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Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1) do mutations in the target/pathway confer resistance? (2) Are these mutations pre-existing? (3) What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC). We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g) and regression (d, decay) of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor) antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.

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OBJETIVOS: Auditar la calidad de la atención brindada por nuestra consulta externa (CE) de Cuidados Paliativos (CP) tras su creación mediante la incorporación de un modelo de trabajo de cuidados paliativos precoces (CPP), y comparar nuestra experiencia con la recogida en la literatura. MATERIAL Y MÉTODOS: Presentamos un estudio descriptivo observacional retrospectivo en el que analizamos a 100 pacientes consecutivos con cáncer avanzado atendidos en nuestra CE en 2013. Se analizan los casos a través de 20 variables seleccionadas por consenso, y agrupadas en 6 categorías (datos demográficos [2], datos del tumor [1], derivación a CE [1], diagnósticos clínicos CE [6], datos de actividad CE [7], datos de impacto CE [3]). RESULTADOS: La edad media de los pacientes atendidos fue de 75 años, y el 38% padecía cáncer de pulmón. Un 17% de los pacientes cumplía criterios completos de CPP y otro 26%, criterios parciales. Tan solo un 33% de los pacientes cumplía criterios tradicionales de cáncer en situación terminal. Se han detectado diagnósticos clínicos novedosos en la muestra: hipovitaminosis D 35%, insuficiencia suprarrenal 18%, hipogonadismo 5%, encefalopatía quimioterápica y rádica 4%, conductas aberrantes asociadas al consumo de opioides 2%. Los pacientes precisaron una media de 3,5 visitas a la CE y 1,14 revisiones telefónicas, y la supervivencia media hasta el fallecimiento fue de 3,7 meses. Los pacientes derivados en tratamiento con quimioterapia (QTP) que cumplían criterios completos de CPP precisaron de más revisiones presenciales (media 6,12), y presentaron una supervivencia media de 7,7 meses. El 82% de los pacientes precisó de procedimientos diagnósticos o terapéuticos de ámbito hospitalario y el 31% recibió radioterapia paliativa. Dos tercios de los pacientes precisaron de ingreso en las camas de la Unidad de Cuidados Paliativos de agudos en algún momento en su evolución, y la mayoría fallecieron en la misma (44 pacientes para 56 fallecimientos). El número de visitas a Urgencias en el último mes de vida fue bajo (39 visitas para 56 pacientes), siendo bajo también el número de pacientes tratados con QTP en el último mes de vida (5,3%). DISCUSIÓN: El análisis no estadístico sugiere que la CE atiende a una población de procedencia y supervivencia variadas, pero con la característica común de una elevada complejidad en sus necesidades paliativas. Los datos preliminares no contradicen la hipótesis vigente, que afirma que los CPP pueden generar ahorros en el gasto sanitario. CONCLUSIONES: Nuestra experiencia inicial con una CE de CP sugiere que la aplicación de los CPP es posible en nuestro entorno. Por otro lado, nuestros resultados preliminares no parecen poner en tela de juicio ninguno de los posibles beneficios ya conocidos con la implementación de los novedosos programas de CPP

OBJECTIVE: To audit the quality of care delivered in our Outpatient Clinic (OC) after its inception following an early palliative care (EPC) model, and to compare our experience with the relevant literature. MATERIAL AND METHODS: A descriptive observational retrospective study was conducted on 100 consecutive advanced cancer patients who attended our OC in 2013. The cases are analyzed using 20 variables selected by consensus, and grouped into 6 categories (demographics [2], primary tumor [1], access to OC [1], OC clinical diagnoses [6], OC activity [7], impact [3]) RESULTS: The mean age of the patients was 75 years, and 38% suffered from lung cancer. EPC criteria were completely fulfilled by 17%, and a further 26% partially fulfilled them. Only 33% of the patients would be considered traditional terminal cancer PATIENTS: Emerging clinical diagnoses were found in the sample: vitamin D deficiency 35%, adrenal insufficiency 18%, hypogonadism 5%, chemotherapy and radiotherapy induced encephalopathy 4%, aberrant opioid related behaviors 2%. The average number of visits to the OC was 3.5, plus an average of 1.14 telephone consultations, and the median follow-up among patients who died was 3.7 months. Patients on chemotherapy (CTP) who completely fulfilled EPC criteria had a higher average number of visits (6.12), and survived longer until death (7.7) months.complex hospital diagnostic and therapeutic procedures were required in 82% of the patients, and 31% received palliative radiotherapy. Two thirds of the patients were admitted to the inpatient acute Palliative Care Unit at any given point during follow-up, and the majority died in the Unit beds (44 patients out of 56 deaths). The number of visits to the emergency department within 30 days of death was low (39 visits for 56 patients), and CTP within 30 days of death was also low (5.3%). DISCUSSION: The non-statistical analysis suggests that the OC attends a population with a varied survival and origin, but with the common characteristics of complex palliative care needs. Our preliminary data do not contradict current hypothesis suggesting that EPC might be cost saving. CONCLUSIONS: Our initial experience with an OC suggests that an EPC model is feasible in our own environment. On the other hand, our preliminary data does not fail to support the potential benefits associated with the implementation of EPC

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