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  1. Article ; Online: Exploring the function of myeloid cells in promoting metastasis in head and neck cancer.

    Okwuone, Dakota Dike Dimegwu / Morgan, Deri / Gan, Gregory N

    Exploration of targeted anti-tumor therapy

    2024  Volume 5, Issue 1, Page(s) 108–119

    Abstract: Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient survival rates. Expanding the understanding of the ... ...

    Abstract Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient survival rates. Expanding the understanding of the mechanisms of the metastatic cascade is critical for creating more effective therapeutics that improve outcomes for HNC patients. A true grasp of cancer metastasis requires the consideration of all cell types that contribute to the inflammatory HNC microenvironment as drivers of this process. More emphasis now is being placed on exploring the roles of the different immune cells in cancer control, tumorigenesis and metastasis. Myeloid cells are the most numerous immune cell types in the body, and they are actively recruited and reprogrammed by tumor cells to behave in a variety of ways. These cells are remarkably diverse in phenotype and function, and the part they play in tumor spread greatly differs based on the cell type. This review will focus on summarizing the roles of macrophages, neutrophils, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs) in driving HNC metastasis by examining the current knowledge base and offering potential new routes through which to target and treat this deadly process.
    Language English
    Publishing date 2024-02-19
    Publishing country United States
    Document type Journal Article
    ISSN 2692-3114
    ISSN (online) 2692-3114
    DOI 10.37349/etat.2024.00208
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  2. Article ; Online: Development and characterization of the first proton minibeam system for single-gantry proton facility.

    Lin, Yuting / Li, Wangyao / Johnson, Daniel / Prezado, Yolanda / Gan, Gregory N / Gao, Hao

    Medical physics

    2024  

    Abstract: Background: Minibeam represents a preclinical spatially fractionated radiotherapy modality with great translational potential. The advantage lies in its high therapeutic index (compared to GRID and LATTICE) and ability to treat at greater depth ( ... ...

    Abstract Background: Minibeam represents a preclinical spatially fractionated radiotherapy modality with great translational potential. The advantage lies in its high therapeutic index (compared to GRID and LATTICE) and ability to treat at greater depth (compared to microbeam). Proton minibeam radiotherapy (pMBRT) is a synergy of proton and minibeam. While the single-gantry proton facility has gained popularity due to its affordability and compact design, it often has limited beam time available for research purposes. Conversely, given the current requirement of pMBRT on specific minibeam hardware collimators, necessitates a reproducible and fast setup to minimize pMBRT treatment time and streamline the switching time between pMBRT and conventional treatment for clinically translation.
    Purpose: The contribution of this work is the development and characterization of the first pMBRT system tailored for single-gantry proton facility. The system allows for efficient and reproducible plug-and-play setup, achievable within minutes.
    Methods: The single room pMBRT system is constructed based on IBA ProteusONE proton machine. The end of nozzle is attached with beam modifying accessories though an accessory drawer. A small snout is attached to the accessory drawer and used to hold apertures and range shifters. The minibeam aperture consists of two components: a fitting ring and an aperture body. Three minibeam apertures were manufactured. The first-generation apertures underwent qualitatively analysis with film, and the second generation aperture underwent more comprehensive quantitative measurement. The reproducibility of the setup is accessed, and the film measurements are performed to characterize the pMBRT system in cross validation with Monte Carlo (MC) simulations.
    Results: We presented initial results of large field pMBRT aperture and the film measurements indicates the effect of source-to-isocenter distance = 930 cm in Y proton scanning direction. Consistent with TOPAS MC simulation, the dose uniformity of pMBRT field <2 cm is demonstrated to be better than 2%, rendering its suitability for pre-clinical studies. Subsequently, we developed the second generation of aperture with five slits and characterized the aperture with film dosimetry studies and compared the results to the benchmark MC. Comprehensive film measurements were also performed to evaluate the effect of divergence, air gap and gantry-angle dependency and repeatability and revealing a consistent performance within 5%. Furthermore, the 2D gamma analysis indicated a passing rate exceeding 99% using 3% dose difference and 0.2 mm distance agreement criteria. We also establish the peak valley dose ratio and the depth dose profile measurements, and the results are within 10% from MC simulation.
    Conclusions: We have developed the first pMBRT system tailored for a single-gantry proton facility, which has demonstrated accuracy in benchmark with MC simulations, and allows for efficient plug-and-play setup, emphasizing efficiency.
    Language English
    Publishing date 2024-04-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 188780-4
    ISSN 2473-4209 ; 0094-2405
    ISSN (online) 2473-4209
    ISSN 0094-2405
    DOI 10.1002/mp.17074
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  3. Article ; Online: Molecular and immune signature of HPV-positive oral cavity squamous cell carcinoma.

