Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer
- Conditions
- Muscle Invasive Bladder CarcinomaBladder Urothelial CarcinomaStage II Bladder Cancer AJCC v8Stage IIIA Bladder Cancer AJCC v8
- Interventions
- Procedure: Biopsy of BladderProcedure: Computed TomographyProcedure: CystoscopyProcedure: Magnetic Resonance ImagingOther: Quality-of-Life AssessmentRadiation: Radiation TherapyOther: Survey AdministrationProcedure: Transurethral Resection of Bladder Tumor
- Registration Number
- NCT03775265
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare bladder intact event-free survival (BI-EFS) for concurrent chemoradiation therapy (CRT) with and without atezolizumab in localized muscle invasive bladder cancer (MIBC).
SECONDARY OBJECTIVES:
I. To compare overall survival between the two arms. II. To compare modified bladder intact event-free survival including cancer related death between arms.
III. To compare complete and partial pathologic response between arms at 3 months after completing chemoradiation therapy.
IV. To estimate metastases-free survival by arm. V. To compare the qualitative and quantitative adverse events from each arm. VI. To estimate the rate of non-muscle invasive bladder cancer recurrence by arm.
VII. To estimate the rate of salvage cystectomy and reasons for cystectomy by arm.
VIII. To compare mean patient-reported global quality of life (QOL) at week 54 using the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 Global Health Status (GHS) subscale score between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with versus (vs.) without atezolizumab.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To test the hypothesis that a panel of validated biomarkers of concurrent CRT involving nuclear MRE11, impaired deoxyribonucleic acid damage response (DDR) function and tumor subtyping will be prognostic for BI-EFS among patients receiving either concurrent CRT or chemoimmuno-radiotherapy (CIRT) of the primary tumor.
II. To test the hypothesis that tumor total mutation burden, neoantigen burden, infiltrating immune response, PD-L1 expression and T cell response are associated with augmented response after concurrent CIRT.
III. To bank urine specimens for future use.
PATIENT-REPORTED OUTCOMES (PROs) OBJECTIVES:
I. To compare mean patient-reported global QOL as measured by the EORTC QLQ-C30 Global Health Status subscale scores at week 54 between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with vs. without atezolizumab. (Primary) II. To compare mean patient-reported bowel symptoms at each assessment time by arm using the Expanded Prostate Cancer Index Composite (EPIC) Bowel Assessment from the Expanded Prostate Index, the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-Muscle Invasive Bladder Cancer (BLM30), the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EuroQol Five Dimension Five Level Scale (EQ-5D-5L). (Exploratory) III. To compare longitudinal change over time by arm in patient-reported global QOL using the EORTC QLQ-C30, the Bowel Domain of the Expanded Prostate Index (EPIC Bowel Assessment), the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-BLM30, the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EQ-5D-5L. (Exploratory)
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo radiation therapy (RT) (3 dimensional \[D\] CRT or intensity-modulated radiation therapy \[IMRT\]) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine intravenously (IV) twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a transurethral resection of bladder tumor (TURBT) with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6 months through year 5 and computed tomography (CT) or magnetic resonance imaging (MRI) at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.
ARM II: Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6 months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.
After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 475
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STEP 1 REGISTRATION: If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
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STEP 2 RANDOMIZATION: If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
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Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 120 days prior to randomization and no intervening treatment between the histologic proof and randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI] of abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
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Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat office cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. This cystoscopy can be performed in urologist office without general anesthesia. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease
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Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
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Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
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Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
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Patients must not have diffuse CIS based on cystoscopy and biopsy.
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Patient must be planning to receive one of the protocol specified chemotherapy regimens.
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All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2 prior to randomization.
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Patient must not have received any systemic chemotherapy for their bladder cancer.
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Patient must not have had prior pelvic radiation.
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Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
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Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical bacillus Calmette-Guerin (BCG), interferon, and intravesical chemotherapy are allowed.
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Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:
- Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
- Immunotherapy not specified in this protocol.
- Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
- Investigational agents other than atezolizumab.
- Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
- Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg IV with chemotherapy to prevent nausea is allowed.
- RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.
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Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade =< 2. TURBT is not considered a major surgical procedure.
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Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions:
- Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea).
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.
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Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment.
- Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment.
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Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
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Patients must be >= 18 years of age
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Patient may or may not be radical cystectomy candidates.
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Absolute neutrophil count (ANC) >= 1,500/microliter (mcL) (within 28 days prior to randomization).
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Platelets >= 100,000/mcL (within 28 days prior to randomization).
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Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
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Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization).
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization).
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Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
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Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization.
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Patients must have Zubrod performance status =< 2.
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Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization.
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Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis.
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Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
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Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis.
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Patient must not have a history of active tuberculosis.
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If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization.
- 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.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
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Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
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No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
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Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. 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 protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months.
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Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug.
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Patients must be offered the opportunity to participate in specimen banking for future studies.
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Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC Bowel Assessment, and the EQ-5D-5L per protocol schedule of assessment.
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As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (RT, chemotherapy) Gemcitabine Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Biopsy of Bladder Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Computed Tomography Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Cystoscopy Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Magnetic Resonance Imaging Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Quality-of-Life Assessment Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Radiation Therapy Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Survey Administration Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Transurethral Resection of Bladder Tumor Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Atezolizumab Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Biopsy of Bladder Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Computed Tomography Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Cystoscopy Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Fluorouracil Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Magnetic Resonance Imaging Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Quality-of-Life Assessment Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Radiation Therapy Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Survey Administration Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Transurethral Resection of Bladder Tumor Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Cisplatin Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Fluorouracil Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm I (RT, chemotherapy) Mitomycin Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Cisplatin Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Gemcitabine Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5. Arm II (RT, chemotherapy, atezolizumab) Mitomycin Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.
- Primary Outcome Measures
Name Time Method Bladder intact event-free survival (BI-EFS) From the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years At each time point, futility will be evaluated, and in the latter two analyses, efficacy will also be evaluated as specified. The final BI-EFS intent-to-treat analysis will be conducted using a stratified logrank test stratifying on stratification factors, and testing treatment at the one-sided significance level of 0.022 to account for multiple interim testing. The hazard ratio (HR) will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. Results from an unstratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median BI-EFS for each treatment arm.
- Secondary Outcome Measures
Name Time Method Biopsy response At 18 weeks The Cochran-Mantel-Haenszel statistic will be used with modified ridit scores to evaluate the biopsy outcomes of complete response versus (vs.) down-staging vs. no response for the two treatment arms.
Cancer-specific survival From date of randomization to date of death due to bladder cancer, assessed up to 5 years Modified bladder intact event-free survival (mBI-EFS) From date of randomization to the first documentation of a mBI-EFS event, assessed within 90 days Analysis of modified BI-EFS, i.e., a sensitivity analysis of BI-EFS, where bladder cancer event is defined as histologically proven presence of muscle invasive bladder cancer, clinical evidence of nodal or metastatic disease, radical cystectomy, or death within 90 days of receiving protocol specified treatment, will also be conducted.
Overall survival (OS) From date of randomization to death from any cause, assessed up to 5 years Will be estimated using Kaplan-Meier methodology for each treatment arm. Will be analyzed using a similar method as for BI-EFS.
Complete response duration From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed at 18 weeks For the subset of patients who achieve a complete response during the week 18 biopsy window, complete response duration is defined from the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause. Will be analyzed using a similar method as for BI-EFS.
Progression-free survival From date of randomization to first radiologic or histologic evidence of local progression, nodal or distant metastasis, or death due to any cause, assessed up to 5 years Will be estimated using Kaplan-Meier methodology for each treatment arm. Will be analyzed using a similar method as for BI-EFS.
Metastasis-free survival From date of randomization to first radiologic or histologic evidence of metastatic disease or death due to any cause, assessed up to 5 years Will be estimated using Kaplan-Meier methodology for each treatment arm. Will be analyzed using a similar method as for BI-EFS.
