una dosis total de 45 Gy, asociado con bolos de 5-fluoracilo durante los tres primeros días de irradiación y posteriormente capecitabina oral. Aquellos en los que no se objetivó signos de progresión se incluyeron en la lista de espera para TH. Resultados: Entre 2007 y 2018, 13 pacientes fueron incluidos en dicho protocolo. Ocho de los 13 pacientes (61%) fueron trasplantados tras un tiempo en lista de espera de 122 días (rango 5-192). La supervivencia por intención de tratamiento a 1 y 5 años fue del 69 y 39%. La supervivencia global post-TH a 1 y 5 años fue del 87 y 62%, con una probabilidad de recidiva del 29% a los cinco años post-TH. Conclusión: La aplicabilidad del trasplante hepático combinado con quimiorradioterapia neoadyuvante ha sido del 61% en nuestra serie y debe ser considerado como un tratamiento potencialmente curativo para pacientes seleccionados con CCAp irresecable y sin enfermedad metastásica. (AU)

Background: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). Aim: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. Methods: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. Results: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. Conclusion: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA. (AU)

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

Management and supportive treatment of frail patients with metastatic pancreatic cancer.

Data regarding management of frail patients with pancreatic ductal adenocarcinoma practice is currently very scarce. Randomized clinical trials usually exclude these subgroup of patients and the majority of the publications only consider chronological age and ECOG performance status for their classification. Therefore, the current available data do not reflect daily clinical practice. Only data from a phase two study (FRAGANCE study), designed to select a tolerable dose-schedule of nab-placitaxel + gemcitabine (Phase one) and to evaluate the efficacy of the selected regimen (Phase two) in patients with ECOG-2 and previously untreated advanced PDAC, are currently available. Management of these particular patients is exceedingly complex and requires collaboration of multidisciplinary teams and intensive support treatment. This article reviews the literature available regarding the management of the so-called frail patients and provide guidance for chemotherapy as well as supportive care treatments.

Supportive care in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with poorest prognosis and represents the third leading cause of cancer-related deaths in Western countries. Despite advances in diagnostic procedures and treatment, diagnosis is made in most cases when the disease is locally advanced or metastatic. Supportive care aims to improve symptoms, reduce hospital admission rates, and preserve quality of life. Proper symptomatic management is critical to allow administration of chemotherapy and radiotherapy. Symptomatic management should be accomplished in a multidisciplinary fashion. Its primary aims include relief of biliary or duodenal obstruction, prevention and/or treatment of thromboembolic disease, and control cancer-related pain. Nutritional support and optimal replacement therapy in patients with endocrine and/or exocrine insufficiency, is mandatory. This manuscript highlights the most significant problems faced when caring for patients with advanced PDAC and provides an evidence-based approach to symptomatic management (AU)

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Supportive care in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with poorest prognosis and represents the third leading cause of cancer-related deaths in Western countries. Despite advances in diagnostic procedures and treatment, diagnosis is made in most cases when the disease is locally advanced or metastatic. Supportive care aims to improve symptoms, reduce hospital admission rates, and preserve quality of life. Proper symptomatic management is critical to allow administration of chemotherapy and radiotherapy. Symptomatic management should be accomplished in a multidisciplinary fashion. Its primary aims include relief of biliary or duodenal obstruction, prevention and/or treatment of thromboembolic disease, and control cancer-related pain. Nutritional support and optimal replacement therapy in patients with endocrine and/or exocrine insufficiency, is mandatory. This manuscript highlights the most significant problems faced when caring for patients with advanced PDAC and provides an evidence-based approach to symptomatic management.

What treatment in 2017 for inoperable pancreatic cancers?

Pancreatic adenocarcinoma is a frequent and severe disease, either diagnosed as metastatic pancreatic adenocarcinoma (MPA) or as locally advanced pancreatic carcinoma (LAPC). Though no improvement in patients outcome have been made between 1996 and 2011, since 5 years new treatment options have become available to treat our patients. New standard first line regimens, such as FOLFIRINOX and gemcitabine combined with nab-paclitaxel, have improved overall survivals and second line treatments have been tested and validated. Other first-line treatments have failed, but research remains active and trials are ongoing with promising new anti-cancer agents. These new effective regimens used for MPA have yielded promising results in LAPC patients in open cohorts or phase II trials and a recent trial have failed to demonstrate the added value of classical external radiotherapy in this setting. Here, we review current standards of care in LAPC and MPA, consider the latest challenges and strategic questions, and examine what we may hope for in the future.

Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain.

The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.

SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)

Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future (AU)

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SEOM Clinical Guideline for the treatment of pancreatic cancer (2016).

Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.

Biliary tract cancers: SEOM clinical guidelines

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease (AU)

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Biliary tract cancers: SEOM clinical guidelines.

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease.

TTD consensus document on the diagnosis and management of exocrine pancreatic cancer

Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management (AU)

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TTD consensus document on the diagnosis and management of exocrine pancreatic cancer.

Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management.

Clinicopathological risk factors of Stage II colon cancer: results of a prospective study.

AIM: Adjuvant 5-fluorouracil based chemotherapy has demonstrated benefit in Stage III colon cancer but still remains controversial in Stage II. The aim of this study was to analyse the prognostic impact of clinicopathological factors that may help guide treatment decisions in Stage II colon cancer. METHOD: Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge and its referral comprehensive cancer centre Institut Català d'Oncologia/L'Hospitalet were prospectively included in a database. We identified 432 patients with Stage II colon cancer operated on at Hospital Universitari Bellvitge. The 5-year relapse-free survival (RFS) and colon-cancer-specific survival (CCSS) were determined. RESULTS: The 5-year RFS and CCSS were 83% and 88%, respectively. Lymphovascular or perineural invasion was associated with RFS [hazard ratio (HR) 1.84; 95% CI 1.01-3.35]. Gender (women, HR 0.48; 95% CI 0.23-1) and lymphovascular or perineural invasion (HR 3.51; 95% CI 1.86-6.64) together with pT4 (HR 2.79; 95% CI 1.44-5.41) influenced CCSS. In multivariate analysis pT4 and lymphovascular or perineural invasion remained significantly associated with CCSS. We performed a risk index with these factors with prognostic impact. Patients with pT4 tumours and lymphovascular or perineural invasion had a 5-year CCSS of 61%vs the 93% (HR 5.87; 95 CI 2.46-13.97) of those without any of these factors. CONCLUSION: pT4 and lymphatic, venous or perineural invasion are confirmed as significant prognostic factors in Stage II colon cancer and should be taken into account in the clinical validation process of new molecular prognostic factors.

The oncology acute toxicity unit (OATU): an outpatient facility for improving the management of chemotherapy toxicity.

OBJECTIVE: To provide an outpatient facility to improve the management of chemotherapy toxicity in cancer patients. PATIENTS AND METHODS: We set up an oncology acute toxicity unit (OATU) to improve toxicity management. A telephone helpline was the initial contact which filters out inappropriate non-toxicity-related events. Patients were provided an information booklet describing the possible side effects of the chemotherapy and the helpline telephone number. A specialist nurse received the calls and consulted the doctor if necessary. Depending on requirements, the patient's problem was resolved by telephone, or a consultation visit at the OATU was arranged. RESULTS: Between February 1999 and August 2001, 1126 patients made 2007 contacts with the OATU. The most common tumours were breast (26%), colorectal (20%) and lung (20%). The telephone helpline was used in 87% of contacts and 37% were considered inappropriate. Of the 1263 appropriate contacts, the most frequent chemotherapy schedules that had been administered were 5FU-leucovorin (11.2%) and CMF (10.4%). The most frequent side effects were fever (35.5%), diarrhoea (18.5%), mucositis (16.2%) and emesis (13%). The problem was resolved by telephone in 48% of cases and 52% required attendance in the OATU, of which 40% required hospital admission, i.e., 21.1% of the initial appropriate helpline contacts. The most frequent reason was Grade 3-4 neutropenic fever (56.5%). CONCLUSIONS: The OATU enables prompt and efficient access of patients to medical oncology facilities in the event of toxicity due to chemotherapy. Unnecessary emergency room use is avoided while oncology outpatient and hospitalisation facilities are optimised.

