Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department

Introduction: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. Materials and methods: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. Results: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. Conclusion: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia

Frequency and Clinicopathological Profile Associated with Braf Mutations in Patients with Advanced Melanoma in Spain

Real-world data on BRAF mutation frequency in advanced melanoma are lacking in Spain. Moreover, data available on clinicopathological profile of patients with advanced BRAF-mutant melanoma are currently limited. This study aimed to assess the frequency of BRAF V600 mutations in Spanish patients with advanced or metastatic melanoma and to identify clinical and histopathological features associated with BRAF-mutated tumors. A multicenter, cross-sectional epidemiological study was conducted in 33 Spanish hospitals in adult patients with stage IIIc/IV melanoma. A total of 264 patients were included. The median age was 68 years and 57% were male. Melanoma mainly involved skin with intermittent (40.4%) and low or no sun exposure (43.5%). Most patients (85.6%) had stage IV disease (M1a: 19.3%; M1b: 13.3%; M1c: 22.7%). Serum lactate dehydrogenase levels were elevated in 20% of patients. Superficial spreading melanoma was the most frequent histological type (29.9%). Samples were predominantly obtained from metastases (62.7%), mostly from skin and soft tissues (80%). BRAF mutation analysis was primarily performed using the Cobas 4800 BRAF V600 Mutation Test (92.8%) on formalin-fixed, paraffin-embedded tissue (95.8%). BRAF mutations were detected in 41.3% of samples. Multivariate analysis identified age (odd ratio [OR] 0.975) and stage IV M1a (OR 2.716) as independent factors associated with BRAF mutation. The frequency of BRAF mutations in tumor samples from patients with advanced or metastatic melanoma in Spain was 41.3%. BRAF mutations seem to be more frequent in younger patients and stage M1a patients. This study provides the basis for further investigation regarding BRAF-mutated advanced melanoma in larger cohorts.This study was sponsored by Roche Farma S.A

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Implicaciones de la biopsia selectiva del ganglio centinela en la estadificación del melanoma cutáneo

