Susan Kreissman

Overview:

The emphasis of Dr Kreissman's clinical research involves the study of childhood neuroblastoma. Neuroblastoma is the most common extracranial solid tumor of childhood and this disease has a diverse clinical phenotype and prognosis. Dr Kreissman has developed, written, and served as national protocol chairman for 2 clinical trials designed to improve outcome for children with the high risk form of this disease through the Children's Oncology Group (COG). Results of this protocol have been published " A Randomized Study of Purged Versus Unpurged Peripheral Blood Stem Cell Transplant Following Dose Intensive Induction Therapy for High Risk Neuroblastoma" and established the new standard of using unpurged PBSC to support autologous transplant in high risk neuroblastoma. Dr. Kreissman also serves as a member of the Neuroblastoma committees for COG. She is involved in designing and implimenting additional new protocols for the treatment of neuroblastoma.

Positions:

Professor of Pediatrics

Pediatrics, Hematology-Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1985

Icahn School of Medicine at Mount Sinai

Intern, Pediatrics

Children's Hospital Boston

Resident, Pediatrics

Children's Hospital Boston

Clinical Fellow, Pediatric Hematology/Oncology, Pediatrics

Children's Hospital Boston

Research Fellow, Pediatric Hematology/Oncology, Pediatrics

Children's Hospital Boston

Grants:

Stroma Biology Identifies Heparin as a Differentiating Agent in Neuroblastoma

Administered By
Medicine, Medical Oncology
Awarded By
Alex's Lemonade Stand
Role
Co Investigator
Start Date
End Date

COG Work Order AAML: 1031--Millennium Pharmaceuticals, Inc.

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

COG Work Order: AALL1131: Ph III Clofarabine in High Risk B ALL

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

NCI Community Oncology Research Program (NCORP) Research Base Grant

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

COG WORK ORDER: (PROJECT: PEDIATRIC MATCH (APEC1621SC) PCR - COG FOUNDATION

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

Publications:

More Than Meets the Eye? A Cautionary Tale of Malignant Ectomesenchymoma Treated as Low-risk Orbital Rhabdomyosarcoma.

Malignant ectomesenchymoma (MEM) is a rare multiphenotypic tumor comprised of mesenchymal and neuroectodermal components. MEM is typically diagnosed in infants and younger children and outcomes are variable. The current approach for treating MEM includes targeting the more aggressive mesenchymal component of the tumor, which is often rhabdomyosarcoma. Here, we describe a case of an orbital tumor initially diagnosed and treated as low-risk rhabdomyosarcoma. Local failure prompting a second biopsy revealed neuronal differentiation consistent with a diagnosis of MEM. Intensifying therapy and local radiotherapy led to a long-term cure. This case offers a cautionary tale that while outcomes for MEM were similar to matched rhabdomyosarcoma cohorts when treated on conventional Intergroup Rhabdomyosarcoma Study Group (IRSG) III/IV protocols, treating MEM using a decreased intensity low-risk rhabdomyosarcoma regimen may not be sufficient.
Authors
Rashid, T; Bagatell, R; Pawel, B; Bentley, RC; Kreissman, SG; Deel, MD
MLA Citation
Rashid, Tooba, et al. “More Than Meets the Eye? A Cautionary Tale of Malignant Ectomesenchymoma Treated as Low-risk Orbital Rhabdomyosarcoma.J Pediatr Hematol Oncol, vol. 43, no. 6, Aug. 2021, pp. e854–58. Pubmed, doi:10.1097/MPH.0000000000001901.
URI
https://scholars.duke.edu/individual/pub1454086
PMID
32769567
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
43
Published Date
Start Page
e854
End Page
e858
DOI
10.1097/MPH.0000000000001901

Integration of cancer registry and electronic health record data to construct a childhood cancer survivorship cohort, facilitate risk stratification for late effects, and assess appropriate follow-up care.

