NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms.

Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6-10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy.

Peptide Receptor Radionuclide Therapy - Prospects for Personalised Treatment.

Peptide receptor radionuclide therapy is a type of molecular radiotherapy that has been used in the treatment of patients with neuroendocrine tumours for over two decades. It is not until recently, however, that it has achieved regulatory approval. The currently approved treatment regimen is a one-size-fits-all scheme, i.e. all patients receive a fixed activity of the radiopharmaceutical (177Lu-DOTATATE) and a fixed number of treatment cycles. Several research groups around the world have studied different approaches of further improving on the results of peptide receptor radionuclide therapy, with many promising retrospective and prospective clinical studies having been published over the years. In this overview, we summarise some of the most promising strategies identified so far.

Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours.

BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. RESULTS: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22-37 mm were detectable in the 111In-SPECT images and spheres larger than 13-22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. CONCLUSIONS: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3-4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6-21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. CONCLUSIONS: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.

[Antibodies against cancer]. / Anticuerpos contra el cáncer.

Within the revolution of molecular biology in cancer, it should be pointed out the role of monoclonal antibodies clinically utilized as if they were "magic bullets". From the works of Kohler and Milstein in 1975 the evolution has been fast and its inclusion in daily clinical practice gradual. Among the more significant there is anti-CD20 that has revolutionized the treatment of lymphomas. Currently, antibodies conjugated with isotopes derived from anti-CD20 have been produced. Trastuzumab antibody against HER2/neu has opened new prospects in the treatment of breast cancer. Cetuximab antibody against EGFR has achieved good results in the treatment of chemotherapy-resistent colon cancer. Bevacizumab is perhaps the most promising antibody against solid tumors, having shown effectiveness as first line therapy in metastatic colon cancer in combination with chemotherapy.