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Article ; Online: Radiotherapy, lymphopenia and improving the outcome for glioblastoma: a narrative review.

Kut, Carmen / Kleinberg, Lawrence

2023 Volume 12, Issue 1, Page(s) 4

Abstract: Background and objective: Standard treatment for glioblastoma includes maximal safe resection followed by adjuvant radiation and concurrent temozolomide for 6 weeks, followed by 6 months of maintenance temozolomide; additionally, concurrent high doses ... ...

Abstract	Background and objective: Standard treatment for glioblastoma includes maximal safe resection followed by adjuvant radiation and concurrent temozolomide for 6 weeks, followed by 6 months of maintenance temozolomide; additionally, concurrent high doses of corticosteroids are required for many patients to reduce intracranial pressure and reduce inflammatory side effects. This combination of cytotoxic therapies (including radiotherapy, temozolomide, and corticosteroids) often results in severe treatment-related lymphopenia that can persist beyond the duration of therapy. Methods: Papers on treatment-related lymphopenia were retrieved to analyze the role of lymphocytes in tumor control, the role of radiotherapy in inducing lymphopenia, understand other contributing factors to lymphopenia and investigate strategies (including altered radiation approaches) that may reduce the impact of lymphopenia for patients with glioblastoma in the future. Key content and findings: Radiation, in particular, plays an important role in lymphopenia. Lymphocytes are considered the most radiosensitive cells in the human body, and ionizing radiation often results in apoptotic response and rapid death of lymphocytes within hours of exposure. As a result, radiotherapy can lead to systemic immunosuppression including lymphopenia which is permissive of tumor growth and is linked to impaired local control and reduced survival. For this reason, interactions between radiotherapy treatment and the immune response to tumor is the subject of active study. This study also explores promising lymphocyte-medicated immune therapies which have developed clinical use for many non-glioblastoma cancer types, with promising preclinical results in glioblastoma treatment. Conclusions: Limiting treatment-related lymphopenia is especially important in improving treatment outcomes for glioblastoma. Research on strategies to reduce the impact of lymphopenia may promote improved treatment outcomes for glioblastoma patients.
MeSH term(s)	Humans ; Temozolomide/therapeutic use ; Brain Neoplasms/radiotherapy ; Brain Neoplasms/drug therapy ; Glioblastoma/radiotherapy ; Glioblastoma/drug therapy ; Lymphopenia/etiology ; Treatment Outcome ; Radiotherapy
Chemical Substances	Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2023-02-26
Publishing country	China
Document type	Review ; Journal Article
ZDB-ID	2828547-5
ISSN	2304-3873 ; 2304-3873
ISSN (online)	2304-3873
ISSN	2304-3873
DOI	10.21037/cco-22-94
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Article ; Online: A 55-Year-Old Man With Cough and Hematochezia.

Kut, Carmen / Sabath, Bruce F

Chest

2020 Volume 157, Issue 4, Page(s) e121–e125

Abstract: Case presentation: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had ... ...

Abstract	Case presentation: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.
MeSH term(s)	Airway Obstruction/diagnostic imaging ; Airway Obstruction/etiology ; Airway Obstruction/pathology ; Airway Obstruction/therapy ; Antirheumatic Agents/administration & dosage ; Bronchoscopy/methods ; Colitis, Ulcerative/complications ; Colitis, Ulcerative/physiopathology ; Colitis, Ulcerative/therapy ; Cough/diagnosis ; Cough/etiology ; Cryosurgery/methods ; Diagnosis, Differential ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/etiology ; Glucocorticoids/administration & dosage ; Humans ; Infliximab/administration & dosage ; Male ; Middle Aged ; Necrosis/complications ; Necrosis/pathology ; Necrosis/therapy ; Respiration, Artificial/methods ; Respiratory Distress Syndrome/diagnosis ; Respiratory Distress Syndrome/etiology ; Respiratory Distress Syndrome/physiopathology ; Respiratory Distress Syndrome/therapy ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; Ulcer/etiology ; Ulcer/pathology
Chemical Substances	Antirheumatic Agents ; Glucocorticoids ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2020-04-02
Publishing country	United States
Document type	Case Reports
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2019.10.027
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Ui III Zs.45: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 349: Show issues

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Article ; Online: Factors Impacting Provider Treatment Decision-Making in Early Glottic Cancer.

Shneyderman, Matthew / Shen, Sarek / Tanavde, Ved / Kut, Carmen / Kiess, Ana P / Naunheim, Matthew R / Akst, Lee M

The Laryngoscope

2024

Abstract: Objectives: Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case-dependent provider treatment preferences and identify factors which impact decision-making in ...