BACKGROUND: This retrospective study harnessed an institutional cancer registry to construct a childhood cancer survivorship cohort, integrate electronic health record (EHR) and geospatial data to stratify survivors based on late-effect risk, analyze follow-up care patterns, and determine factors associated with suboptimal follow-up care. PROCEDURE: The survivorship cohort included patients ≤18 years of age reported to the institutional cancer registry between January 1, 1994 and November 30, 2012. International Classification of Diseases for Oncology, third revision (ICD-O-3) coding and treatment exposures facilitated risk stratification of survivors. The EHR was linked to the cancer registry based on medical record number (MRN) to extract clinic visits. RESULTS: Five hundred and ninety pediatric hematology-oncology (PHO) and 275 pediatric neuro-oncology (PNO) survivors were included in the final analytic cohort. Two hundred and eight-two survivors (32.6%) were not seen in any oncology-related subspecialty clinic at Duke 5-7 years after initial diagnosis. Factors associated with follow-up included age (p = .008), diagnosis (p < .001), race/ethnicity (p = .010), late-effect risk strata (p = .001), distance to treatment center (p < .0001), and area deprivation index (ADI) (p = .011). Multivariable logistic modeling attenuated the association for high-risk (OR 1.72; 95% CI 0.805, 3.66) and intermediate-risk (OR 1.23, 95% CI 0.644, 2.36) survivors compared to survivors at low risk of late effects among the PHO cohort. PNO survivors at high risk for late effects were more likely to follow up (adjusted OR 3.66; 95% CI 1.76, 7.61). CONCLUSIONS: Nearly a third of survivors received suboptimal follow-up care. This study provides a reproducible model to integrate cancer registry and EHR data to construct risk-stratified survivorship cohorts to assess follow-up care.
Authors
Noyd, DH; Neely, NB; Schroeder, KM; Lantos, PM; Power, S; Kreissman, SG; Oeffinger, KC
URI
https://scholars.duke.edu/individual/pub1476847
PMID
33742534
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
68
Published Date
Start Page
e29014
DOI
10.1002/pbc.29014

Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children's Oncology Group ANBL0532 Study.

PURPOSE: A primary objective of the Children's Oncology Group (COG) ANBL0532 phase III study was to assess the effect of increasing local dose of radiation to a residual primary tumor on the cumulative incidence of local progression (CILP) in patients with high-risk neuroblastoma. PATIENTS AND METHODS: Newly diagnosed patients with high-risk neuroblastoma were randomly assigned or assigned to receive single or tandem autologous stem-cell transplantation (SCT) after induction chemotherapy. Local control consisted of surgical resection during induction chemotherapy and radiotherapy after last SCT. Patients received 21.6 Gy to the preoperative primary tumor volume. For patients with incomplete surgical resection, an additional boost of 14.4 Gy was delivered to the gross residual tumor, for a total dose of 36 Gy. CILP (primary end point) and event-free (EFS) and overall survival (OS; secondary end points) were compared with the COG A3973 historical cohort, in which all patients received single SCT and 21.6 Gy without a boost. RESULTS: For all patients in ANBL0532 receiving radiotherapy (n = 323), 5-year CILP, EFS, and OS rates were 11.2% ± 1.8%, 56.2% ± 3.4%, and 68.4% ± 3.2% compared with 7.1% ± 1.4% (P = .0590), 47.0% ± 3.5% (P = .0090), and 57.4% ± 3.5% (P = .0088) for all patients in A3973 receiving radiotherapy (n = 328), respectively. Five-year CILP, EFS, and OS rates for patients in A3973 with incomplete resection and radiotherapy (n = 47) were 10.6% ± 4.6%, 48.9% ± 10.1%, and 56.9% ± 10.0%, respectively. In comparison, 5-year CILP, EFS, and OS rates for patients in ANBL0532 who were randomly assigned or assigned to single SCT and received boost radiotherapy (n = 74) were 16.3% ± 4.3% (P = .4126), 50.9% ± 7.0% (P = .5084), and 68.1% ± 6.7% (P = .2835), respectively. CONCLUSION: Boost radiotherapy to gross residual tumor present at the end of induction did not significantly improve 5-year CILP. These results highlight the need for new strategies to decrease the risk of locoregional failure.
Authors
Liu, KX; Naranjo, A; Zhang, FF; DuBois, SG; Braunstein, SE; Voss, SD; Khanna, G; London, WB; Doski, JJ; Geiger, JD; Kreissman, SG; Grupp, SA; Diller, LR; Park, JR; Haas-Kogan, DA
MLA Citation
URI
https://scholars.duke.edu/individual/pub1448417
PMID
32530765
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
38
Published Date
Start Page
2741
End Page
2752
DOI
10.1200/JCO.19.03316

Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial.

Importance: Induction chemotherapy followed by high-dose therapy with autologous stem cell transplant and subsequent antidisialoganglioside antibody immunotherapy is standard of care for patients with high-risk neuroblastoma, but survival rate among these patients remains low. Objective: To determine if tandem autologous transplant improves event-free survival (EFS) compared with single transplant. Design, Setting, and Participants: Patients were enrolled in this randomized clinical trial from November 2007 to February 2012 at 142 Children's Oncology Group centers in the United States, Canada, Switzerland, Australia, and New Zealand. A total of 652 eligible patients aged 30 years or younger with protocol-defined high-risk neuroblastoma were enrolled and 355 were randomized. The final date of follow-up was June 29, 2017, and the data analyses cut-off date was June 30, 2017. Interventions: Patients were randomized to receive tandem transplant with thiotepa/cyclophosphamide followed by dose-reduced carboplatin/etoposide/melphalan (n = 176) or single transplant with carboplatin/etoposide/melphalan (n = 179). Main Outcomes and Measures: The primary outcome was EFS from randomization to the occurrence of the first event (relapse, progression, secondary malignancy, or death from any cause). The study was designed to test the 1-sided hypothesis of superiority of tandem transplant compared with single transplant. Results: Among the 652 eligible patients enrolled, 297 did not undergo randomization because they were nonrandomly assigned (n = 27), ineligible for randomization (n = 62), had no therapy (n = 1), or because of physician/parent preference (n = 207). Among 355 patients randomized (median diagnosis age, 36.1 months; 152 [42.8%] female), 297 patients (83.7%) completed the study and 21 (5.9%) were lost to follow-up after completing protocol therapy. Three-year EFS from the time of randomization was 61.6% (95% CI, 54.3%-68.9%) in the tandem transplant group and 48.4% (95% CI, 41.0%-55.7%) in the single transplant group (1-sided log-rank P=.006). The median (range) duration of follow-up after randomization for 181 patients without an event was 5.6 (0.6-8.9) years. The most common significant toxicities following tandem vs single transplant were mucosal (11.7% vs 15.4%) and infectious (17.9% vs 18.3%). Conclusions and Relevance: Among patients aged 30 years or younger with high-risk neuroblastoma, tandem transplant resulted in a significantly better EFS than single transplant. However, because of the low randomization rate, the findings may not be representative of all patients with high-risk neuroblastoma. Trial Registration: ClinicalTrials.gov Identifier: NCT00567567.
Authors
Park, JR; Kreissman, SG; London, WB; Naranjo, A; Cohn, SL; Hogarty, MD; Tenney, SC; Haas-Kogan, D; Shaw, PJ; Kraveka, JM; Roberts, SS; Geiger, JD; Doski, JJ; Voss, SD; Maris, JM; Grupp, SA; Diller, L
MLA Citation
Park, Julie R., et al. “Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial.Jama, vol. 322, no. 8, Aug. 2019, pp. 746–55. Pubmed, doi:10.1001/jama.2019.11642.
URI
https://scholars.duke.edu/individual/pub1406381
PMID
31454045
Source
pubmed
Published In
Jama
Volume
322
Published Date
Start Page
746
End Page
755
DOI
10.1001/jama.2019.11642

Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial.

