Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT
- Conditions
- Central Nervous System Tumor, Pediatric
- Interventions
- Biological: filgrastimRadiation: radiation therapy
- Registration Number
- NCT00084838
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumors.
- Detailed Description
OBJECTIVES:
Primary
* Determine the efficacy of intensive systemic and intrathecal chemotherapy and radiotherapy, in terms of medial survival, in children with newly diagnosed central nervous system atypical teratoid/rhabdoid tumors in comparison with historical outcomes from prior trials.
Secondary
* Determine the toxicity profile and tolerability of this regimen in these patients.
* Determine the chemosensitivity of these patients' tumors by Magnetic Resonance Imaging (MRI) after an attempt at maximum surgical resection after 2 courses of this regimen.
* Determine the predictive value of the INI-1 gene mutation in determining prognosis by comparing tumor samples from patients with vs without this mutation treated with this regimen.
STATISTICAL DESIGN: This was a single arm design evaluating median overall survival. The chosen historical control estimate of 7 months was based on 2 large multi-institutional studies in a similar setting and the alternative of 20.5 months based on a DFCI pilot study. There was 90% power to detect this improvement assuming 1-sided 0.10 alpha and 17 eligible patients. Sample size (n=20 patients) was inflated for expected 10-15% ineligible rate.
TREATMENT: Induction chemotherapy was required to be initiated within 50 days of the most definitive surgery.
* Central Nervous System (CNS)/intrathecal therapy: All patients with M0 disease receive triple intrathecal (IT) chemotherapy comprising methotrexate (MTX), cytarabine, and hydrocortisone on day 1 of weeks 1, 2, 4, 7, 13, 19, 27, 33, 39, 45, and 51 followed by oral or intravenous (IV) leucovorin calcium given 24 hours after each MTX dose. Patients with initially positive cerebrospinal fluid (CSF) cytology (M+) receive triple IT chemotherapy weekly until 2 consecutive CSF samples are negative for malignant cells.
* Pre-irradiation induction therapy (weeks 1-6): Patients receive vincristine IV on day 1 of weeks 1-6; cisplatin IV over 8 hours on day 1 and doxorubicin IV continuously over 48 hours beginning on day 2 of weeks 1 and 4; cyclophosphamide IV continuously over 72 hours beginning on day 2 of week 1; etoposide IV over 1 hour on days 1-3 of week 4; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 of week 1 and day 4 of week 4 and continuing until blood counts recover.
* Induction chemoradiotherapy (weeks 7-12): Patients receive vincristine IV on day 1 of weeks 7-12; cisplatin IV over 8 hours on day 1, cyclophosphamide IV over 1 hour on day 2, etoposide IV over 1 hour on days 1-3 of weeks 7 and 10; and granulocyte-colony stimulating factor (G-CSF) subcutaneous (SC) daily beginning on day 4 of weeks 7 and 10 and continuing until blood counts recover. Patients with M0 disease and patients under 3 years of age with M+ disease undergo radiotherapy to the primary tumor daily on weeks 7-12. Patients 3 years of age and over with M+ disease undergo craniospinal irradiation (CSI) daily on weeks 7-12 until negative cerebral spinal fluid (CSF) cytology is achieved.
* Post-radiation induction therapy (weeks 13-18): Patients receive vincristine IV on day 1 of weeks 13 and 16; doxorubicin and cyclophosphamide as in pre-irradiation induction therapy beginning on day 1 of week 13; cyclophosphamide IV over 1 hour on days 1-3 of week 16; dactinomycin IV on days 1-5 of week 16; and G-CSF SC daily beginning on day 6 of weeks 13 and 16 and continuing until blood counts recover.
* Maintenance chemotherapy (weeks 19-42): Patients receive vincristine IV on day 1 of weeks 27, 33, and 39 and days 1 and 5 of weeks 30, 36, and 42; doxorubicin and cyclophosphamide as in pre-irradiation induction beginning on day 1 of weeks 27 and 33; doxorubicin IV over 15 minutes and dexrazoxane (DX) IV over 15 minutes on days 1 and 2 of week 39; cyclophosphamide IV over 1 hour on days 1-3 of weeks 30, 36, 39, and 42; dactinomycin IV on days 1-5 of weeks 30, 36, and 42 and on day 1 of weeks 19 and 23; oral temozolomide on days 1-5 of weeks 19 and 23; and G-CSF SC daily beginning on day 6 of weeks 19, 23, 30, 36, and 42, day 5 of weeks 27 and 33, and day 4 of week 39 and continuing until blood counts recover.
* Doxorubicin continuation therapy (for patients not receiving CSI and mediastinal radiotherapy)(weeks 45-51): Patients receive vincristine IV on day 1 of weeks 45, 48, and 51 and day 5 of week 48; doxorubicin IV over 15 minutes and DX IV over 15 minutes on days 1 and 2 of weeks 45 and 51; cyclophosphamide IV over 1 hour on days 1-3 of weeks 45, 48, and 51; dactinomycin IV on days 1-5 of week 48; and G-CSF SC daily beginning on day 4 of weeks 45 and 51 and day 6 of week 48 and continuing until blood counts recover.
* Non-doxorubicin continuation therapy (for patients receiving CSI or mediastinal radiotherapy)(weeks 45-51): Patients receive cyclophosphamide and G-CSF as in doxorubicin continuation therapy; vincristine IV on days 1 and 5 of weeks 45, 48, and 51; and dactinomycin IV on days 1-5 of weeks 45, 48, and 51.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) dexrazoxane hydrochloride Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) leucovorin calcium Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) vincristine sulfate Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) filgrastim Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) therapeutic hydrocortisone Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) radiation therapy Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) Dactinomycin Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) cyclophosphamide Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) cisplatin Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) cytarabine Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) doxorubicin hydrochloride Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) etoposide Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) methotrexate Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III) temozolomide Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51) Induction Chemotherapy: CT backbone of the IRS-III regimen \[vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)\] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT. Radiation Therapy: Pts w/ M0 dz OR M+ dz aged \<3y received focal RT (3D conformal or intensity-modulated delivery). Pts \>3y w/ M+ dz rcvd craniospinal irradiation. Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.
- Primary Outcome Measures
Name Time Method 2-yr Overall Survival Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months. Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up.
- Secondary Outcome Measures
Name Time Method Pre-Radiation Therapy Chemotherapeutic Response Assessed at study entry and pre-RT/post-CT at week 7. Response pre-RT/post-CT was defined as follows with overall response defined as achieving PR or CR.
Complete Response (CR): Complete resolution of all initially demonstrable tumor on MRI or CT evaluation w/o appearance of any new areas of disease; negative CSF cytology. Partial Response (PR): \>/= 50% decrease in the sum of the products of the maximum perpendicular diameters of the tumor (sum LD) relative to baseline w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Stable Disease (SD): \<50% decrease in the sum LD w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Progressive Disease (PD): \>/= 25% increase in the sum LD relative to baseline, or the appearance of any new areas of disease or appearance of positive cytology after two consecutive negative samples.
Trial Locations
- Locations (12)
Stanford Cancer Center
🇺🇸Stanford, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
🇺🇸Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States