An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib

Background. Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. Purpose. To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. Materials and methods. Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel’s c-index (HCI) and Akaike criteria (AIC). Results. The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). Conclusions. PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed (AU)

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An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. PURPOSE: To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. MATERIALS AND METHODS: Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). RESULTS: The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). CONCLUSIONS: PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS).

BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.

SEOM Clinical Guideline for the diagnosis and treatment of esophageal cancer (2016).

Esophageal cancer (EC) is an aggressive tumor that represents the 6th most common cause of cancer death worldwide. The estimated incidence in Spain is 2090 cases/year. Two main pathological subtypes exist, squamous cell carcinoma and adenocarcinoma. The main differences between them are localization and underlying factors which are the principal cause of the recent incidence changes observed in west countries. Staging techniques and treatment options which combine surgery, chemotherapy and radiotherapy, reflected the high complexity of the EC management. An undeniably multidisciplinary approach is, therefore, required. In this guide, we review the status of current diagnosis and treatment, define evidence and propose recommendations.

SEOM Clinical Guideline for the diagnosis and treatment of esophageal cancer (2016)

Esophageal cancer (EC) is an aggressive tumor that represents the 6th most common cause of cancer death worldwide. The estimated incidence in Spain is 2090 cases/year. Two main pathological subtypes exist, squamous cell carcinoma and adenocarcinoma. The main differences between them are localization and underlying factors which are the principal cause of the recent incidence changes observed in west countries. Staging techniques and treatment options which combine surgery, chemotherapy and radiotherapy, reflected the high complexity of the EC management. An undeniably multidisciplinary approach is, therefore, required. In this guide, we review the status of current diagnosis and treatment, define evidence and propose recommendations (AU)

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Clinical guideline SEOM: hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications (AU)

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Clinical guideline SEOM: hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications.

Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative chemoradiotherapy in patients with resectable rectal cancer. A single-institution experience

INTRODUCTION: Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance. MATERIAL AND METHODS: Between 1999 and 2009, 126 RC patients with T3-T4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4-6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR). RESULTS: Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3-4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes. CONCLUSIONS: Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear (AU)

Orbital and myocardial metastases of a primary pulmonary melanotic schwannoma

We present the case of a 60-year-old man with a primary pulmonary melanotic schwannoma treated with surgery and who developed an orbital and myocardial relapse 2 years after the initial diagnosis. Melanotic schwannomas are rare pigmented tumours that tend to arise from the peripheral nerves near the midline. A primary lung presentation, as in our case, is extremely rare. In more than half of cases, the Carney triad of myxomas of the heart, skin and breast, spotty pigmentation and endocrine hyperactivity is present. A thorough pathological study is pivotal for a correct diagnosis. The main differential diagnosis is with metastases of malignant melanoma. The biological behaviour is unpredictable. Treatment should include radical surgery if possible; the role of chemotherapy and radiotherapy is uncertain due to the rarity of the tumour (AU)

Carcinoma of unknown primary site: development in a single institution of a prognostic model based on clinical and serum variables.

PURPOSE: To identify clinical and biologic variables with significant impact on survival in patients with carcinomas of an unknown primary site (CUP) and to develop a simple prognostic model. PATIENTS AND METHODS: In this retrospective study, univariate and multivariate prognostic factors analyses were conducted in a population of 100 patients with CUP. Patients with features requiring well defined treatments had previously been excluded. RESULTS: Overall survival (OS) was significantly related to the following pretreatment adverse prognostic clinical factors: a poor performance status (2 or 3), weight loss more than 10% in the last six months, the presence of liver metastases and more than two metastatic sites. Two biological parameters predicted a significantly shorter survival: elevated serum levels of alkaline phosphatase and of lactate dehydrogenase. In the multivariate analysis, only two independent adverse prognostic parameters were retained: a poor performance status and the presence of liver metastases. We developed a prognostic model for OS based on the following subgroups: good prognosis (PS 0 or 1 and absence of liver metastases), intermediate prognosis (PS> or =2 or presence of liver metastases) and poor prognosis (PS> or =2 or presence of liver metastases). Median OS for the three groups was 10.8, 4 and 1.9 months respectively, p<0.0001. CONCLUSION: A simple prognostic model using performance status and presence of liver metastases was developed. It allowed the assignment of patients into three subgroups with different outcomes. Treatment strategies could be adapted for each subgroup. We think that this prognostic model could be useful and should be validated in other patient series.

Carcinoma of unknown primary site: development in a single institution of a prognostic model based on clinical and serum variables

PURPOSE: To identify clinical and biologic variables with significant impact on survival in patients with carcinomas of an unknown primary site (CUP) and to develop a simple prognostic model. PATIENTS AND METHODS: In this retrospective study, univariate and multivariate prognostic factors analyses were conducted in a population of 100 patients with CUP. Patients with features requiring well defined treatments had previously been excluded. RESULTS: Overall survival (OS) was significantly related to the following pretreatment adverse prognostic clinical factors: a poor performance status (2 or 3), weight loss more than 10% in the last six months, the presence of liver metastases and more than two metastatic sites. Two biological parameters predicted a significantly shorter survival: elevated serum levels of alkaline phosphatase and of lactate dehydrogenase. In the multivariate analysis, only two independent adverse prognostic parameters were retained: a poor performance status and the presence of liver metastases. We developed a prognostic model for OS based on the following subgroups: good prognosis (PS 0 or 1 and absence of liver metastases), intermediate prognosis (PS> or =2 or presence of liver metastases) and poor prognosis (PS> or =2 or presence of liver metastases). Median OS for the three groups was 10.8, 4 and 1.9 months respectively, p<0.0001. CONCLUSION: A simple prognostic model using performance status and presence of liver metastases was developed. It allowed the assignment of patients into three subgroups with different outcomes. Treatment strategies could be adapted for each subgroup. We think that this prognostic model could be useful and should be validated in other patient series (AU)

Carcinoma broncopulmonar no microcítico que debuta con adenopatíainguinal metastática / Non microcytic bronchopulmonary carcinoma commencing with metastatic inguinal adenopathy

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[Therapy-related acute leukaemia and myelodysplastic syndrome]. / Leucemias agudas y síndromes mielodisplásicos secundarios al tratamiento oncológico.