Abstract	Objectives: Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case-dependent provider treatment preferences and identify factors which impact decision-making in EGC. Methods: This cross-sectional survey of laryngologists, head-and-neck surgeons, and radiation oncologists presented five diagrammatic cases of progressively advanced EGC (T1/2, N0). Respondents indicated preference for TLMS or XRT and ranked factors which influenced their recommendation for each case. Analysis utilized descriptive statistics, Fischer's exact tests, and Kruskal-Wallis tests for nonparametric data. Results: A total of 141 complete responses (69.5% laryngologists) were received. Most respondents practiced in academic settings (93.5%) and within multidisciplinary teams (94.0%). Anterior commissure involvement was the most important a priori tumor factor for case-independent treatment recommendation (Likert Scale: 4.22/5), followed by Laterality (Likert Scale: 4.02/5). Across all specialties, TLMS was recommended for unilateral T1a lesions. Laryngologists continued recommending TLMS in T2 lesions (41.0%) more than head-and-neck surgeons (5.0%) and radiation oncologists (0.0%). Across all cases, survival and voice outcomes were the most important clinical factors impacting treatment decisions. Radiation oncologists weighed voice more heavily than laryngologists in more complex presentations of EGC (rank: 1.6 vs. 2.7, Kruskall-Wallis: p < 0.05). Conclusions: In more complex clinical presentations of EGC, preference for TLMS compared to XRT differed across specialists, despite similar rankings of factors driving these treatment recommendations. This may be driven by differing experiences and viewpoints on case-dependent voice outcomes following TLMS versus XRT, suggesting a need for increased understanding of how tumor location and depth impact voice outcomes. Level of evidence: V Laryngoscope, 2024.
Language	English
Publishing date	2024-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.31494
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Ul II Zs.82: Show issues

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Article ; Online: 3D-printed Magnetic Resonance (MR)-based gynecological phantom for image-guided brachytherapy training.

Kut, Carmen / Kao, Tracy / Morcos, Marc / Kim, Younsu / Boctor, Emad / Viswanathan, Akila N

Brachytherapy

2022 Volume 21, Issue 6, Page(s) 799–805

Abstract: Purpose/objectives: There is a clinical need to develop anatomic phantoms for simulation-based learning in gynecological brachytherapy. Here, we provide a step-by-step approach to build a life-sized gynecological training phantom based on magnetic ... ...

Abstract	Purpose/objectives: There is a clinical need to develop anatomic phantoms for simulation-based learning in gynecological brachytherapy. Here, we provide a step-by-step approach to build a life-sized gynecological training phantom based on magnetic resonance imaging (MRI) of an individual patient. Our hypothesis is that this phantom can generate convincing ultrasound (US) images that are similar to patient scans. Methods: Organs-at-risk were manually segmented using patient scans (MRI). The gynecological phantom was constructed using positive molds from 3D printing and polyvinyl chloride (PVC) plastisol. Tissue texture/acoustic properties were simulated using different plastic softener/hardener ratios and microbead densities. Nine readers (residents) were asked to evaluate 10 cases (1 ultrasound image per case) and categorize each as a "patient" or "phantom" image. To evaluate whether the phantom and patient images were equivalent, we used a multireader, multicase equivalence study design with two composite null hypotheses with proportion (p Results: Readers correctly classified "patient" and "phantom" scans at p Conclusions: We have outlined a manufacturing process to create a life-sized, gynecological phantom that is compatible with multi-modality imaging and can be used to simulate clinical scenarios in image-guided brachytherapy procedures.
MeSH term(s)	Humans ; Brachytherapy/methods ; Phantoms, Imaging ; Magnetic Resonance Imaging/methods ; Tomography, X-Ray Computed/methods ; Magnetic Resonance Spectroscopy
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2098608-7
ISSN	1873-1449 ; 1538-4721
ISSN (online)	1873-1449
ISSN	1538-4721
DOI	10.1016/j.brachy.2022.07.005
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Article ; Online: Clinical Uncertainties of Circulating Tumor DNA in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma in the Absence of National Comprehensive Cancer Network Guidelines.

