The goal of this observational study is the creation of a national network of precision medicine, which allows to increase, for Italian patients suffering from solid tumors, the possibility of access to more innovative therapies and to collect retrospectively their clinical data.

For this purpose, a national register of actionable mutations in patients with solid tumors in advanced stage of disease will be created in which various individual, local and regional initiatives of genomic screening of cancer could merge.

The primary objective of this observational study is to describe the frequency of actionable mutations in patients with solid tumors in advanced stage, receiving a genetic-molecular characterization with high throughput methods.

The secondary objectives are:

1. assess the correlation between genetic alterations and clinical and pathological characteristics of enrolled patients (gender, age, histological variant, location and extent of neoplasm, comorbidity, familiarity for neoplasms);
2. describe, where possible, any variation in the molecular profile for patients who are subjected to genetic screening analysis at different stages of the disease.
3. record retrospectively clinical efficacy and toxicity data when patients were treated with a target therapy based on the detected molecular alterations.

The national register of actionable mutations will be created collecting the following data:

1. Data extracted retrospectively from medical records of patients that have received during the study period a test with high-throughput technologies for the molecular characterization of their tumor, either by clinical routine or for research purposes.
2. Data collected prospectively from analysis of biological samples (FFPE and biopsy liquid) of patients that meet the elibility criteria and that perform the molecular-genetic screening using Foundation Medicine services or in selected italian laboratories.
3. Clinical data collected retrospectively (RR, DOR, PFS, OS, toxicity), in case where the patients are treated with a target therapy, based on the highlighted molecular alterations and on the choice of the clinician.

Only samples already available for clinical practice will be used in the study.

The register will be limited to collecting information on molecular alterations that can then be used for the insertion of patients in clinical studies already active, for the design of new studies proposed by members of the Steering Committee or of the participating sites, or for treatment with other modality.

General Inclusion Criteria for all patients:

• Age >18 years old
• Life expectancy 6 months
• ECOG performance status 2
• Diagnosis of malignant solid tumor, in advanced stage
• Informed consent to data registration and for privacy purposes

Additional inclusion criteria for patients that have already carried out a genetic characterisation extended by high throughput methods:

● Availability of the result of the broad spectrum analysis of genetic alterations carried out with high throughput methods on biological samples

Additional inclusion criteria for patients that perform the molecular-genetic screening using Foundation Medicine services or in selected italian laboratories:

• one of the following criteria:

  • Patients diagnosed with NSCLC not squamous, not pretreated;
  • Patients with biliary tract, pancreatic, esophagus, stomach, thymus, CNS, nasopharynx, salivary glands, endometrium and urothelium cancers;
  • Patients with any disease (including NSCLC) who are progressing disease after treatment with molecular target drugs. For these patients is the availability of a post- treatment biological sample is necessary;
  • Patients with cancer of unknown primary (CUP);
  • Young patients (<40 years) or patients who have exhausted standard lines of therapy, with any advanced/metastatic tumor which, in the opinion of the investigator, may benefit from a genetic-molecular characterization at broad spectrum aimed at a treatment with molecular target therapies.

• availability of biological material for testing.

• informed consent for testing.

Additional exclusion criteria for patients that perform the molecular-genetic screening using Foundation Medicine services or in selected italian laboratories:

● patients who have already received NGS or other high throughput in the same stage of disease.

patients with solid tumors in advanced stage of disease