Suzanne Wolden - Academia.edu (original) (raw)

Papers by Suzanne Wolden

Neuro-Oncology, 2020

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiothera... more Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiotherapy (RT) is integral to LC treatment, and proton craniospinal irradiation (CSI) may make RT more effective by targeting the entire central nervous system (CNS) compartment. We evaluated outcomes in patients treated with proton CSI for LC. We identified 56 patients treated with proton CSI for LC between 2018 and 2020 at our institution. Data on patient demographics, disease and treatment history, cerebrospinal fluid circulating tumor cells (CSF CTCs), and gene alterations were collected. Kaplan Meier analysis and Cox regression models were used to compare correlates with CNS time to progression (TTP), CNS progression-free survival (PFS) and overall survival (OS). Most patients had non-small cell lung cancer (NSCLC, n=27, 48%) or breast cancer (n=21, 38%). The median age was 58 (30-77), and median KPS was 80 (60-90). The median RT dose was 30Gy (25-36). The median follow-up was 12 months (1...

Journal of Adolescent and Young Adult Oncology

Neuro-Oncology, 2018

errors in VRT, LAT and AP directions were recorded by Exactrac® with Robotic® before radiotherapy... more errors in VRT, LAT and AP directions were recorded by Exactrac® with Robotic® before radiotherapy. RESULTS: The average of transmittance was 98.891455% in group 1 and 98.51455% in group 2. The setup errors in VRT, LAT and AP directions were (0.040 ± 0.055) mm, (0.040 ± 0.055) mm and (0.10 ± 0.07) mm in group 1, as compared with (0.160 ± 0.055) mm, (0.08 ± 0.11) mm and (0.10 ± 0.10) mm in group 2. 3D printed headrest reduced setup errors in VRT direction (P<0.05) with no significant difference in the other two directions (P>0.05). CONCLUSION: Compared with BRAINLAB® SRS standard headrest, 3D printed headrest for pediatric patients showed higher transmittance and reduces the setup errors in VRT direction.

Blood, 2016

Background: Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent mal... more Background: Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMN). Response-adapted treatment for HL may decrease the SMN risk by reducing therapy in patients who have a good initial response to treatment. The Children's Oncology Group Study AHOD0031, which enrolled patients from 2002 - 2009, evaluated the role of early treatment response in directing therapy for children and adolescents with intermediate-risk Hodgkin lymphoma. We report the incidence and risk factors for SMN among 1,711 eligible patients enrolled on AHOD0031. Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE...

In this manuscript we analyze a data set containing information on children with Hodgkin Lymphoma... more In this manuscript we analyze a data set containing information on children with Hodgkin Lymphoma (HL) enrolled on a clinical trial. Treatments received and survival status were collected together with other covariates such as demographics and clinical measurements. Our main task is to explore the potential of machine learning (ML) algorithms in a survival analysis context in order to improve over the Cox Proportional Hazard (CoxPH) model. We discuss the weaknesses of the CoxPH model we would like to improve upon and then we introduce multiple algorithms, from well-established ones to state-of-the-art models, that solve these issues. We then compare every model according to the concordance index and the brier score. Finally, we produce a series of recommendations, based on our experience, for practitioners that would like to benefit from the recent advances in artificial intelligence.

Practical Guides in Radiation Oncology

Pediatric Blood & Cancer, 2021

Radiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly app... more Radiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly applied in pediatric oncology. They are often used in the setting of reirradiation for recurrent or metastatic tumors. Reirradiation in children with recurrent tumors is complicated by the tolerance of critical organs and the potential risks for overall long‐term dose‐dependent complications. We review the current literature available in support of reirradiation and the use of radiosurgery and brachytherapy in pediatric patients.

International Journal of Radiation Oncology*Biology*Physics

Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk ... more Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure Patients aged 10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

Journal of Lipid Research

Blood

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs... more Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children’s Oncology Group study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1711 patients enrolled in AHOD0031. Patients were treated with 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved-field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to 2 additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow-up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% confidence interval [CI], 0.6-2.0). SMNs included 3 patients with acute myeloid leukemi...

Neuro-Oncology

Background Leptomeningeal metastases (LM) are associated with limited survival and treatment opti... more Background Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. Methods We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). Results We enrolled 24 patients between June 2018 and April 2019. Their median follow...

Blood

766 The challenge in treating children with Hodgkin lymphoma (HL) is to continue progress in its ... more 766 The challenge in treating children with Hodgkin lymphoma (HL) is to continue progress in its curability while diminishing the risk for toxic events that compromise quality of life and survival. This therapeutic Phase III trial for patients with intermediate risk HL was designed to meet these tandem goals. Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. All patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), at which point a response evaluation was performed. Rapid early (RER) versus slow early responder (SER) status was defined by CT imaging. All SER patients were randomized at the end of 2 cycles to an additional two cycles of ABVE-PC vs. 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA) followed by 2 additional cycles of ABVE-PC. All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of...