Xie, Deborah X / Kut, Carmen / Quon, Harry / Seiwert, Tanguy Y / D'Souza, Gypsyamber / Fakhry, Carole

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2022 Volume 41, Issue 14, Page(s) 2483–2487

MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck ; Human Papillomavirus Viruses ; Circulating Tumor DNA/genetics ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Papillomaviridae/genetics ; Head and Neck Neoplasms ; Oropharyngeal Neoplasms/therapy ; Oropharyngeal Neoplasms/pathology ; Papillomavirus Infections/complications
Chemical Substances	Circulating Tumor DNA
Language	English
Publishing date	2022-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.00264
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Developing the POTOMAC Model: A Novel Prediction Model to Study the Impact of Lymphopenia Kinetics on Survival Outcomes in Head and Neck Cancer Via an Ensemble Tree-Based Machine Learning Approach.

Kut, Carmen / Midthune, Doug / Lee, Emerson / Fair, Peyton / Cheunkarndee, Tia / McNutt, Todd / DeWeese, Theodore / Fakhry, Carole / Kipnis, Victor / Quon, Harry

JCO clinical cancer informatics

2023 Volume 7, Page(s) e2300058

Abstract: Purpose: Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline ... ...

Abstract	Purpose: Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline versus treatment-related lymphopenia, a robust analysis is necessary to investigate the relative importance of various lymphopenia metrics (LMs) in predicting survival outcomes. Methods: In this prospective cohort study, 363 patients were eligible for analysis (patients with newly diagnosed, nonmetastatic HNSCC treated with neck radiation with or without chemotherapy in 2015-2019). Data were acquired on 28 covariates: seven baseline, five disease, seven treatment, and nine LMs, including static and time-varying features for absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio, and immature granulocytes (IGs). IGs were included, given their hypothesized role in inhibiting lymphocyte function. Overall, there were 4.0% missing data. Median follow-up was 2.9 years. We developed a model (POTOMAC) to predict survival outcomes using a random survival forest (RSF) procedure. RSF uses an ensemble approach to reduce the risk of overfitting and provides internal validation of the model using data that are not used in model development. The ability to predict survival risk was assessed using the AUC for the predicted risk score. Results: POTOMAC predicted 2-year survival with AUCs at 0.78 for overall survival (primary end point) and 0.73 for progression-free survival (secondary end point). Top modifiable risk factors included radiation dose and max ALC decrease. Top baseline risk factors included age, Charlson Comorbidity Index, Karnofsky Performance Score, and baseline IGs. Top-ranking LMs had superior prognostic performance when compared with human papillomavirus status, chemotherapy type, and dose (up to 2, 8, and 65 times higher in variable importance score). Conclusion: POTOMAC provides important insights into potential approaches to reduce mortality in patients with HNSCC treated by chemoradiation but needs to be validated in future studies.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/therapy ; Prospective Studies ; Lymphopenia/etiology ; Lymphopenia/diagnosis ; Lymphocyte Count ; Head and Neck Neoplasms/diagnosis ; Head and Neck Neoplasms/therapy ; Head and Neck Neoplasms/complications
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article
ISSN	2473-4276
ISSN (online)	2473-4276
DOI	10.1200/CCI.23.00058
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Article ; Online: Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection.

Yuan, Wu / Kut, Carmen / Liang, Wenxuan / Li, Xingde

Scientific reports

2017 Volume 7, Page(s) 44909

Abstract: Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of ... ...

Abstract	Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.
MeSH term(s)	Algorithms ; Brain Neoplasms/diagnostic imaging ; Disease Management ; Humans ; Phantoms, Imaging ; Reproducibility of Results ; Signal Processing, Computer-Assisted ; Tomography, Optical Coherence/methods ; Tomography, Optical Coherence/standards
Language	English
Publishing date	2017-03-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep44909
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Article ; Online: New considerations in radiation treatment planning for brain tumors: neural progenitor cell-containing niches.

Kut, Carmen / Janson Redmond, Kristin

Seminars in radiation oncology

2014 Volume 24, Issue 4, Page(s) 265–272

Abstract: The purpose of this critical review is to explore the controversy regarding the relationship between radiation dose to the neural progenitor cell (NPC) niches and patient outcomes, in terms of both toxicity and tumor control. NPCs in the subventricular ... ...

