** Temporarily Closed p16-positive OPC/CUP Cohort Effective 10/07/2024**

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (Ann Arbor, Brighton, Chelsea, Canton), St. Mary's Livonia, Genesys, St Joseph Mercy Oakland

Eligibility Criteria:

-A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

-Pathologically (histologically or cytologically) proven diagnosis of SCCHN of the oropharynx, larynx, hypopharynx, or p16-positive unknown primary prior to registration; specimen from cervical lymph nodes with a well-defined primary site documented clinically or radiologically is acceptable; in patients with carcinoma of unknown primary this will be sufficient for pathologic confirmation without a clinically or radiographically defined primary site. For patients with oropharyngeal cancer (OPC)/cancer of unknown primary (CUP): P16 status based on local site immunohistochemical tissue staining is required. A cell block obtained from a fine needle aspiration (FNA) biopsy specimen may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification. Note: Institutions must screen patients for p16 status by immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the U.S. CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable. The p16 results must be reported on the pathology report being submitted. The p16 positivity is defined as > 70% of tumor cells showing strong nuclear and/or cytoplasmic immunostaining with p16 antibody. For patients with laryngeal and hypopharyngeal primaries: Analysis of p16 status is NOT required;

- Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions.  

-Clinical stage (AJCC, 8th ed.) as indicated in the tables below, including no distant metastases based on the following diagnostic workup:  

• History/physical examination within 60 days prior to registration;

• One of the following imaging studies is required within 60 days prior to registration:

1. CT scan of neck (diagnostic quality with contrast, unless contraindicated) OR

2. MRI of the neck (diagnostic quality with contrast, unless contraindicated) OR

3. FDG-PET/CT of the neck; the CT component should be of diagnostic quality with contrast, unless contraindicated. Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck performed for the purposes of radiation planning may serve as both staging and planning tools.

• One of the following imaging studies is required within 60 days prior to registration:

1. FDG-PET/CT of the chest; FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility. OR 2. Chest CT

• Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration;

 The following formula is used to calculate the pack-years during the periods of smoking in the patient’s life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history. Number of pack-years = [Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)] / 20

- Age ≥ 18;

- Zubrod (ECOG) performance status of 0-1 within 14 days prior to registration;

- Adequate hematologic function within 30 days prior to registration defined as follows:

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

• Platelets ≥ 75,000 cells/mm3

• Hemoglobin ≥ 8.0 g/dL

(Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable).

- Adequate renal function within 30 days prior to registration defined as calculated creatinine clearance (CrCl) ≥ 50 mL/min by the Cockcroft-Gault formula: CrCl (mL/min) = [140 – age (years)] x weight (kg) {x 0.85 for female patients} 72 x serum creatinine (mg / dL) 3.1.8 Adequate hepatic function within 30 days prior to registration defined as follows:

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (not applicable to patients with known Gilbert’s syndrome);

• AST and ALT ≤ 1.5 x institutional ULN.

- Known human immunodeficiency virus (HIV) infected patients on effective antiretroviral therapy with undetectable viral load within 6 months and CD4 T Cell count > 200 cells/mm3 are eligible for this trial. Testing is not required for entry into protocol.

- 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 are eligible for this trial. 

- Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.

- Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 14 months (females); for 11 months (males) following last dose of cisplatin; this inclusion is necessary because the treatment in this study may be significantly teratogenic (See Section 9 for definition of highly effective contraception).

- 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.

2 Ineligibility Criteria Patients with any of the following conditions are NOT eligible for this study.

- Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of unknown primary (CUP);

- Recurrence of the study cancer;

- Definitive clinical or radiologic evidence of distant metastatic disease; 3.2.4 Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, any prior exposure to cisplatin is excluded;

- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;

- Severe, active co-morbidity defined as follows:

• Unstable angina requiring hospitalization in the last 6 months;

• Myocardial infarction within the last 6 months;

• New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.);

• Persistent Grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing;

• Patient must not have an active infection requiring IV antibiotics prior to registration;

• Other chronic renal disease like nephrotic syndrome, that could be worsened by cisplatin therapy;

• History of allogenic organ transplantation;

• Any symptomatic peripheral sensory neuropathy Grade ≥ 2 (CTCAE version 5.0);

- Pregnancy and individuals unwilling to discontinue nursing. 