The oncology acute toxicity unit (OATU): an outpatient facility for improving the management of chemotherapy toxicity

OBJECTIVE: To provide an outpatient facility to improve the management of chemotherapy toxicity in cancer patients. PATIENTS AND METHODS: We set up an oncology acute toxicity unit (OATU) to improve toxicity management. A telephone helpline was the initial contact which filters out inappropriate non-toxicity-related events. Patients were provided an information booklet describing the possible side effects of the chemotherapy and the helpline telephone number. A specialist nurse received the calls and consulted the doctor if necessary. Depending on requirements, the patient's problem was resolved by telephone, or a consultation visit at the OATU was arranged. RESULTS: Between February 1999 and August 2001, 1126 patients made 2007 contacts with the OATU. The most common tumours were breast (26%), colorectal (20%) and lung (20%). The telephone helpline was used in 87% of contacts and 37% were considered inappropriate. Of the 1263 appropriate contacts, the most frequent chemotherapy schedules that had been administered were 5FU-leucovorin (11.2%) and CMF (10.4%). The most frequent side effects were fever (35.5%), diarrhoea (18.5%), mucositis (16.2%) and emesis (13%). The problem was resolved by telephone in 48% of cases and 52% required attendance in the OATU, of which 40% required hospital admission, i.e., 21.1% of the initial appropriate helpline contacts. The most frequent reason was Grade 3-4 neutropenic fever (56.5%). CONCLUSIONS: The OATU enables prompt and efficient access of patients to medical oncology facilities in the event of toxicity due to chemotherapy. Unnecessary emergency room use is avoided while oncology outpatient and hospitalisation facilities are optimised (AU)

Metronomic chemotherapy: an antiangiogenic scheduling.

Conventional cytotoxic anticancer chemotherapeutic drugs were developed with the intent of treating cancer by direct killing or inhibition of growth of cycling tumour cells. Recently, however, there has been considerable interest in the notion of exploiting such drugs as angiogenesis inhibitors. The rationale is based on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells, and endothelial cell division takes place during new blood vessel formation, including tumour angiogenesis. The results of recent experimental studies have suggested that frequent administration of certain cytotoxic agents at low doses, known as "metronomic chemotherapy", increases the putative antiangiogenic activity of certain drugs. Metronomic chemotherapy refers to the chronic administration of comparatively low doses of cytotoxic drugs at close, regular intervals, with no prolonged drug-free interruptions. The advantage of this strategy is lower toxicity and risk of emergence of drug-resistant tumour cells than conventional administration. This review describes the possible antiangiogenesis basis of this therapeutic strategy, the experimental studies published and the recent clinical studies that explore this less toxic schedule.

Metronomic chemotherapy: an antiangiogenic scheduling

Conventional cytotoxic anticancer chemotherapeutic drugs were developed with the intent of treating cancer by direct killing or inhibition of growth of cycling tumour cells. Recently, however, there has been considerable interest in the notion of exploiting such drugs as angiogenesis inhibitors. The rationale is based on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells, and endothelial cell division takes place during new blood vessel formation, including tumour angiogenesis. The results of recent experimental studies have suggested that frequent administration of certain cytotoxic agents at low doses, known as "metronomic chemotherapy", increases the putative antiangiogenic activity of certain drugs. Metronomic chemotherapy refers to the chronic administration of comparatively low doses of cytotoxic drugs at close, regular intervals, with no prolonged drug-free interruptions. The advantage of this strategy is lower toxicity and risk of emergence of drug-resistant tumour cells than conventional administration. This review describes the possible antiangiogenesis basis of this therapeutic strategy, the experimental studies published and the recent clinical studies that explore this less toxic schedule (AU)

Metástasis muscular como primera manifestación de un carcinoma de células renales: presentación de un caso clínico / Renal cell carcinoma presenting as skeletal muscle mass: a case report

Propósito: Descripción de un caso de metástasis muscular como primera manifestación de un Carcinoma de Células Renales (CCR).Material y métodos: Presentamos el caso de una paciente afectada de metástasis muscular de un carcinoma de células renales, la actitud diagnóstica, valoración terapéutica y evolución. Resultados: Se analizan las peculiaridades de la evolución y tratamiento del CCR metastásico. En nuestro caso se inició un tratamiento de combinación con Interferón alfa-2b e Interleukina-2 recombinate (IFN+ IL-2r) que no pudo evitar la rápida progresión de la enfermedad y la muerte de la paciente a los 5 meses del diagnóstico. Conclusiones: La elección del tratamiento en pacientes con CCR metastásico debe ser individualizada en función de los datos obtenidos en el estudio de extensión y de la valoración de los factores pronósticos de la evolución de la enfermedad (AU)