Abstract	The purpose of this critical review is to explore the controversy regarding the relationship between radiation dose to the neural progenitor cell (NPC) niches and patient outcomes, in terms of both toxicity and tumor control. NPCs in the subventricular zone (SVZ) and hippocampus are paradoxically associated with long-term neurocognitive sequelae of brain irradiation, as well as resistance to therapy and tumor recurrence. The reconciliation of these somewhat opposing functions is challenging. Current literature suggests that radiation and other treatments against the NPC in the hippocampus and the SVZ may influence patient outcome. As a result, both the SVZ and the hippocampus could have important implications on radiation treatment planning strategies, and future laboratory and clinical evaluations will be critical in designing studies to optimize treatment outcome, effectiveness, and safety.
MeSH term(s)	Brain/pathology ; Brain Neoplasms/radiotherapy ; Cranial Irradiation/methods ; Humans ; Neural Stem Cells/radiation effects ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Stem Cell Niche/radiation effects
Language	English
Publishing date	2014-07-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2014.06.007
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Article ; Online: Intraoperative imaging techniques for glioma surgery.

Garzon-Muvdi, Tomas / Kut, Carmen / Li, Xingde / Chaichana, Kaisorn L

Future oncology (London, England)

2017 Volume 13, Issue 19, Page(s) 1731–1745

Abstract: Gliomas are CNS neoplasms that infiltrate the surrounding brain parenchyma, complicating their treatment. Tools that increase extent of resection while preventing neurological deficit are essential to improve prognosis of patients diagnosed with gliomas. ...

Abstract	Gliomas are CNS neoplasms that infiltrate the surrounding brain parenchyma, complicating their treatment. Tools that increase extent of resection while preventing neurological deficit are essential to improve prognosis of patients diagnosed with gliomas. Tools such as intraoperative MRI, ultrasound and fluorescence-guided microsurgery have been used in the surgical resection of CNS gliomas with the goal of maximizing extent of resection to improve patient outcomes. In addition, emerging experimental techniques, for example, optical coherence tomography and Raman spectroscopy are promising techniques which could 1 day add to the increasing armamentarium used in the surgical resection of CNS gliomas. Here, we present the potential advantages and limitations of these imaging techniques for the purposes of identifying gliomas in the operating room.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/surgery ; Diagnostic Imaging/methods ; Glioma/diagnostic imaging ; Glioma/surgery ; Humans ; Intraoperative Care ; Magnetic Resonance Imaging ; Spectrum Analysis, Raman ; Surgery, Computer-Assisted ; Tomography, Optical Coherence ; Ultrasonography
Language	English
Publishing date	2017-08-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2184533-5
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2017-0092
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Article: Improving Quality Metrics in Radiation Oncology: Implementation of Pretreatment Peer Review for Stereotactic Body Radiation Therapy in Patients with Thoracic Cancer.

Kut, Carmen / Chang, Leslie / Hales, Russell K / Voong, K Ranh / Greco, Stephen / Halthore, Aditya / Alcorn, Sara R / Song, Daniel / Briner, Valerie / McNutt, Todd R / Viswanathan, Akila N / Wright, Jean L

Advances in radiation oncology

2022 Volume 8, Issue 2, Page(s) 101004

Abstract: Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority ... ...

Abstract	Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority for contour/plan review before the start of treatment, considering both the rapid-dose falloff and short treatment course. Yet, peer-review goals for SBRT must also balance physician time demands and the desire to avoid routine treatment delays that would occur in the setting of a 100% pretreatment (pre-Tx) review compliance requirement or prolonging the standard treatment planning timeline. Herein, we report on our pilot experience of a pre-Tx peer review of thoracic SBRT cases. Methods and materials: From March 2020 to August 2021, patients undergoing thoracic SBRT were identified for pre-Tx review, and placed on a quality checklist. We implemented twice-weekly meetings for detailed pre-Tx review of organ-at-risk/target contours and dose constraints in the treatment planning system for SBRT cases. Our quality metric goal was to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. We used a statistical process control chart with sigma limits (ie, standard deviations [SDs]) to access compliance rates with pre-Tx review implementation. Results: We identified 252 patients treated with SBRT to 294 lung nodules. When comparing pre-Tx review completion from initial rollout to full implementation, our rates improved from 19% to 79% (ie, from 1 sigma limit [SDs]) below to >2 sigma limits (SDs) above. Additionally, early completion of any form of contour/plan review (defined as any pre-Tx or standard review completed before exceeding 25% of the dose delivered) increased from 67% to 85% (March 2020-November 2020) to 76% to 94% (December 2020-August 2021). Conclusions: We successfully implemented a sustainable workflow for detailed pre-Tx contour/plan review for thoracic SBRT cases in the context of twice-weekly disease site-specific peer-review meetings. We reached our quality improvement objective to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. This process was feasible to conduct in an integrated network of sites across our system.
Language	English
Publishing date	2022-10-25
Publishing country	United States
Document type	Journal Article
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2022.101004
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