-Inclusion of Women and Minorities NIH policy requires that women and members of minority groups and their subpopulations be included in all NIH-supported biomedical and behavioral research projects involving NIH-defined clinical research unless a clear and compelling rationale and justification establishes to the satisfaction of the funding Institute & Center (IC) Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances must be designated by the Director, NIH, upon the recommendation of an IC Director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research. Please see http://grants.nih.gov/grants/funding/phs398/phs398.pdf

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

CURRENT SITES CREDENTIALED:

St. Alphonsus, SJMO 

-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

QOLs are required  -can be done on paper or ePRO. ePRO is optional

- Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, M0, AJCC Staging, 8th Ed.), within 60 days prior to registration

- Patients must have received one pre-registration cycle of platinum/etoposide chemotherapy prior to study entry, with study registration required within 21 days from day 1 of the pre-registration cycle of chemotherapy and protocol treatment designed to begin 21 days after. If patient has not recovered from pre-registration cycle chemotherapy toxicities, then an additional 14 days is permitted.

- Patients must have had measurable disease (per RECIST, version 1.1) prior to the required pre-registration cycle of platinum/etoposide chemotherapy.

-  Minimal staging requirements include:

     • History/physical examination within 30 days prior to registration;

     • PET/CT scan for staging within 45 days prior to registration;

     • CT chest/abdomen with IV contrast (unless contraindicated based on kidney function)    within 45 days prior to registration – this can be obtained as part of PET/CT if CT imaging is of diagnostic quality;

• MRI scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration

-  ECOG Performance Status of 0-2 within 30 days prior to registration

- 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.

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

- Patient cannot have a definitive clinical or radiologic evidence of metastatic disease 

- Patient cannot have a definitive surgical resection of small cell lung cancer

- Patient could not have had prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

- Patient cannot have more than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable

- Patient cannot have prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study PIs.

- Patients with cytologically positive pleural or pericardial fluid are not eligible.

- Patient cannot have an active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.

- Patient cannot have active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)

- Patient cannot have a history of allogeneic organ transplant

- Patient cannot have a history of primary immunodeficiency

- Patient cannot have a severe, active co-morbidity defined as follows: 

• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;

• 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;

• Active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen (HBsAg) test, a positive anti-HBc [antibody to hepatitis B core antigen], and a negative viral DNA test (only obtained if HBsAg is found positive) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

• Known immunosuppressive disease, for example history of bone marrow transplant or CLL;

• CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count = 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.

• 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;

• Transmural myocardial infarction within the last 3 months;

• Clinically significant interstitial lung disease

**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

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:

ANC	=1,000/cells/mm3
Platelets	=75,000 cells/mm3
Hemoglobin	=8 g/dL
Total Bilirubin	=1.5 x ULN
AST (SGOT) and ALT (SGPT)	=3.0 x ULN (AST and/or ALT =5 ULN for patients with liver involvement)
Alkaline phosphatase	=2.5 × ULN (=5 ULN for patients with documented liver involvement or bone metastases)
Serum Creatinine	=2.0 x ULN
Adequate renal function	Adequate renal function within 30 days prior to registration defined as follows: Glomerular filtration rate (GFR) = 40 mL/min/1.73 m2 (See Appendix I for eGFR calculations)

- 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.

Ineligibility Criteria:

Patients with any of the following conditions are NOT eligible for this study.

- Metastatic disease invading the liver (>3 metastases), heart or >10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan count as one site. For site of bony metastases, must order diagnostic CT scan for assessment of response.

- 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.

- History of allogeneic organ transplant.

- 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

**Open to St. Joseph Mercy Hospital Ann Arbor Only**

Inclusion:
*Histologically proven adenocarcinoma of the prostate-biopsy within one year of CyberKnife treatment
*Gleason score 2-6 (pathology will be reviewed at the BIDMC)
*Clinical Stage T1-T2a
*PSA = 10 ng/ml
*Ultrasound gland size =80 cc
*ECOG/Zubrod performance status 0-1
*AUA score =15
*No prior radiation to pelvis
*No malignancy other than non-melanoma skin cancer in the past year, no history of any other cancer within the last 5 years
*Signed study-specific informed consent prior to entry on study
*No prior hip replacement surgery
*No prior LH-RH antagonist therapy 6 months prior to therapy. Up to six months of LH-RH antagonist therapy is permitted for prostate downsizing for patients who present with initial prostate size greater than 80.0 cc’s

NO EXCLUSION CRITERIA

1.) Histo or cyto proven NSCL, T1-3, N2
2.) Biopsy proven nodes.
3.) PS 0-1.

Drugs: Cisplatin, VP-16.