*Credentialing required. Please check your site's credentialing status.*

-Pathologically proven diagnosis of Stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer NOS).
-Patients must have measurable disease;
-Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management;
-No distant metastases
-Zubrod Performance Status must be 0-1
-Patients must be at least 3 weeks from prior thoracotomy (if performed);
-Patients must not have mixed small cell and non-small cell histologies;
-No prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
-No prior radiotherapy to the region of the study cancer that would result in overlap of RT fields;
-Patients must not be currently using metformin, other oral hypoglycemic agents or insulin;

*Credentialing required. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH, Sparrow, St. Mary's Livonia, St. John Hospital, SJMO (MI254 only), St. Marys Saginaw

-Pathologically proven diagnosis of NSCLC with mets- newly diagnosed OR previously treated for stages I-III
-Zubrod PS must be 0-2
-Must have received first-line/ induction systemic therapy (at least 4 cycles) and achieved stable disease or partial response.
-Prior treatment as part of concurrent approach for previously diagnosed stage III, as adjuvant therapy for resected disease, or for other previous cancers is allowed.
-Prior RT for brain mets is allowed
-Patients must have measurable disease and 3 or fewer discrete extracranial mets that are amenable to SBRT.
-For de novo stage IV patients, primary disease must be treatable with SBRT or hypofractionated RT
-If primary disease in the thoracic cavity was previously treated by surgery or RT, any new local/regional recurrence should be treatable with SBRT or hypofractionated RT after induction systemic therapy
-Patients must be registered within 35 days of last dose of treatment
-Must not have evidence of new, untreated and/or progressive brain mets after induction systemic therapy
-Must not have cutaneous mets or metastatic disease invading the esophagus, stomach intestines, or mesenteric lymph nodes
-Must not have received targeted therapy in first-line
-Must not have unresolved malignant pleural effusions
-Patients that have had previous RT must have allowable prospective dosing

PATIENTS MAY NOT CO-ENROLL ON SWOG S1827. Co-enrollment on NRG-CC003 is allowed. 

CREDENTIALING REQUIRED. Please check your site's credentialing status.

Please check your IROC status pre-patient registration.

DTL Required- Physicians must sign the toxicity grid
CURRENT SITES CREDENTIALED: SJMH (AA,Brighton, Canton, Chelsea), Sparrow, GenHur, LVHN, St. John Hospital, St. John Macomb, SJMO (21st Century Oncology Only), Holy Cross, Livonia

**CREDENTIALING REQUIRED. Please check your site's credentialing status.**

*DTL Required- Physicians must sign toxicity grid
CURRENT SITES CREDENTIALED: SJMH (Brighton, Canton, Chelsea), St. Mary's Liviona, Genesys, Sparrow, Saginaw, Lehigh Valley (Cedar Crest, Muhlenberg)

Eligibility Criteria:

- Pathologically proven diagnosis of extensive stage small cell lung cancer;

- Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (PET/CT scan, diagnostic CT scan, MRI optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum or 6 weeks from completion of PCI.

- At the time of enrollment, patients must have had measurable disease (per RECIST) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment.

- Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging.

-Appropriate stage for study entry based on the following diagnostic workup:

• History/physical examination within 14 days prior to registration;
•  Imaging within 42 days prior to registration to include:
• MRI brain with contrast or CT Brain with contrast
• CT chest, abdomen and pelvis or whole body PET/CT scan after the fourth cycle of chemotherapy

-Age = 18;

-  ECOG Performance Status of 0-2 at the time of registration;

-  

Required laboratory values within 14 days prior to registration:

- Upfront central nervous system (CNS) radiotherapy for treatment of brain metastases is permitted provided there is no evidence of CNS progression at the time of randomization and patients are clinically stable on a dose of steroids <10 mg prednisone a day or equivalent. Upfront radiation therapy of symptomatic metastatic site is permissible if causing patient pain or impending fracture.

- Patients with bone metastases are eligible. However, to assess response after radiation for bone metastases, must order at least diagnostic CT scan to measure response.

- For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.

Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

• Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women = 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 5 years prior to randomization. Cancers with a negligible risk of metastasis or death (e.g., expected 5-year OS >90%) treated with expected curative outcome are eligible (such as adequately treated carcinoma in situ of the cervix or oral cavity; localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent);

- Prior radiotherapy except in the thorax, where there may be some overlap in the mediastinum and spine, as long as overlap fields meet dose constraints.
- History of autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn’s, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener’s granulomatosis; Sjögren’s syndrome; Guillain-Barré syndrome; multiple sclerosis; vasculitis; or glomerulonephritis. Note: the follow are eligible:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
• Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
o Patients with psoriasis must not have ocular manifestations within the past year

o Rash must cover less than 10% of body surface area (BSA)
o Disease is well controlled on topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
o No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or oral steroids)
- Severe, active co-morbidity defined as follows:
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
• Active tuberculosis;
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease. 

i. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
ii. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. (The HCV RNA test must be performed for patients who have a positive HCV antibody test.)

-Known immunosuppressive disease, for example history of bone marrow transplant or CLL;
- Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
o A stable regimen of highly active anti-retroviral therapy (HAART)
o No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
o A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests 

• Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary;
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months;
• History of recent myocardial infarction within 6 months prior to registration.
• Clinically significant interstitial lung disease

- Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

- Women who are breastfeeding and unwilling to discontinue.

- Patients who have had immunotherapy-induced pneumonitis.

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (Ann Arbor, Brighton, Chelsea, Livonia), Sparrow, SJMO

**Canton cannot participate due to SBRT arm.

Eligibility Criteria:

3.1.1 Pathologically (histologically or cytologically) proven diagnosis of Stage II or III (AJCC Eighth Edition) non-small cell lung cancer (NSCLC) with known PD-L1 status prior to registration.

• Patients must have an identified primary tumor and at least one nodal metastasis (peribronchial/hilar/intrapulmonary, mediastinal/subcarinal, supraclavicular/scalene)
• Up to 4 cycles of systemic therapy received prior to registration for the current study cancer is allowable; any prior chemotherapy for a different cancer is also permissible.

3.1.2 The patient must be deemed clinically appropriate for curative intent definitive combined modality therapy, based on the following staging assessments:

• History/physical examination prior to registration;
• MRI scan of the brain (preferred) or CT scan of the brain (if available, contrast is preferred for all neuroimaging) prior to registration;
• CT chest with IV contrast (if contrast is available and unless contraindicated, such as for abnormal kidney function) prior to registration. PET/CT may be used if the CT portion is of identical diagnostic quality as achieved in a stand-alone CT.

3.1.3 No evidence of distant metastases based on FDG PET/CT scan obtainedwithin 60 days of registration.

3.1.4 Primary tumor ≤ 7 cm;

3.1.5 Age ≥ 18;

3.1.6 ECOG performance status 0-2;

3.1.7 Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the discretion of the treating physician, to allow for treatment with chemotherapy and concurrent radiation therapy;

3.1.8 Adequate renal function: Creatinine clearance ≥ 25 mL/min by the Cockcroft-Gault

3.1.9 Subjects with non-malignant pleural effusion are eligible provided the effusion is not known or demonstrated to be an exudative effusion.

• If a pleural effusion is present, the following criteria must be met to exclude malignant involvement: o When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative; o Effusions that are minimal (i.e., not visible on chest x-ray) that are too small to safely tap are eligible.

3.1.10 Medical history consistent with the patient being amenable, at the discretion of the treating physician, to allow for treating with consolidation immunotherapy. Patients with known EGFR/ALK mutation at the time of registration are eligible, and these patients can be treated with consolidation durvalumab or chemotherapy at the discretion of the treating physician.

3.1.11 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.

3.1.12 Negative pregnancy test ≤ 14 days prior to registration for participants of childbearing potential; 3.1.13 The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.

**PLEASE SEE THE CURRENT VERSON OF PROTOCOL FOR FULL RLGIBILITY LIST**

**E11LAB CTA 7/3/15 JH 

1. Histologically confirmed adenocarcinoma of the breast

2. Hormone receptor status: estrogen and/or progesterone receptor positive tumor Her2/neu negative tumor by either fluorescent in situ hybridization (FISH) or immunohistochemistry (e.g., 0 or 1+ by DAKO Herceptest)

3. Must have undergone surgery to remove the primary tumor by either a modified radical mastectomy or local excision plus an acceptable axillary procedure (i.e., sentinel lymph node biopsy and/or axillary dissection) within the past 84 days

4. Must have adequate (i.e., ¡Ý 1 mm, if margin width specified) tumor-free margins of resection for invasive and ductal carcinoma in situ; Lobular carcinoma in situ involving the resection margins are allowed