Blood

3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (H... more 3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. Background: Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this re...

Blood

Higher cGVHD, TRM and treatment failure following sibling donor unmanipulated allogeneic PBSCT co... more Higher cGVHD, TRM and treatment failure following sibling donor unmanipulated allogeneic PBSCT compared to BMT in children and adolescents has been reported by the IBMTR (Eapen M et al, J Clin Oncol, 2004). To determine the effect of T cell depletion (TCD) of PBSC on outcome for pediatric patients with AML or MDS, we reviewed our results with 49 patients (pts) with AML-1CR (n=18), AML-CR2 (n=11), MDS (n=10) and tAML/MDS (n=8/2) following allogeneic TCD-PBSCT transplanted between June 2003 and January 2015. Median age in this cohort was 13.9yrs (range 1.9 - 20.4) with 27 males and 19pts CMV seropositive at time of PBSCT. Donors were related HLA identical (14siblings, 1uncle), unrelated HLA 10/10 matched (n=14) or unrelated HLA mismatched (n=20: 9/10 n=12: 8/10 n=8). Cytoreduction consisted of a HFTBI containing regimen (n=14) with thiotepa and cyclophosphamide (n=12) or thiotepa and fludarabine (n=2). Alternatively, 35 pts received chemotherapy alone: BU/MEL/FLU (n=31) or other (n=4)...

Journal of Pediatric Hematology/Oncology

Cancer

Background: To evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) ... more Background: To evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: We analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan on the experimental arm. Individualized local control plans for children ≤24 months were allowed. Local failure (LF) on ARST0531 was compared to LF on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n=55), the 5-year cumulative incidence of LF was 13.4%; for group III alveolar RMS (n=141), 20.2%; and for group III embryonal RMS (n=228), 27.9% (p=0.03). Among patients with group III disease, LF did not differ by histology, site, nodal status, RT modality, or treatment arm. LF was worse for tumor size >5cm (32.3% vs 16.7%, p=0.001). Among patients with group III embryonal RMS, LF was higher on ARST0531 compared to D9803 (27.9% vs 19.4%, p=0.03). After excluding patients ≤24 months or patients who did not receive radiation, LF remained significantly increased on ARST0531 (p=0.02). After adjusting for clinical prognostic factors, event-free and overall survival were worse on ARST0531 (p=0.004 and p=0.05). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 compared to D9803. The reason for this is unclear but could be due to the reduced cyclophosphamide dose on ARST0531.

International Journal of Radiation Oncology*Biology*Physics

Neuro-Oncology, 2020

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiothera... more Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiotherapy (RT) is integral to LC treatment, and proton craniospinal irradiation (CSI) may make RT more effective by targeting the entire central nervous system (CNS) compartment. We evaluated outcomes in patients treated with proton CSI for LC. We identified 56 patients treated with proton CSI for LC between 2018 and 2020 at our institution. Data on patient demographics, disease and treatment history, cerebrospinal fluid circulating tumor cells (CSF CTCs), and gene alterations were collected. Kaplan Meier analysis and Cox regression models were used to compare correlates with CNS time to progression (TTP), CNS progression-free survival (PFS) and overall survival (OS). Most patients had non-small cell lung cancer (NSCLC, n=27, 48%) or breast cancer (n=21, 38%). The median age was 58 (30-77), and median KPS was 80 (60-90). The median RT dose was 30Gy (25-36). The median follow-up was 12 months (1...

Journal of Adolescent and Young Adult Oncology

Neuro-Oncology, 2018

errors in VRT, LAT and AP directions were recorded by Exactrac® with Robotic® before radiotherapy... more errors in VRT, LAT and AP directions were recorded by Exactrac® with Robotic® before radiotherapy. RESULTS: The average of transmittance was 98.891455% in group 1 and 98.51455% in group 2. The setup errors in VRT, LAT and AP directions were (0.040 ± 0.055) mm, (0.040 ± 0.055) mm and (0.10 ± 0.07) mm in group 1, as compared with (0.160 ± 0.055) mm, (0.08 ± 0.11) mm and (0.10 ± 0.10) mm in group 2. 3D printed headrest reduced setup errors in VRT direction (P<0.05) with no significant difference in the other two directions (P>0.05). CONCLUSION: Compared with BRAINLAB® SRS standard headrest, 3D printed headrest for pediatric patients showed higher transmittance and reduces the setup errors in VRT direction.

Blood, 2016

Background: Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent mal... more Background: Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMN). Response-adapted treatment for HL may decrease the SMN risk by reducing therapy in patients who have a good initial response to treatment. The Children's Oncology Group Study AHOD0031, which enrolled patients from 2002 - 2009, evaluated the role of early treatment response in directing therapy for children and adolescents with intermediate-risk Hodgkin lymphoma. We report the incidence and risk factors for SMN among 1,711 eligible patients enrolled on AHOD0031. Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE...