BACKGROUND: Paediatric low-grade glioma is the most common CNS tumour of childhood. Although overall survival is good, disease often recurs. No single universally accepted treatment exists for these patients; however, standard cytotoxic chemotherapies are generally used. We aimed to assess the activity of selumetinib, a MEK1/2 inhibitor, in these patients. METHODS: The Pediatric Brain Tumor Consortium performed a multicentre, phase 2 study in patients with paediatric low-grade glioma in 11 hospitals in the USA. Patients aged 3-21 years with a Lansky or Karnofsky performance score greater than 60 and the presence of recurrent, refractory, or progressive paediatric low-grade glioma after at least one standard therapy were eligible for inclusion. Patients were assigned to six unique strata according to histology, tumour location, NF1 status, and BRAF aberration status; herein, we report the results of strata 1 and 3. Stratum 1 comprised patients with WHO grade I pilocytic astrocytoma harbouring either one of the two most common BRAF aberrations (KIAA1549-BRAF fusion or the BRAFV600E [Val600Glu] mutation). Stratum 3 comprised patients with any neurofibromatosis type 1 (NF1)-associated paediatric low-grade glioma (WHO grades I and II). Selumetinib was provided as capsules given orally at the recommended phase 2 dose of 25 mg/m2 twice daily in 28-day courses for up to 26 courses. The primary endpoint was the proportion of patients with a stratum-specific objective response (partial response or complete response), as assessed by the local site and sustained for at least 8 weeks. All responses were reviewed centrally. All eligible patients who initiated treatment were evaluable for the activity and toxicity analyses. Although the trial is ongoing in other strata, enrolment and planned follow-up is complete for strata 1 and 3. This trial is registered with ClinicalTrials.gov, number NCT01089101. FINDINGS: Between July 25, 2013, and June 12, 2015, 25 eligible and evaluable patients were accrued to stratum 1, and between Aug 28, 2013, and June 25, 2015, 25 eligible and evaluable patients were accrued to stratum 3. In stratum 1, nine (36% [95% CI 18-57]) of 25 patients achieved a sustained partial response. The median follow-up for the 11 patients who had not had a progression event by Aug 9, 2018, was 36·40 months (IQR 21·72-45·59). In stratum 3, ten (40% [21-61]) of 25 patients achieved a sustained partial response; median follow-up was 48·60 months (IQR 39·14-51·31) for the 17 patients without a progression event by Aug 9, 2018. The most frequent grade 3 or worse adverse events were elevated creatine phosphokinase (five [10%]) and maculopapular rash (five [10%]). No treatment-realted deaths were reported. INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma. These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1. FUNDING: National Cancer Institute Cancer Therapy Evaluation Program, the American Lebanese Syrian Associated Charities, and AstraZeneca.
Authors
Fangusaro, J; Onar-Thomas, A; Young Poussaint, T; Wu, S; Ligon, AH; Lindeman, N; Banerjee, A; Packer, RJ; Kilburn, LB; Goldman, S; Pollack, IF; Qaddoumi, I; Jakacki, RI; Fisher, PG; Dhall, G; Baxter, P; Kreissman, SG; Stewart, CF; Jones, DTW; Pfister, SM; Vezina, G; Stern, JS; Panigrahy, A; Patay, Z; Tamrazi, B; Jones, JY; Haque, SS; Enterline, DS; Cha, S; Fisher, MJ; Doyle, LA; Smith, M; Dunkel, IJ; Fouladi, M
MLA Citation
Fangusaro, Jason, et al. “Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial.Lancet Oncol, vol. 20, no. 7, July 2019, pp. 1011–22. Pubmed, doi:10.1016/S1470-2045(19)30277-3.
URI
https://scholars.duke.edu/individual/pub1387958
PMID
31151904
Source
pubmed
Published In
Lancet Oncol
Volume
20
Published Date
Start Page
1011
End Page
1022
DOI
10.1016/S1470-2045(19)30277-3