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A Phase II Trial Evaluating Rapid Mid-Treatment Nodal Shrinkage to Select for Adaptive Deescalation in p16+Oropharyngeal Cancer Patients Undergoing Definitive Chemoradiation [Meeting Abstract]

Kim, J. K.; Tam, M.; Karp, J. M.; Oh, C.; Kim, G.; Solomon, E.; Concert, C. M.; Vaezi, A. E.; Li, Z.; Tran, T.; Zan, E.; Corby, P.; Feron-Rigodon, M.; Fitz, C. Del Vecchio; Goldberg, J. D.; Hochman, T.; Givi, B.; Jacobson, A.; Persky, M.; Hu, K. S.
ISI:001079706803134
ISSN: 0360-3016
CID: 5591182

Pulmonary Toxic Effects After Myeloablative Conditioning With Total Body Irradiation Delivered via Volumetric Modulated Arc Therapy With Fludarabine

Modrek, Aram S; Karp, Jerome M; Byun, David; Gerber, Naamit K; Abdul-Hay, Maher; Al-Homsi, Ahmad Samer; Galavis, Paulina; Teruel, Jose; Yuan, Ye
We present the case of a 56-year-old female with a diagnosis of acute T-cell lymphoblastic leukemia who received myeloablative conditioning for bone marrow transplant with total body irradiation (TBI) using volumetric modulated arc therapy (VMAT) to the upper body and anterior-posterior/posterior-anterior (AP/PA) open fields to the lower body followed by hematopoietic stem cell transplant. Her clinical course was complicated by high-grade pulmonary toxic effects 55 days after treatment that resulted in death. We discuss the case, planning considerations by radiation oncologists and radiation physicists, and the multidisciplinary medical management of this patient.
PMID: 35598860
ISSN: 1879-8519
CID: 5275182

Disparities in the uptake of telemedicine and implications for clinical trial enrollment in breast cancer patients

Hardy-Abeloos, Camille; Karp, Jerome; Xiao, Julie; Oh, Cheongeun; Barbee, David; Maisonet, Olivier; Gerber, Naamit
PURPOSE/OBJECTIVES/OBJECTIVE:Since the COVID-19 pandemic, telemedicine has emerged as an alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult via telemedicine and correlation with clinical trial enrollment. MATERIALS/METHODS/METHODS:We evaluated breast cancer patients seen during the open enrollment of a prospective randomized trial from 06/01/2020 to 05/13/2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual vs in-person initial consultation. All statistical tests were two-sided and the null hypothesis was rejected for p<0.05. RESULTS:We identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt and radiation at our institution were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial and of those eligible, 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial and of those eligible, 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits. CONCLUSION/CONCLUSIONS:Older patients, unemployed patients, those receiving chemotherapy and those who subsequently received radiation at our institution were less likely to use telemedicine for their initial consult. Despite these disparities in telemedicine usage, there was no difference in clinical trial enrollment. Telemedicine may be an effective platform for clinical trial enrollment though further strategies to improve its access are essential.
PMCID:9584760
PMID: 36273521
ISSN: 1879-355x
CID: 5359182

DNA methylation-based epigenetic signatures predict somatic genomic alterations in gliomas

Yang, Jie; Wang, Qianghu; Zhang, Ze-Yan; Long, Lihong; Ezhilarasan, Ravesanker; Karp, Jerome M; Tsirigos, Aristotelis; Snuderl, Matija; Wiestler, Benedikt; Wick, Wolfgang; Miao, Yinsen; Huse, Jason T; Sulman, Erik P
Molecular classification has improved diagnosis and treatment for patients with malignant gliomas. However, classification has relied on individual assays that are both costly and slow, leading to frequent delays in treatment. Here, we propose the use of DNA methylation, as an emerging clinical diagnostic platform, to classify gliomas based on major genomic alterations and provide insight into subtype characteristics. We show that using machine learning models, DNA methylation signatures can accurately predict somatic alterations and show improvement over existing classifiers. The established Unified Diagnostic Pipeline (UniD) we develop is rapid and cost-effective for genomic alterations and gene expression subtypes diagnostic at early clinical phase and improves over individual assays currently in clinical use. The significant relationship between genetic alteration and epigenetic signature indicates broad applicability of our approach to other malignancies.
PMCID:9338285
PMID: 35906213
ISSN: 2041-1723
CID: 5277052

