This pilot research trial studies circulating tumor deoxyribonucleic acid (DNA) in predicting outcomes in patients with stage IV head and neck cancer or stage III-IV non-small cell lung cancer. Studying circulating tumor DNA from patients with head and neck or lung cancer in the laboratory may help doctors predict how well patients will respond to treatment.

PRIMARY OBJECTIVES:

I. To evaluate the predictive value of the circulating tumor DNA for disease-free survival/progression-free survival in patients with advanced head and neck carcinoma (HNC) and non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To correlate the levels of plasma tumor DNA with the salivary tumor DNA. II. To correlate the mutations found in the circulating tumor DNA with the mutations in the tumor tissues.

III. To evaluate the association between presence and absence of circulating tumor DNA mutation with the tumor burden assessed by using the radiological findings and pre-treatment fludeoxyglucose (FDG) positron emission tomography (PET)-derived metrics: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), total glycolytic activity (TGA).

IV. To quantify tumor-specific exosomes from plasma. V. To evaluate the utility of cancer-derived exosomes to serve as prognostic biomarkers for real-time monitoring of therapeutic efficacy and identifying early recurrence using longitudinal samples from cancer patients undergoing treatment.

OUTLINE:

Patients undergo blood sample collection within 1 month before surgery, radiation therapy, or chemotherapy; within 1 week after surgical resection (for patients having upfront surgery); within 1 month before beginning of post-operative radiation therapy (for patients having upfront surgery); during the second week of radiation therapy, during the last week of radiation therapy; and at 1 and 3 months after radiation therapy and then every 3 months for up to 18 months. Patients also undergo saliva sample collection within 1 month before surgery, radiation therapy, chemoradiation therapy, or system chemotherapy and tissue collection at the time of surgery (if upfront surgery is indicated). Blood, saliva, and tissue samples are analyzed for tumor mutations via next generation sequencing.

Inclusion Criteria:

1. Patients older than 18 years age
2. Diagnosis of advanced HNC (Stage III, IVA, IVB, IVC) or NSCLC (Stage IIA, IIB, IIIA, IIIB, IV) (patients with synchronous advanced HNC and NSCLC are eligible)
3. ECOG performance status score of 0-3
4. Life expectancy of 3 months or longer
5. Patients able to provide a written informed consent prior to study entry

Exclusion Criteria:

1. Prior chemotherapy or full course of radiotherapy for their present advanced HNC or NSCLC
2. Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated basal or squamous cell carcinoma of skin
3. Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation, and in the judgment of the investigator would make the subject inappropriate for entry into this study

Patients diagnosed with advanced head and neck carcinoma or NSCLC enrolled at Thomas Jefferson University