Quality of life Baseline up to 5 years Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ)-C30. Will be examined using linear mixed models with patient considered as the random effect. The baseline physical function score and the stratification factors will be included in the regression model as adjustment covariates.
Trial Locations
- Locations (367)
Aurora Cancer Care-Grafton
🇺🇸Grafton, Wisconsin, United States
Bellin Memorial Hospital
🇺🇸Green Bay, Wisconsin, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Mercy Cancer Center - Carmichael
🇺🇸Carmichael, California, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Mercy Cancer Center - Elk Grove
🇺🇸Elk Grove, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Los Angeles General Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Fremont - Rideout Cancer Center
🇺🇸Marysville, California, United States
Mercy Cancer Center - Sacramento
🇺🇸Sacramento, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Elmhurst Memorial Hospital
🇺🇸Elmhurst, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
Advocate South Suburban Hospital
🇺🇸Hazel Crest, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
🇺🇸Clive, Iowa, United States
Greater Regional Medical Center
🇺🇸Creston, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸West Des Moines, Iowa, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
Ascension Via Christi Hospitals Wichita
🇺🇸Wichita, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Sarasota Memorial Health Care Center at University Parkway
🇺🇸Sarasota, Florida, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Nebraska Medicine-Bellevue
🇺🇸Bellevue, Nebraska, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Nebraska Medicine-Village Pointe
🇺🇸Omaha, Nebraska, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Town Center
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Trinity Health Medical Center - Brighton
🇺🇸Brighton, Michigan, United States
University of Michigan - Brighton Center for Specialty Care
🇺🇸Brighton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸Canton, Michigan, United States
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Michigan Healthcare Professionals Clarkston
🇺🇸Clarkston, Michigan, United States
Corewell Health Dearborn Hospital
🇺🇸Dearborn, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Health Saint John Hospital
🇺🇸Detroit, Michigan, United States
Michigan Healthcare Professionals Farmington
🇺🇸Farmington Hills, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Corewell Health Farmington Hills Hospital
🇺🇸Farmington Hills, Michigan, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
ECU Health Oncology Richlands
🇺🇸Richlands, North Carolina, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
UPMC Hillman Cancer Center in Coraopolis
🇺🇸Moon, Pennsylvania, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Michael E DeBakey VA Medical Center
🇺🇸Houston, Texas, United States
UT Southwestern Clinical Center at Richardson/Plano
🇺🇸Richardson, Texas, United States
Dartmouth Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
Augusta Health Center for Cancer and Blood Disorders
🇺🇸Fishersville, Virginia, United States
MultiCare Auburn Medical Center
🇺🇸Auburn, Washington, United States
MultiCare Gig Harbor Medical Park
🇺🇸Gig Harbor, Washington, United States
FHCC at EvergreenHealth
🇺🇸Kirkland, Washington, United States
MultiCare Good Samaritan Hospital
🇺🇸Puyallup, Washington, United States
Valley Medical Center
🇺🇸Renton, Washington, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Vince Lombardi Cancer Clinic-Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Aspirus Cancer Care - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aurora Cancer Care-Milwaukee West
🇺🇸Wauwatosa, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸West Allis, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Mercy Cancer Center - Rocklin
🇺🇸Rocklin, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Pacific Central Coast Health Center-San Luis Obispo
🇺🇸San Luis Obispo, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
Woodland Memorial Hospital
🇺🇸Woodland, California, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers-Boulder
🇺🇸Boulder, Colorado, United States
UCHealth Memorial Hospital Central
🇺🇸Colorado Springs, Colorado, United States
Memorial Hospital North
🇺🇸Colorado Springs, Colorado, United States
Shaw Cancer Center
🇺🇸Edwards, Colorado, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