    Yilmaz, Emrullah / Ozbun, Michelle A / Gan, Gregory N

    Oral oncology

    2021  Volume 116, Page(s) 105175

    MeSH term(s) Humans ; Mouth Neoplasms ; Papillomaviridae ; Papillomavirus Infections/immunology ; Papillomavirus Infections/metabolism ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/metabolism
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Letter ; Research Support, N.I.H., Extramural
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2020.105175
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    Zs.A 456: Show issues Location:
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  4. Article ; Online: Genomics Reloaded: Rise of the Expression Profiles.

    Gan, Gregory N / Kimple, Randall J

    International journal of radiation oncology, biology, physics

    2018  Volume 101, Issue 1, Page(s) 1–3

    MeSH term(s) Cetuximab ; Epithelial Cells ; Genomics ; Head and Neck Neoplasms ; Heterografts ; Humans
    Chemical Substances Cetuximab (PQX0D8J21J)
    Language English
    Publishing date 2018-04-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2017.10.023
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  5. Article ; Online: IMpower, CASPIAN, and more: exploring the optimal first-line immunotherapy for extensive-stage small cell lung cancer.

    Huang, Chengliang / Gan, Gregory N / Zhang, Jun

    Journal of hematology & oncology

    2020  Volume 13, Issue 1, Page(s) 69

    Abstract: The life expectancy of extensive-stage small cell lung (ES-SCLC) cancer patients has not improved in the last 2-3 decades until two recent trials (CASPIAN and IMpower133) showing the addition of anti-programmed death ligand (PD-L1) therapy to ... ...

    Abstract The life expectancy of extensive-stage small cell lung (ES-SCLC) cancer patients has not improved in the last 2-3 decades until two recent trials (CASPIAN and IMpower133) showing the addition of anti-programmed death ligand (PD-L1) therapy to chemotherapy has survival benefit over chemotherapy alone. However, such benefit is relatively small and was not even observed in some other trials using immunotherapy, raising the question of optimal chemoimmunotherapy combination in the 1st-line setting for ES-SCLC. Here, we discussed several thought-provoking questions with the focus on IMpower133 and CASPIAN trials.
    MeSH term(s) Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; Clinical Trials, Phase III as Topic/statistics & numerical data ; Double-Blind Method ; Drug Synergism ; Etoposide/administration & dosage ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immunotherapy ; Lung Neoplasms/drug therapy ; Multicenter Studies as Topic/statistics & numerical data ; Neoplasm Proteins/antagonists & inhibitors ; Organoplatinum Compounds/administration & dosage ; Progression-Free Survival ; Randomized Controlled Trials as Topic/statistics & numerical data ; Small Cell Lung Carcinoma/drug therapy ; Survival Analysis
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; CD274 protein, human ; Immune Checkpoint Inhibitors ; Neoplasm Proteins ; Organoplatinum Compounds ; durvalumab (28X28X9OKV) ; Etoposide (6PLQ3CP4P3) ; tremelimumab (QEN1X95CIX)
    Language English
    Publishing date 2020-06-05
    Publishing country England
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429631-4
    ISSN 1756-8722 ; 1756-8722
    ISSN (online) 1756-8722
    ISSN 1756-8722
    DOI 10.1186/s13045-020-00898-y
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  6. Article ; Online: Role of molecular signature to differentiate second primary lung cancer from metastasis in a patient with squamous cell carcinoma of oral cavity.

    Yilmaz, Emrullah / Gan, Gregory N / Schroeder, Thomas M / Cowan, Andrew / Joste, Nancy

    Cancer reports (Hoboken, N.J.)

    2021  Volume 4, Issue 4, Page(s) e1363

    Abstract: Background: Lung is the most common site of distant metastasis for patients with head and neck squamous cell carcinoma (HNSCC). However, differentiating second primary lung cancers from metastasis may be difficult for p16 negative HNSCC.: Case: We ... ...

    Abstract Background: Lung is the most common site of distant metastasis for patients with head and neck squamous cell carcinoma (HNSCC). However, differentiating second primary lung cancers from metastasis may be difficult for p16 negative HNSCC.
    Case: We describe a case of oral cavity squamous cell carcinoma (SCC) who was found to have lung nodule and hilar lymphadenopathy (LAD) after surgery and radiation therapy. Hilar node was consistent with SCC however, it was difficult to differentiate second primary lung cancer and metastasis from oral cavity SCC. Next-generation sequencing was done for the primary oral cavity and the hilar node. Both samples had the same type of TP53 mutation and variants of unknown significance suggesting metastatic HNSCC. He was treated with a chemotherapy regimen for metastatic HNSCC.
    Conclusion: Molecular studies can help to differentiate metastasis from second primary lung cancers for p16 negative HNSCC.
    MeSH term(s) Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/genetics ; Diagnosis, Differential ; Humans ; Lung/pathology ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/secondary ; Male ; Mouth/pathology ; Mouth Neoplasms/diagnosis ; Mouth Neoplasms/drug therapy ; Mouth Neoplasms/pathology ; Mutation ; Neoplasms, Second Primary/diagnosis ; Squamous Cell Carcinoma of Head and Neck/diagnosis ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/secondary ; Tumor Suppressor Protein p53/genetics
    Chemical Substances Biomarkers, Tumor ; TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2021-06-23
    Publishing country United States
    Document type Case Reports ; Journal Article
    ISSN 2573-8348
    ISSN (online) 2573-8348
    DOI 10.1002/cnr2.1363
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  7. Article ; Online: Assessing the Risk of Adjuvant Radiotherapy Initiation Delays With Social Support Surveys.