ADAPTIVE RESPONSES TO GENOME-WIDE DNA DAMAGE RESULT IN TOPOLOGIC GENOME REORGANIZATION IN GLIOBLASTOMA [Meeting Abstract]

Modrek, Aram; Do, Catherine; Zhang, Zeyan; Deng, Yingwen; Karp, Jerome; Ezhilarasan, Ravesanker; Valor, Belen; Cova, Giulia; Jafari, Matiar; Snuderl, Matija; Tsirigos, Aristotelis; Skok, Jane; Sulman, Erik
ISI:000888571000458
ISSN: 1522-8517
CID: 5526662

DNA damage drives DNA methylation and 3D chromatin organization alterations in glioblastoma [Meeting Abstract]

Modrek, Aram S.; Do, Catherine; Zhang, Zeyan; Deng, Yingwen; Karp, Jerome; Ezhilarasan, Ravesanker; Cova, Giulia; Snuderl, Matija; Tsirigos, Aristotelis; Skok, Jane; Sulman, Erik P.
ISI:000892509507561
ISSN: 0008-5472
CID: 5526672

Including Surgical Resection in the Multimodal Management of Very Locally Advanced Sinonasal Cancer

Karp, Jerome M; Hu, Kenneth S; Persky, Michael; Persky, Mark; Jacobson, Adam; Tran, Theresa; Li, Zujun; Givi, Babak; Tam, Moses M
OBJECTIVE:Sinonasal cancer often presents as locoregionally advanced disease. National guidelines recommend management of stage T4b tumors with systemic therapy and radiotherapy, but recent studies suggest that including surgical resection in the multimodal treatment of these tumors may improve local control and survival. We queried the National Cancer Database to examine patterns of care and outcomes in T4b sinonasal squamous cell carcinoma (SCC). STUDY DESIGN/METHODS:Prospectively gathered data. SETTING/METHODS:National Cancer Database. METHODS:Patients with T4b N0-3 M0 sinonasal squamous cell carcinoma diagnosed in 2004 to 2016 were stratified between those who received chemoradiotherapy and those who underwent surgical resection with neoadjuvant or adjuvant treatment. The overall survival of each cohort was assessed via Kaplan-Meier analysis and Cox proportional hazard models, with repeat analysis after reweighting of data via inverse probability of treatment weighting. RESULTS:= .004]). CONCLUSION/CONCLUSIONS:Surgical treatment with neoadjuvant or adjuvant treatment for stage T4b sinonasal SCC was associated with promising survival outcomes, suggesting a role for incorporating surgery in treatment of select T4b SCC, particularly when removal of all macroscopic disease is feasible.
PMID: 34962843
ISSN: 1097-6817
CID: 5108122

Radiotherapy in Metastatic Oropharyngeal Cancer

Nguy, Susanna; Oh, Cheongeun; Karp, Jerome M; Wu, Shengyang Peter; Li, Zujun; Persky, Michael J; Hu, Kenneth S; Givi, Babak; Tam, Moses M
OBJECTIVES/OBJECTIVE:The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy. METHODS:We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors. RESULTS:Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001). CONCLUSION/CONCLUSIONS:The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2020.
PMID: 33141455
ISSN: 1531-4995
CID: 4662912

Early Stage Pregnancy During Radiation Therapy to the Breast

Karp, Jerome M; Teruel, Jose; Gerber, Naamit K
We describe a model case of unplanned pregnancy during radiation therapy to the chest wall and peripheral lymphatics for breast cancer. We use the Morbidity and Mortality Conference format to demonstrate how radiation oncology departments should evaluate and manage this situation.
PMID: 33676632
ISSN: 1879-8519
CID: 4835872

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma

Shah, Bhartesh A; Oh, Cheongeun; Wu, S Peter; Karp, Jerome M; Grossbard, Michael; Gerber, Naamit K
INTRODUCTION/BACKGROUND:Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. PATIENTS AND METHODS/METHODS:The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. RESULTS:Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). CONCLUSION/CONCLUSIONS:Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.
PMID: 32800712
ISSN: 2152-2669
CID: 4572982