Cancer Care and Hematology-Fort Collins
🇺🇸Fort Collins, Colorado, United States
Banner North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
UCHealth Greeley Hospital
🇺🇸Greeley, Colorado, United States
Medical Center of the Rockies
🇺🇸Loveland, Colorado, United States
Banner McKee Medical Center
🇺🇸Loveland, Colorado, United States
Smilow Cancer Hospital Care Center at Greenwich
🇺🇸Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
🇺🇸Guilford, Connecticut, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Midstate Medical Center
🇺🇸Meriden, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
🇺🇸North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
🇺🇸Waterford, Connecticut, United States
Beebe South Coastal Health Campus
🇺🇸Millville, Delaware, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Mount Sinai Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Sarasota Memorial Hospital-Venice
🇺🇸N. Venice, Florida, United States
Florida Cancer Specialists - Sarasota
🇺🇸Sarasota, Florida, United States
Florida Cancer Specialists - Sarasota Downtown
🇺🇸Sarasota, Florida, United States
First Physicians Group - Urology Robotic and Minimally Invasive Surgery
🇺🇸Sarasota, Florida, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
CTCA at Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
Hawaii Cancer Care - Westridge
🇺🇸'Aiea, Hawaii, United States
Pali Momi Medical Center
🇺🇸'Aiea, Hawaii, United States
The Cancer Center of Hawaii-Pali Momi
🇺🇸'Aiea, Hawaii, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Cenrer - POB I
🇺🇸Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Straub Clinic and Hospital
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸Honolulu, Hawaii, United States
The Cancer Center of Hawaii-Liliha
🇺🇸Honolulu, Hawaii, United States
Advocate Good Shepherd Hospital
🇺🇸Barrington, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Advocate Illinois Masonic Medical Center
🇺🇸Chicago, Illinois, United States
AMG Crystal Lake - Oncology
🇺🇸Crystal Lake, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Advocate Good Samaritan Hospital
🇺🇸Downers Grove, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Advocate Sherman Hospital
🇺🇸Elgin, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
🇺🇸Highland Park, Illinois, United States
Edward Hines Jr VA Hospital
🇺🇸Hines, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
AMG Libertyville - Oncology
🇺🇸Libertyville, Illinois, United States
Condell Memorial Hospital
🇺🇸Libertyville, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸Naperville, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Community Cancer Center East
🇺🇸Indianapolis, Indiana, United States
Community Cancer Center South
🇺🇸Indianapolis, Indiana, United States
Community Cancer Center North
🇺🇸Indianapolis, Indiana, United States
Reid Health
🇺🇸Richmond, Indiana, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸Louisville, Kentucky, United States
Baptist Health Louisville
🇺🇸Louisville, Kentucky, United States
Louisiana Hematology Oncology Associates LLC
🇺🇸Baton Rouge, Louisiana, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
East Jefferson General Hospital
🇺🇸Metairie, Louisiana, United States
LSU Healthcare Network / Metairie Multi-Specialty Clinic
🇺🇸Metairie, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
MaineHealth Coastal Cancer Treatment Center
🇺🇸Bath, Maine, United States
MaineHealth Waldo Hospital
🇺🇸Belfast, Maine, United States
MaineHealth Maine Medical Center - Biddeford
🇺🇸Biddeford, Maine, United States
MaineHealth Stephens Hospital
🇺🇸Norway, Maine, United States
MaineHealth Maine Medical Center - Portland
🇺🇸Portland, Maine, United States
Penobscot Bay Medical Center
🇺🇸Rockport, Maine, United States
MaineHealth Cancer Care and IV Therapy - Sanford
🇺🇸Sanford, Maine, United States
MaineHealth Cancer Care Center of York County
🇺🇸Sanford, Maine, United States
MaineHealth Maine Medical Center- Scarborough
🇺🇸Scarborough, Maine, United States
MaineHealth Cancer Care and IV Therapy - South Portland
🇺🇸South Portland, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Lowell General Hospital
🇺🇸Lowell, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Henry Ford Saint John Hospital - Macomb Medical
🇺🇸Macomb, Michigan, United States
Michigan Healthcare Professionals Madison Heights
🇺🇸Madison Heights, Michigan, United States
Michigan Healthcare Professionals Pontiac
🇺🇸Pontiac, Michigan, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