    Renslo, Bryan / Sawaf, Tuleen / Virgen, Celina G / Farrokhian, Nathan / Yu, Katherine M / Somani, Shaan N / Penn, Joseph / Ziegler, Andrea / Gan, Gregory N / Kakarala, Kiran / Shnayder, Yelizaveta / Bur, Andrés M / Sykes, Kevin J

    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

    2023  Volume 169, Issue 4, Page(s) 928–937

    Abstract: Objective: In patients with head and neck squamous cell carcinoma (HNSCC), initiating postoperative radiotherapy (PORT) greater than 42 days after surgery is associated with a higher risk of poor survival outcomes. Social support has been shown to ... ...

    Abstract Objective: In patients with head and neck squamous cell carcinoma (HNSCC), initiating postoperative radiotherapy (PORT) greater than 42 days after surgery is associated with a higher risk of poor survival outcomes. Social support has been shown to modulate behaviors related to care-seeking and treatment adherence. In this study, we sought to determine the relationship between social support metrics and PORT delays.
    Study design: Prospective cohort study.
    Setting: Single tertiary medical center.
    Methods: Patients with HNSCC who underwent primary surgical excision requiring PORT were prospectively enrolled. Patient-perceived social support metrics were assessed using the Medical Outcomes Study Social Support Survey (MOS-SSS) at initial presurgical evaluation. Associations with PORT delays were evaluated via univariable and multivariable logistic regression analysis.
    Results: A total of 111 patients met the inclusion criteria for the study. An additional 28 patients were recommended to receive PORT but did not initiate treatment and were included for secondary analysis. All four subscales of the MOS-SSS (positive social interaction, affectionate support, tangible support, and emotional/informational support) were significantly associated with PORT initiation delays on univariable analysis. On multivariable analysis, the overall MOS-SSS score (odds ratio [OR] 2.08, 1.15-4.35, p = .028) was significantly associated with PORT initiation delays. On secondary analysis, lower tangible support was associated with a lack of PORT initiation (OR 1.63, 1.05-2.54, p = .028).
    Conclusion: Social support metrics were significantly associated with PORT delays, which may help promote tighter scheduling and closer monitoring of high-risk patients.
    MeSH term(s) Humans ; Squamous Cell Carcinoma of Head and Neck ; Radiotherapy, Adjuvant ; Carcinoma, Squamous Cell/pathology ; Prospective Studies ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/surgery ; Social Support ; Retrospective Studies
    Language English
    Publishing date 2023-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 392085-9
    ISSN 1097-6817 ; 0161-6439 ; 0194-5998
    ISSN (online) 1097-6817
    ISSN 0161-6439 ; 0194-5998
    DOI 10.1002/ohn.270
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  8. Article ; Online: Emerging from their burrow: Hedgehog pathway inhibitors for cancer.

    Gan, Gregory N / Jimeno, Antonio

    Expert opinion on investigational drugs

    2016  Volume 25, Issue 10, Page(s) 1153–1166

    Abstract: Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and ... ...

    Abstract Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.
    Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.
    Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Drug Design ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors ; Hedgehog Proteins/metabolism ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/pathology ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects
    Chemical Substances Antineoplastic Agents ; Hedgehog Proteins
    Language English
    Publishing date 2016-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1182884-5
    ISSN 1744-7658 ; 0967-8298 ; 1354-3784
    ISSN (online) 1744-7658
    ISSN 0967-8298 ; 1354-3784
    DOI 10.1080/13543784.2016.1216973
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    Zs.A 3739: Show issues Location:
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  9. Article ; Online: Association of Social-Ecological Factors With Delay in Time to Initiation of Postoperative Radiation Therapy: A Prospective Cohort Study.

    Sawaf, Tuleen / Virgen, Celina G / Renslo, Bryan / Farrokhian, Nathan / Yu, Katherine M / Somani, Shaan N / Bur, Andrés M / Kakarala, Kiran / Shnayder, Yelizaveta / Gan, Gregory N / Graboyes, Evan M / Sykes, Kevin J

    JAMA otolaryngology-- head & neck surgery

    2023  Volume 149, Issue 6, Page(s) 477–484

    Abstract: Importance: Timely initiation of postoperative radiation therapy (PORT) is associated with reduced recurrence rates and improved overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Measurement of the association of social- ... ...

