Molecular Profiling in Tissue Samples From Patients With Cancer Who Are Exceptional Responders to Treatment

This pilot research trial studies molecular profiling in tissue samples from patients with cancer who got better with treatment that didn't work for most other patients with the same disease. Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to how well patients respond to treatment.

PRIMARY OBJECTIVES: I. To identify molecular indicators in malignant tissues from patients who were exceptional responders on clinical trials or standard systemic treatments using whole exome and/or targeted deep sequencing, as well as potentially other sequencing and other molecular characterization methods (if adequate tissue exists). II. To explore associations between the identified molecular indicators and the putative mechanism of action of the treatment received by the patient. III. To test the feasibility of identifying "exceptional responders", obtaining the relevant tumor and normal tissue and clinical data, and performing whole exome and/or targeted deep sequencing on these samples. OUTLINE: Previously collected tissue samples are analyzed via whole exome sequencing and/or targeted next generation sequencing (NGS) assay deep sequencing. Cases for which sufficient nucleic acid amounts are available will undergo additional analyses including whole genome sequencing, messenger ribonucleic acid (RNA) (mRNA)-sequencing, micro (miRNA) sequencing, promoter methylation analysis, and single nucleotide polymorphism (SNP) analysis.

Inclusion Criteria: * Documented exceptional response, defined as patients meeting the following criteria: * Complete response to a regimen in which complete response is expected in \< 10% of similarly treated patients * Partial response (PR) \> 6 months in a regimen in which PRs \> 6 months are expected in \< 10% of patients with similar disease treated with same or similar regimen * Complete response (CR) or PR of unusual duration, such that the internal review committee considers it to be an exceptional response; examples below: * PR of duration \> 3 x the median expected PR duration (in cases where PR is expected in \> 10% of patients with the same disease treated with the same regimen) * CR or duration \> 3 x the median expected CR duration (in cases where CR may be seen in \> 10% of patients with same disease treated with same regimen) * The observed duration of CR (or PR) is longer than expected for 90% of patients with same disease treated with same regimen * Note: it is not required that the patient be enrolled on a clinical trial when the exceptional response was observed * Reports of radiologic scans or other evidence documenting response will be submitted for review; cases where response is not assessable (e.g. adjuvant treatment) will not be eligible because the outcome can not be attributed to a specific treatment * Treatment history must be available, for prior treatment and for the drug to which the exceptional response occurred * Patient must meet consent criteria; this requires: (i) current exceptional responder (ER) consent by a living participant not lost to follow-up, (ii) prior consent for future research by a participant not known to be deceased, but lost to follow-up, or (iii) if patient is deceased and did not decline to participate in research at the time of tissue removal for any tissue that would be used in this study, then no consent is required * Tumor sample available that meets study requirements * Required tumor samples MUST exist and be able to be submitted; investigators wishing to submit samples must not have made agreements that would prohibit the free use of data from such samples; the National Cancer Institute (NCI) will provide investigators with a letter for the collaborator amending their existing agreement to allow for the case to be submitted * Tumor tissue from prior to administration of the drug to which the exceptional response occurred is required; ideally this sample will have been collected just prior to treatment, but other prior tissue will be considered; tissue may be fresh frozen or formalin-fixed paraffin embedded * Tumor tissue amount must be at least a core biopsy, and meet minimum specimen requirements * Encouraged: normal tissue sample: (optional): blood or other specimen source for germline sequencing * The tumor samples and clinical data submitted to the Exceptional Responders Database in database in Genotypes and Phenotypes (dbGaP) will need to have appropriate agreements in place to allow for the submission; the Exceptional Responders Database can accept clinical data and samples from cases enrolled on a Cancer Therapy Evaluation Program (CTEP) sponsored clinical trial and cases that were not enrolled on any clinical trial; if the response occurred on a trial that was not CTEP-sponsored, there are existing agreements between the submitting site and the pharmaceutical company; if existing agreements do not allow for the submission of sample and clinical data, the NCI will provide the investigators with a letter that allows the tissue to be used for the exceptional responders study if signed by the appropriate collaborator; the letter modifies the existing agreement to include the CTEP Intellectual Property (IP) Option language that would allow the case to be submitted to the Exceptional Responders Database; if the existing agreement cannot be modified and the letter cannot be signed, the proposed case will not be accepted; Note: as stated above, the patient does not need to have been enrolled on a clinical trial to be eligible for the exceptional responders study Exclusion Criteria: * Patient's response did not meet criteria for an exceptional response * Patient's treatment regimen is expected to lead to CR or durable PR in \> 10% of patients * Patient's duration of response is not \> 3 x expected median length of response * Response not evaluable or not able to be attributed to systemic treatment (e.g. adjuvant treatment) * Patient refused consent for use of tissue for research activities included in the exceptional responders study * Tumor sample from prior to the exceptional response is not available, or does not meet quality metrics