5. Negative axillary nodes as determined by a sentinel lymph node biopsy and/or axillary dissection

6. Lymph nodes that are negative by H & E staining but positive by immunohistochemistry or molecular techniques are considered negative

7. Tumor size 1.1-5.0 cm

8. Tumors that measure 5 mm-1.0 cm are allowed provided there are unfavorable histological features, defined as intermediate or poor nuclear and/or histologic grade or lymphvascular invasion

9. Pathologic tumor size should be used; If microscopic measurement is used and tumor includes ductal carcinoma in situ, the measurement should include only the invasive component of the tumor

10. Tissue specimen from the primary tumor available for diagnostic testing with Oncotype DX to determine Oncotype Recurrence Score

11. No prior Oncotype DX Assay unless patient has a recurrence score of 11-25

12. Patients who develop breast cancer while receiving a selective estrogen-receptor modulator (SERM) (e.g., tamoxifen, toremifene, or raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole, or exemestane) for breast cancer prevention or a SERM for other indications (e.g., raloxifene for osteoporosis) are ineligible

13. No prior ipsilateral or contralateral invasive breast cancer, bilateral synchronous cancers, or prior ipsilateral or contralateral ductal carcinoma in situ



Prior/Concurrent Therapy:

1. No prior chemotherapy or radiotherapy for this cancer

2. Prior SERM or aromatase inhibitor therapy that was administered for up to 8 weeks for this cancer is allowed

3. No concurrent radiotherapy with chemotherapy

4. Concurrent enrollment on another CTSU study allowed provided patient is already enrolled on ECOG-PACCT-1 and the treatment options in the other study are consistent with PACCT-1-specified treatment assignment (i.e., chemohormonal therapy or hormonal therapy alone)



Patient Characteristics:

1. Female only

2. Any menopausal status allowed

3. WBC count ¡Ý 3,500/mm3

4. Platelet count ¡Ý 100,000/mm3

5. Creatinine ¡Ü 1.5 mg/dL

6. AST ¡Ü 3 times upper limit of normal

7. Life expectancy ¡Ý 10 years

8. No chronic obstructive pulmonary disease requiring treatment

9. No chronic liver disease (e.g., cirrhosis or chronic active hepatitis)

10. No history of cerebrovascular accident

11. No history of congestive heart failure or other cardiac disease that would contradict the use of an anthracycline (e.g., doxorubicin hydrochloride or epirubicin)

12. No chronic psychiatric condition or other condition that would preclude study compliance

13. Not pregnant or nursing

14. Negative pregnancy test; Fertile patients must use effective nonhormonal contraception (e.g., intrauterine device, condoms, diaphragm, abstinence)

15. No other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

 *Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Livonia, Macomb, Oakland, Oakwood, Saginaw, Sparrow, St. Alphonsus, St. John, SJMH, Lehigh
NOTE: the QOL substudy is closed to accrual, as the accrual goal for this component has been met.
-Pathologically proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations:
--Gleason score 7-10 + T1c-T2b (palpation) + PSA < 50 ng/mL (includes intermediate- and high-risk patients)
--Gleason score 6 + T2c-T4 (palpation) or > 50% (positive) biopsies + PSA < 50 ng/mL
--Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL
-Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT or MR), (but not by nodal sampling, or dissection) within 90 days prior to registration.
-Patients status post a negative lymph node dissection are not eligible
-No evidence of bone metastases (M0) on bone scan
-Zubrod performance status must be 0-1
-Must not have had prior radical surgery or cryosurgery for prostate cancer
-Must not have had previous pelvic RT, prostate brachytherapy, bilateral orchiectomy, or any RT that would result in overlap of RT fields
-Must not have had previous hormonal therapy, such as LHRH antagonist, anti-androgens, or estrogens
-No use of finasteride within 30d prior to registration
-No use of dutasteride or dutasteride/tamsulosin within 90d prior to registration
-No previous or concurrent cytotoxic chemotherapy for prostate cancer     

**Cosmesis subset is closed to accrual for ALL newly enrolled patients**

**Regarding the strat factor for chemotherapy, answer "yes" for patients who have received chemotherapy previously and "no" for patients who have not received chemotherapy yet.  The registration worksheet is confusing, as it asks if the patient is "intending to receive chemotherapy", but this should be ignored. (Per RTOG, an amendment is coming out to remove this language)**

**See Section 5.0 for registration and credentialing information**