Carcinoid crisis: The challenge is still there.

Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.

Venting percutaneous radiologic gastrostomy in malignant bowel obstruction: safety and effectiveness in a comprehensive cancer centre.

OBJECTIVE: Approximately 20% of established malignant bowel obstruction (MBO) patients do not respond to pharmacological treatment. In these cases, venting percutaneous radiologic gastrostomy (VPRG) may be useful. Existing evidence is based on retrospective studies with methodological limitations. The purpose of this study is to describe safety and effectiveness for symptom control after VPRG placement in a prospective cohort of MBO patients. METHODS: Complications of VPRG placement, symptom control, destination on discharge and survival were analysed. RESULTS: Twenty-one patients were included, 13 (61.9%) of whom were women. Mean age was 62.7 years (36-85). Local pain (n=8, 38.1%) and peristomal leakage (n=4, 19%) were the most frequent minor complications. No major complications occurred. Nausea and vomiting were relieved in most patients (n=20, 95.2%) after VPRG, and small quantities of liquid diet were introduced to these patients. Median time to death after VPRG was 13 days (IQR 8.6-17.4). Thirteen patients (61.9%) were discharged, with seven of them (33.3%) returning home. CONCLUSIONS: When pharmacological treatment fails, the use of VPRG in MBO patients may be feasible, safe and effective.

Immunotherapy-induced isolated ACTH deficiency in cancer therapy.

Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4447 cancer patients treated with ICI antibodies, 37 (0.8%) (23 men (62.2%), mean age 64.7 ± 8.3 years (range 46-79 years)) were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n = 20, 54.1%), followed by melanoma (n = 8, 21.6%). The most common ICI antibody inhibitors reported were nivolumab (n = 18, 48.6%), pembrolizumab (n = 16, 43.2%), and ipilimumab (n = 8, 21.6%). About half of the patients (n = 19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n = 10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5-12) after starting immunotherapy. The main reported symptom at presentation was fatigue (97.3%), followed by anorexia (81.8%) and general malaise (81.1%). Mean follow-up time since IAD diagnosis was 15.2 ± 12.5 months (range 0.3-55 months). At last visit, all patients continued with hormonal deficiency of ACTH. Median overall survival since IAD diagnosis was 6.0 months. In conclusion, IAD is a rare but a well-established complication associated with ICI therapy in cancer patients. It develops around 7 months after starting the treatment, mainly anti-PD1 antibodies. Recovery of the corticotropic axis function should not be expected.

Ectopic Cushing's syndrome due to thymic neuroendocrine tumours: a systematic review.

Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic review using PubMed, Embase, Scopus, Ovid Medline and Biosis Previews of all cases with ectopic CS due to thymic NETs reported in the last 40 years and describe one illustrative patient attended in our institution. Search of literature: From 162 patients, 58.6% were male and mean age was 34.6 ± 13.9 years-old. Median of symptoms until diagnosis was 6 [2-24] months and 62% had aggressive CS. Imaging was positive in 93.7% (chest X-ray), 97.8% (computed tomography), 80.7% (somatostatin receptor scintigraphy) and median tumour size was 47 [25-68.5] mm. At presentation, 18% had localized disease, 26.2% locally invasive and 55.7% advanced. Eighty-eight present underwent surgery and histological subtypes were atypical (46.7%), typical (30.4%) and carcinoma (21.7%). Tumour persisted or recurred in 70.1%, 63% received radiotherapy and 45.2% chemotherapy. Follow-up median was 26.6 [14.5-57.5] months and mortality was reported in 35.8% with median survival of 38 [19-60] months. MEN-1 mutation was referred in 3.1%. Comparatively, carcinomas had aggressive CS more frequently while atypical showed advanced disease more often. In conclusion, thymic NETs causing ectopic CS are presented as aggressive hypercortisolism in the middle aged population. The disease is commonly extended at diagnosis and persists or recurs after surgery in most patients with a short term high mortality.