El melanoma es la neoplasia maligna cuya incidencia aumenta más rápidamente en el mundo. Hasta un 15-20% de los pacientes con melanoma en estadio inicial desarrollarán metástasis ganglionares. En la situación de adyuvancia, el principal cambio referido a la estadificación surgió en los 90 con la descripción (Morton et al) de la técnica de la biopsia selectiva del ganglio centinela (BSGC). Su principio consiste en la detección, exéresis y análisis anatomopatológico del primer ganglio al que drenarían las células tumorales; la ausencia de éstas, aseguraría en gran medida, la ausencia de diseminación de la enfermedad, evitando así linfadenectomías y su morbilidad. Actualmente la BSGC ha demostrado ser factor pronóstico correlacionándose su realización con la supervivencia libre de enfermedad en pacientes con melanomas finos y de grosor intermedio. En España actualmente el único tratamiento adyuvante aceptado en melanoma es el interferón alfa 2b, en esquema de altas dosis y en pacientes en estadio IIB o en estadio III (con afectación ganglionar), por lo que la positividad de la BSGC implica un cambio de estadio y, por tanto, de propuesta terapéutica. Si bien diversos estudios valoran el impacto de la BSGC sobre el pronóstico final de los pacientes, poco se sabe de cómo ha cambiado esta práctica en la estadificación de los pacientes y si esta modificación del estadio implica un cambio en la decisión en cuanto al tratamiento a realizar y al pronóstico final de los pacientes. Objetivos: se pretende determinar las variables que se relacionan con la realización de la BSGC en la práctica clínica en pacientes con melanoma cutáneo, conocer si la positividad de la BSGC determina que los pacientes sean tratados en adyuvancia con interferón, conocer si en los pacientes que reciben interferón debido al resultado de la BSGC se mejora el pronóstico con respecto a los pacientes que no reciben interferón tras la BSGC y definir las características de los pacientes que recaen y de las recaídas dependiendo de si se realiza o no la BSGC. Material y métodos: Se realizó un estudio observacional de cohortes, no intervencionista, con un diseño analítico longitudinal con carácter ambidireccional en la Sección de Oncología Médica del Hospital General Universitario Santa Lucía incluyendo en el análisis a los pacientes diagnosticados de melanoma en estadio inicial sin afectación clínica ganglionar. El primer caso incluido fue diagnosticado el 02/09/96 y el último el 24/09/15. Se analizaron las variables relacionadas con la realización de la BSGC, con el cambio de estadio y de propuesta de tratamiento, de pronóstico y las características de las recaídas. Conclusiones: En la serie presentada las variables que se relacionan con la realización de la BSGC en la práctica clínica en pacientes con melanoma cutáneo son la presencia de melanomas nodulares, de melanomas ulcerados, un índice de Breslow mayor o igual a 1, un índice de Clark III o IV y un número de mitosis ≥1/mm2. La realización de la BSGC determina que los pacientes sean tratados en adyuvancia con interferón en al menos un tercio de todos los pacientes que finalmente reciben interferón tras el diagnóstico inicial de melanoma. No es posible demostrar una mejoría del pronóstico en los pacientes que reciben tratamiento adyuvante con interferón con respecto a los pacientes que no lo reciben tras una biopsia selectiva del ganglio centinela positiva. No es posible encontrar diferencias ni en las características de los pacientes que recaen ni en las características de la recaída dependiendo de que se realice o no la BSGC. Introduction: Melanoma is the malignant neoplasm whose incidence increases most rapidly in the world. Up to 15-20% of patients with early-stage melanoma will develop nodal metastases. The main change related to staging on the adjuvant setting, arose in the 1990s, with the description by Morton et al about the technique of sentinel node biopsy (SNB). Its principle consists in the detection, resection and anatomopathological analysis of the first nodal to which the tumor cells would drain; The absence of these would ensure the absence of dissemination of the disease, thus avoiding lymphadenectomies and their morbidity. SNB is a prognostic factor correlating its achievement with disease-free survival in patients with thin and intermediate thickness melanomas. In Spain currently, the only accepted adjuvant treatment in melanoma is interferon alpha 2b, in a high-dose regimen and in patients with stage IIB or stage III (with nodal involvement), so that the positivity of SNB involves a change of stage and, therefore, a therapeutic proposal. Although several studies assess the impact of SNB on patients' final prognosis, little is known about how this practice has changed in patient staging and whether this change implies a modification in the treatment decision or the final prognosis of patients. Objectives: To determine the variables related to the performance of SNB in clinical practice in patients with cutaneous melanoma, to know if the positivity of SNB determines the adjuvant treatment with interferon, to know if the patients who receive interferon due to the SNB result improves the prognosis respect to patients who do not receive interferon after SNB, and define the characteristics of relapsing patients and of relapses depending on SNB was done or not. Material and methods: A non-interventional, observational cohort study with a longitudinal analytical design with an ambi-directional character was performed in the Sección de Oncología Médica del Hospital General Universitario Santa Lucía, of patients diagnosed with melanoma without affectation lymph node. The first case included was diagnosed on 02/09/96 and the last on 09/24/2015. We analyzed the variables related to the performance of the SNB, with the change of stage and treatment proposal, prognosis and characteristics of relapses. Conclusions: In this series, variables related to the performance of SNB in clinical practice in patients with cutaneous melanoma are the presence of nodular or ulcerated melanomas, a Breslow index ≥1, an index of Clark III or IV and a number of mitosis ≥1/mm2. The completion of the SNB determines that patients are treated in the adjuvant setting with interferon in at least one-third of all patients who finally receive interferon after the initial diagnosis of melanoma. It is not possible to demonstrate an improvement in prognosis in patients receiving adjuvant interferon therapy with respect to patients who do not receive it following a positive sentinel node biopsy. It is not possible to find differences in the characteristics of the relapsed patients or in the characteristics relapse depending on whether the SNB is done or not

Phase II Trial of Oxaliplatin and Capecitabine After Progression to First-Line Chemotherapy in Androgen-Independent Prostate Cancer Patients

[EN] Introduction: Docetaxel plus prednisone is the current standard of care in first-line chemotherapy for metastatic hormone-refractory prostate cancer. However, there is no agent proven as effective after progression to standard docetaxel-based therapy. Platins and capecitabine have shown activity in this setting. Patients and Methods: A total of 14 patients were included in this prospective, single-center trial. All patients had progressed to first-line docetaxel-based treatment. Patients received oxaliplatin 100 mg/sqm on D1 and capecitabine 1000 mg/sqm/bid on days 1 to 14 every 21 days. Results: Median number of cycles was 3. No unexpected toxicity was observed. Only grade 3 toxicity reported was grade 3 anemia. Of the 14 patients, 3 presented grade 2 neuropathy which was spontaneously resolved. Prostate-specific antigenresponse rate was 57%, with a median time to progression of 14.5 weeks, and overall survival of 24 weeks. Conclusions: In the second-line setting, after receiving docetaxel-based chemotherapy, the combination of oxaliplatin and capecitabine offers promising activity with an excellent safety profile.Gasent Blesa, JM.; Giner Marco, V.; Giner-Bosch, V.; Cerezuela Fuentes, P.; Alberola Candel, V. (2011). Phase II Trial of Oxaliplatin and Capecitabine After Progression to First-Line Chemotherapy in Androgen-Independent Prostate Cancer Patients. American Journal of Clinical Oncology. 34(2):1-5. https://doi.org/10.1097/COC.0b013e3181d6b453S1534