🇺🇸Pontiac, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸Saginaw, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Michigan Healthcare Professionals Troy
🇺🇸Troy, Michigan, United States
Henry Ford Health Warren Hospital
🇺🇸Warren, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Dayton Physician LLC - Englewood
🇺🇸Dayton, Ohio, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸Saint Cloud, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Parkland Health Center-Bonne Terre
🇺🇸Bonne Terre, Missouri, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸Voorhees, New Jersey, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Highland Hospital
🇺🇸Rochester, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Phelps Memorial Hospital Center
🇺🇸Sleepy Hollow, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Good Samaritan University Hospital
🇺🇸West Islip, New York, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
ECU Health Oncology Kenansville
🇺🇸Kenansville, North Carolina, United States
ECU Health Oncology Kinston
🇺🇸Kinston, North Carolina, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
UPMC Altoona
🇺🇸Altoona, Pennsylvania, United States
UPMC-Heritage Valley Health System Beaver
🇺🇸Beaver, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Carlisle Regional Cancer Center
🇺🇸Carlisle, Pennsylvania, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
UPMC Hillman Cancer Center Erie
🇺🇸Erie, Pennsylvania, United States
UPMC Cancer Center at UPMC Horizon
🇺🇸Farrell, Pennsylvania, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
🇺🇸Greensburg, Pennsylvania, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
🇺🇸Harrisburg, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
🇺🇸Johnstown, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
UPMC Cancer Center at UPMC McKeesport
🇺🇸McKeesport, Pennsylvania, United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
🇺🇸Mechanicsburg, Pennsylvania, United States
UPMC Cancer Center - Monroeville
🇺🇸Monroeville, Pennsylvania, United States
Arnold Palmer Cancer Center Medical Oncology Norwin
🇺🇸N. Huntingdon, Pennsylvania, United States
UPMC Hillman Cancer Center - New Castle
🇺🇸New Castle, Pennsylvania, United States
UPMC-Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Saint Margaret
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Passavant Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Saint Clair Hospital Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Cancer Center at UPMC Northwest
🇺🇸Seneca, Pennsylvania, United States
UPMC Uniontown Hospital Radiation Oncology
🇺🇸Uniontown, Pennsylvania, United States
UPMC Washington Hospital Radiation Oncology
🇺🇸Washington, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
UPMC Memorial
🇺🇸York, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Carolina Regional Cancer Center
🇺🇸Myrtle Beach, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Aurora Cancer Care-Racine
🇺🇸Racine, Wisconsin, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Saint Michael Cancer Center
🇺🇸Silverdale, Washington, United States
MultiCare Tacoma General Hospital
🇺🇸Tacoma, Washington, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Ascension Saint Elizabeth Hospital
🇺🇸Appleton, Wisconsin, United States
Northwest Wisconsin Cancer Center
🇺🇸Ashland, Wisconsin, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸Burlington, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Mayo Clinic Health System-Eau Claire Clinic
🇺🇸Eau Claire, Wisconsin, United States
Aurora Health Care Germantown Health Center
🇺🇸Germantown, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸Green Bay, Wisconsin, United States
Aurora Cancer Care-Kenosha South
🇺🇸Kenosha, Wisconsin, United States
Mayo Clinic Health System-Franciscan Healthcare
🇺🇸La Crosse, Wisconsin, United States
Aurora Bay Area Medical Group-Marinette
🇺🇸Marinette, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Aspirus Medford Hospital
🇺🇸Medford, Wisconsin, United States
Aurora Cancer Care-Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Aurora Sinai Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Ascension Mercy Hospital
🇺🇸Oshkosh, Wisconsin, United States
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸Oshkosh, Wisconsin, United States
Ascension All Saints Hospital
🇺🇸Racine, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
Vince Lombardi Cancer Clinic-Two Rivers
🇺🇸Two Rivers, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States