Adequacy of nutritional support using computed tomography (CT) in patients with head and neck cancer (HNC) during chemo-radiotherapy (CRT).

We assessed forty HNC patients receiving treatment with curative intent. Specific quantitative muscle and fat changes were evaluated using CT. Nutrition support was provided according to ESPEN guidelines, with adjusted body weight (ABW) in overweight/obese patients used to define their nutritional targets. Linear regression models were used to evaluate clinical predictors of tissue loss. Mean overall losses were body weight (-10.5%), and CT-defined muscle (-8.4%) and fat mass (-24.8%), p < 0.001. A subset of 20 patients had high muscle loss (-14.7%) with concurrent negative energy balance as reflected by considerable fat loss (-29.7%); those tended to have higher baseline body mass index (26.2 vs. 23.3 kg/m2, p = 0.063). In multivariate regression, only ABW independently predicted muscle loss (p < 0.001) and fat loss (p = 0.002). Nutrition support according to guidelines was appropriate for a subset of patients. ABW use to set nutrition targets in overweight/obese patients would appear to be insufficient, based on large tissue losses.

Fasting plasma glucose is an independent predictor of survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. METHODS: One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and Cox proportional models and log-rank test were used. RESULTS: With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07-1.19, p < 0.001) and 31 months (HR 1.09; 95% CI 1.04-1.15; p < 0.001) respectively, for patients with FPG < 7 mmol/L. In the multivariate analysis of the entire cohort adjusted by platinum compound and comorbidities, high levels of FPG as a continuous variable (HR 1.14; 95% CI 1.07-1.21; p < 0.001), the presence of comorbidity (HR 1.72; 95% CI 1.12-2.63; p = 0.012), and treatment with carboplatin (HR 1.95; 95% CI 1.26-2.99; p = 0.002) were independent predictors for shorter OS. In additional multivariate models considering non-diabetic patients as a reference group, diabetic patients with poor metabolic control (HbA1c > 8.5%) (HR 4.53; 95% CI 2.21-9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90-5.46 p < 0.001) had significantly independent worse OS. CONCLUSION: Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association.

Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes.

PURPOSE: Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center. METHODS: All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS). RESULTS: Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35-71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2-197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17-0.94]; p = 0.035). CONCLUSIONS: TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.

NUTRISCORE: A new nutritional screening tool for oncological outpatients.

OBJECTIVES: The aim of this study was to design a new nutritional screening tool (NUTRISCORE) to detect nutritional risk in outpatients with cancer. METHODS: A multicenter, cross-sectional study was conducted. We randomly selected outpatients receiving onco-specific, palliative, or symptomatic treatment for malignant neoplasms (including solid tumors and hematologic malignancies). These patients were assessed using the NUTRISCORE tool, the Malnutrition Screening Tool (MST), and the Patient-Generated Subjective Global Assessment (PG-SGA) to detect risk for malnutrition. The new tool included questions regarding the cancer site and active treatment. Sensitivity, specificity, and positive and negative predictive values were calculated for NUTRISCORE and MST using the PG-SGA as a reference method. RESULTS: We evaluated 394 patients. According to NUTRISCORE, 22.6% were at risk for malnutrition. The MST detected a risk in 28.2%, and the PG-SGA found that 19% were malnourished or at nutritional risk. Using the PG-SGA as a reference method, the MST had a sensitivity of 84% and a specificity of 85.6%, whereas NUTRISCORE exceeded these values, at 97.3% sensitivity and 95.9% specificity. The better performance of NUTRISCORE as compared with MST was confirmed by the receiver operating characteristic curve analysis, with area under the curve values of 0.95 (95% confidence interval, 0.92-0.98) for NUTRISCORE and 0.84 (95% confidence interval, 0.79-0.89) for the MST. CONCLUSIONS: NUTRISCORE has been found to be a novel, fast, and valid nutritional screening tool for outpatients with cancer. Its simplicity and high level of accuracy in detecting nutritional risk facilitates its applicability.