Secondary hematological malignancies represent a severe complication of cancer treatment. Their real incidence is unknown because of the heterogeneity of primary tumors, their therapies, and their prognosis. The usual presentation is an acute leukemia or myelodysplastic syndrome. Two different diseases have been described with particular clinical and cytogenetic features, namely the one associated with alkylating drugs and that related to epipodophylotoxins. Diagnosis is based on clinical suspicion, morphological alterations and cytogenetic studies. Prognosis is uniformly dismal. Conventional chemotherapy is mainly palliative, whereas allogenic transplantation allows the cure of a small percentage of cases. Thus, potential curative therapies for solid tumors should be optimized and patients maintained in long-term surveillance programs.

Imágenes pulmonares no neoplásicas, dolor lumbar y debilidad en miembros inferiores. ¿Cómo nos aproximamos al diagnóstico oncológico? / Non neoplastic lungimages, lumbar pain and lower limbs weakness. How can we approach the oncological diagnosis?

- Propósito: Presentamos el caso de una neoplasia cuya primera manifestación es una compresión medular. La presencia de baritomas pulmonares demoró el proceso diagnóstico y terapéutico.- Caso clínico: Varón de 78 años con nódulos pulmonares de densidad metálica que presentó clínica de dolor óseo y posterior alteración motora (paraplejía). Se confirmó la existencia de lesiones líticas vertebrales con anatomía patológica de adenocarcinoma. Las lesiones pulmonares no tenían relación con las lesiones óseas. La evolución del paciente no permitió la confirmación del origen prostático pero ante un PSA elevado era la opción diagnóstica más probable.- Discusión: El 15 por ciento de las neoplasias debutan con clínica secundaria a metástasis. Un 20 por ciento de los casos de compresión medular son la primera manifestación de un tumor. El síntoma inicial suele ser dolor de espalda que precede a los síntomas neurológicos. El método diagnóstico de elección ante una sospecha de CM es la RNM. El tratamiento de la CM es de carácter urgente para evitar la progresión del deterioro neurológico. En caso de histología conocida, debe instaurarse sin demora un régimen de corticoides a altas dosis junto con RT vertebral. La cirugía hay que considerarla como primera maniobra terapéutica y diagnóstica si se desconoce la histología (AU)

Leucemias agudas y síndromes mielodisplásicos secundarios al tratamiento oncológico / Therapy-related acute leukaemia and myelodisplastic syndrome

Las neoplasias hematológicas secundarias representan una complicación grave del tratamiento oncológico. Se desconoce su incidencia real dada la heterogeneidad de los tumores primarios, su pronóstico y su tratamiento. Suelen manifestarse como leucemias agudas y síndromes mielodisplásicos y, entre ellos, destacan dos entidades nosológicas con características clínicas y citogenéticas propias: la asociada al empleo de alquilantes y aquella secundaria al uso de epipodofilotoxinas. El diagnóstico se basa en la sospecha clínica, las alteraciones morfológicas y el estudio citogenético. Su pronóstico es uniformemente desfavorable. La quimioterapia convencional tiene un objetivo paliativo y sólo el trasplante alogénico permite la curación en un número limitado de casos. Por ello deben optimizarse las pautas terapéuticas en aquellas neoplasias primarias con posibilidad de obtener largas supervivencias y mantener a los pacientes en programas de seguimiento prolongado (AU)

Gangrena gaseosa de miembros inferiores y shock séptico secundario a clostridium septicum en un paciente afecto de adenocarcinoma rectal en tratamiento con quimioterapia y radioterapia / Gas gangrene of the the lower limbs and septic shock secondary to Clostridium septicum in a patient with rectal adenocarcinoma treated with chemotherapy and radiotherapy

Introducción: Presentamos un caso de shock séptico en neutropenia causado por Clostridium septicum en un paciente en tratamiento con quimioterapia y radioterapia como tratamiento adyuvante de un cáncer de recto. Presentación del caso: El paciente presentó lesiones cutáneas equimóticas y con crepitación a la exploración, posteriormente la evolución presentó un curso fulminante con foco primario abdominal y desarrollo posterior de gangrena gaseosa en miembros inferiores asociada a shock séptico. A pesar del tratamiento con antibióticos de amplio espectro y el desbridamiento quirúrgico la evolución fue desfavorable. Discusión: La aparición de un shock séptico por Clostridium septicum debe sospecharse en pacientes con enfermedades malignas hematológicas o que afectan al aparato digestivo sobre todo si aparecen lesiones cutáneas que sugieren gangrena gaseosa. Esta infección tiene una alta letalidad y el diagnóstico precoz y el tratamiento antibiótico y quirúrgico debe ser inmediato para lograr un buen control de la enfermedad (AU)