    Abstract Importance: Timely initiation of postoperative radiation therapy (PORT) is associated with reduced recurrence rates and improved overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Measurement of the association of social-ecological variables with PORT delays is lacking.
    Objective: To assess individual and community-level factors associated with PORT delay among patients with HNSCC.
    Design, setting, and participants: This prospective cohort study carried out between September 2018 and June 2022 included adults with untreated HNSCC who were enrolled in a prospective registry at a single academic tertiary medical center. Demographic information and validated self-reported measures of health literacy were obtained at baseline visits. Clinical data were recorded, and participant addresses were used to calculate the area deprivation index (ADI), a measure of community-level social vulnerability. Participants receiving primary surgery and PORT were analyzed. Univariable and multivariable regression analysis was performed to identify risk factors for PORT delays.
    Exposures: Surgical treatment and PORT.
    Main outcomes and measures: The primary outcome was PORT initiation delay (>42 days from surgery). Risk of PORT initiation delay was evaluated using individual-level (demographic, health literacy, and clinical data) and community-level information (ADI and rural-urban continuum codes).
    Results: Of 171 patients, 104 patients (60.8%) had PORT delays. Mean (SD) age of participants was 61.0 (11.2) years, 161 were White (94.2%), and 105 were men (61.4%). Insurance was employer-based or public among 65 (38.5%) and 75 (44.4%) participants, respectively. Mean (SD) ADI (national percentile) was 60.2 (24.4), and 71 (41.8%) resided in rural communities. Tumor sites were most commonly oral cavity (123 [71.9%]), with 108 (63.5%) classified as stage 4 at presentation. On multivariable analysis, a model incorporating individual-level factors with health literacy in addition to community-level factors was most predictive of PORT delay (AOC= 0.78; R2, 0.18).
    Conclusions and relevance: This cohort study provides a more comprehensive assessment of predictors of PORT delays that include health literacy and community-level measures. Predictive models that incorporate multilevel measures outperform models with individual-level factors alone and may guide precise interventions to decrease PORT delay for at-risk patients with HNSCC.
    MeSH term(s) Male ; Adult ; Humans ; Middle Aged ; Female ; Squamous Cell Carcinoma of Head and Neck ; Carcinoma, Squamous Cell/pathology ; Cohort Studies ; Prospective Studies ; Retrospective Studies ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/surgery
    Language English
    Publishing date 2023-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2701825-8
    ISSN 2168-619X ; 2168-6181
    ISSN (online) 2168-619X
    ISSN 2168-6181
    DOI 10.1001/jamaoto.2023.0308
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  10. Article: Sarcopenia and Treatment Toxicity in Older Adults Undergoing Chemoradiation for Head and Neck Cancer: Identifying Factors to Predict Frailty.

    Morse, Ryan T / Ganju, Rohit G / Gan, Gregory N / Cao, Ying / Neupane, Prakash / Kakarala, Kiran / Shnayder, Yelizaveta / Lominska, Christopher E

    Cancers

    2022  Volume 14, Issue 9

    Abstract: This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with ... ...

    Abstract This study was performed to identify treatment related toxicities in older adults undergoing concurrent chemoradiotherapy for head and neck cancer and nutritional and skeletal muscle measures that might identify frailty. Imaging analysis was done with the following skeletal muscle measurements: skeletal muscle index (SMI), skeletal muscle density (SMD), and skeletal muscle gauge (SMG). Patients were dichotomized by age into younger (<70 years old, 221 patients) and older age groups (≥70 years old, 51 patients). Low SMI was more common in older patients (86.7%) compared to younger patients (51.7%, p < 0.01), as were low SMD (57.8% vs. 37.3%, p = 0.012) and low SMG (76.1% vs. 44.2%, p < 0.01), despite having similar BMIs (27.3 kg/m2 versus 27.7 kg/m2, p = 0.71). Older patients were significantly more likely to experience chemotherapy toxicity than younger patients (54.9% versus 32.3%, p < 0.01). On multivariate analysis age (p < 0.01), current smoking status (p < 0.01), and low SMI (p < 0.01) remained as significant predictors for missed chemotherapy cycles or discontinuation. Older patients were more likely to require ≥5-day radiation breaks than younger patients (27.5% versus 8.6%, p < 0.01). On multivariate analysis, age (p < 0.01), low albumin status (p = 0.03), and low SMI (p = 0.04) were identified as predictors of prolonged radiation treatment breaks. Based on the results of our study, sarcopenia may be used as an additional marker for frailty alongside traditional performance status scales.
    Language English
    Publishing date 2022-04-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14092094
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