Lymphocyte Depletion and Change in Lymphocyte Functionality
Lymphocyte Depletion and Change in Lymphocyte Functionality
Lymphocytes are a type of white blood cell (WBC) found in the participant's blood. During
 radiation treatment, moving blood is exposed to radiation. This may cause a decrease in the
 amount of lymphocytes. A researcher at UVA has created a system to predict and reduce the
 immune cell reduction following lung SBRT treatments beyond standard of care tx in
 lymphocytes in patients with Non-Small Cell Lung Cancer (NSCLC). The predicted decrease of
 lymphocytes will be compared to the actual decrease in lymphocytes found in blood.

 Researchers have found a way to give radiation that they think will result in a smaller
 decrease in lymphocytes after radiation. There will be two groups in this study, about half
 of the participants will have their radiation designed to decrease radiation to organs with a
 lot of blood and the other half will receive standard radiation therapy.

 Participants are being asked to take part in this study because the participants have been
 diagnosed with NSCLC and will be receiving a type of radiation therapy called stereotactic
 body radiation therapy (SBRT) where high doses of radiation will be delivered to the tumor,
 while minimizing damage to healthy surrounding tissues.
Lymphopenia, a known consequence of radiation therapy to virtually every part of the body,
 was first described in the early 20th century shortly after the discovery of X-rays.
 Radiation therapy (RT) can induce lymphopenia in the absence of concomitant chemotherapy or
 steroids and even when neither bone marrow nor lymphatic tissue is included in the treatment
 field. It is highly possible that irradiation of blood rich organs such as the great vessels,
 would reduce the lymphocyte count significantly. Given this known radiation-induced toxicity,
 circulating blood should be considered an organ at risk during irradiation, and efforts
 should be made to understand the toxicity from radiation to circulating blood -normal tissue
 complication probabilities (NTCP) so that this may be included in the optimization strategy
 during radiation treatment.

 Additionally, recent data have suggested that lymphocyte subsets exhibit differential
 sensitivity to radiation, with helper CD4+ T cells being more sensitive than cytotoxic CD8+ T
 cells in glioblastoma (GBM) treated with RT and temozolomide, and naïve T cells more
 sensitive than memory T cells in prostate cancer.

 Based on existing data on the effects of irradiation on total lymphocyte count and the
 effects on subsets of T cells, the investigators have created a lymphodepletion predictive
 algorithm. In this clinical trial, the investigators will test whether optimized SBRT plans
 lead to lower lymphocyte depletion and whether the algorithm can accurately predict
 lymphocyte decreases following SBRT. Optimized SBRT plans will meet all standard of care
 dose-volume objectives for SBRT and for protection of organs-at-risk (OAR), but will also
 reduce radiation to the regional great vessels, lungs, and heart beyond what is currently
 optimized to reduce the integral dose to circulating blood/lymphocytes. This study will allow
 us to evaluate the performance of our predictive algorithm for post-SBRT decrease in
 lymphocyte count and to determine whether additional steps in SBRT planning will deliver
 lower risk of post-SBRT decreases in lymphocyte count.
Inclusion Criteria:

 1. Willingness and ability to provide written informed consent and to comply with the
 study protocol.

 2. Diagnosis of biopsy confirmed non-small cell lung cancer (NSCLC) with planned
 treatment with SBRT as definitive therapy OR imaging confirmed lung lesion for which
 SBRT is planned for primary lung cancer (when clinician determines biopsy is not
 indicated), Registration should occur within 5 business days (before or after) of
 planning CT.

 3. Patients must decline surgery or tumor(s) must be considered to be medically
 inoperable

 4. Location and size of tumor- Participants must have either:

 -  peripherally located tumors (> 2 cm in all directions from the proximal bronchial
 tree; see Figure 2 above) as defined by RTOG 0915, OR

 -  centrally located tumors (tumor size ≤ 5 cm, tumors within or touching the zone
 of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura)
 as defined by RTOG 0813.

 5. Patients with recurrence of prior surgically treated lung cancers are eligible if no
 further surgery is planned and they otherwise meet the eligibility criteria.

 6. Measurable disease on chest CT, PET CT, CT simulation at diagnosis ( must be within 8
 weeks of SBRT).

 7. Pre- radiation therapy total lymphocyte count > 0.5k/μL on blood count drawn within 2
 weeks prior to registration.

 8. In the opinion of the treating clinician, patient is medically able to tolerate the
 study SBRT treatment of 50-60 Gy in 5 fractions.

 9. ECOG performance status of 0-2.

 10. Age ≥ 18 years.

 11. If participant is a woman of childbearing potential (WOCBP), agreement to adhere to
 contraception requirements from the time of consent through completion of SBRT.

 Exclusion Criteria

 1. Prior history of radiation therapy for any reason.

 2. Systemic anti-cancer therapy within the last year prior to registration or planned use
 during or within 6 months following SBRT.

 3. Major surgery within the last 30 days before registration.

 4. Subject is a prisoner.

 5. Subject is a pregnant woman.

 6. Patient is not medically able to tolerate the study SBRT treatment of 50-60 Gy