In this manuscript we analyze a data set containing information on children with Hodgkin Lymphoma... more In this manuscript we analyze a data set containing information on children with Hodgkin Lymphoma (HL) enrolled on a clinical trial. Treatments received and survival status were collected together with other covariates such as demographics and clinical measurements. Our main task is to explore the potential of machine learning (ML) algorithms in a survival analysis context in order to improve over the Cox Proportional Hazard (CoxPH) model. We discuss the weaknesses of the CoxPH model we would like to improve upon and then we introduce multiple algorithms, from well-established ones to state-of-the-art models, that solve these issues. We then compare every model according to the concordance index and the brier score. Finally, we produce a series of recommendations, based on our experience, for practitioners that would like to benefit from the recent advances in artificial intelligence.

Practical Guides in Radiation Oncology

Pediatric Blood & Cancer, 2021

Radiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly app... more Radiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly applied in pediatric oncology. They are often used in the setting of reirradiation for recurrent or metastatic tumors. Reirradiation in children with recurrent tumors is complicated by the tolerance of critical organs and the potential risks for overall long‐term dose‐dependent complications. We review the current literature available in support of reirradiation and the use of radiosurgery and brachytherapy in pediatric patients.

International Journal of Radiation Oncology*Biology*Physics

Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk ... more Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure Patients aged 10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

Journal of Lipid Research

Blood

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs... more Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children’s Oncology Group study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1711 patients enrolled in AHOD0031. Patients were treated with 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved-field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to 2 additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow-up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% confidence interval [CI], 0.6-2.0). SMNs included 3 patients with acute myeloid leukemi...

Neuro-Oncology

Background Leptomeningeal metastases (LM) are associated with limited survival and treatment opti... more Background Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. Methods We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). Results We enrolled 24 patients between June 2018 and April 2019. Their median follow...

Blood

766 The challenge in treating children with Hodgkin lymphoma (HL) is to continue progress in its ... more 766 The challenge in treating children with Hodgkin lymphoma (HL) is to continue progress in its curability while diminishing the risk for toxic events that compromise quality of life and survival. This therapeutic Phase III trial for patients with intermediate risk HL was designed to meet these tandem goals. Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. All patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), at which point a response evaluation was performed. Rapid early (RER) versus slow early responder (SER) status was defined by CT imaging. All SER patients were randomized at the end of 2 cycles to an additional two cycles of ABVE-PC vs. 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA) followed by 2 additional cycles of ABVE-PC. All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of...

Blood

3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (H... more 3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. Background: Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this re...

Blood

Higher cGVHD, TRM and treatment failure following sibling donor unmanipulated allogeneic PBSCT co... more Higher cGVHD, TRM and treatment failure following sibling donor unmanipulated allogeneic PBSCT compared to BMT in children and adolescents has been reported by the IBMTR (Eapen M et al, J Clin Oncol, 2004). To determine the effect of T cell depletion (TCD) of PBSC on outcome for pediatric patients with AML or MDS, we reviewed our results with 49 patients (pts) with AML-1CR (n=18), AML-CR2 (n=11), MDS (n=10) and tAML/MDS (n=8/2) following allogeneic TCD-PBSCT transplanted between June 2003 and January 2015. Median age in this cohort was 13.9yrs (range 1.9 - 20.4) with 27 males and 19pts CMV seropositive at time of PBSCT. Donors were related HLA identical (14siblings, 1uncle), unrelated HLA 10/10 matched (n=14) or unrelated HLA mismatched (n=20: 9/10 n=12: 8/10 n=8). Cytoreduction consisted of a HFTBI containing regimen (n=14) with thiotepa and cyclophosphamide (n=12) or thiotepa and fludarabine (n=2). Alternatively, 35 pts received chemotherapy alone: BU/MEL/FLU (n=31) or other (n=4)...

Journal of Pediatric Hematology/Oncology

Cancer

Background: To evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) ... more Background: To evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: We analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan on the experimental arm. Individualized local control plans for children ≤24 months were allowed. Local failure (LF) on ARST0531 was compared to LF on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n=55), the 5-year cumulative incidence of LF was 13.4%; for group III alveolar RMS (n=141), 20.2%; and for group III embryonal RMS (n=228), 27.9% (p=0.03). Among patients with group III disease, LF did not differ by histology, site, nodal status, RT modality, or treatment arm. LF was worse for tumor size >5cm (32.3% vs 16.7%, p=0.001). Among patients with group III embryonal RMS, LF was higher on ARST0531 compared to D9803 (27.9% vs 19.4%, p=0.03). After excluding patients ≤24 months or patients who did not receive radiation, LF remained significantly increased on ARST0531 (p=0.02). After adjusting for clinical prognostic factors, event-free and overall survival were worse on ARST0531 (p=0.004 and p=0.05). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 compared to D9803. The reason for this is unclear but could be due to the reduced cyclophosphamide dose on ARST0531.

International Journal of Radiation Oncology*Biology*Physics