Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration

Wilde, David; Castro, Patricia; Bera, Kaustav; Lai, Syeling; Madabhushi, Anant; Corredor, Germán; Koyuncu, Can; Lewis, James S.; Lu, Cheng; Frederick, Mitchell J.; Frederick, Allan M; Haugen, A.; Zevallos, José P.; Shi, Justin; Huang, Andrew T.; Hernandez, David J.; Skinner, Heath D.; Kemnade, Jan O.; Yu, Wendong; Sikora, Andrew G.; Sandulache, Vlad C.

doi:10.1038/s41379-022-01024-8

Cited by 17 publications

(23 citation statements)

References 47 publications

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“…On one hand, Veterans with OPSCC are older, with a higher comorbidity burden compared to the general population and thus a reduced ability to tolerate toxic chemotherapy regimens. On the other hand, Veterans consistently demonstrate inferior oncologic outcomes to the general population, which we have shown is driven by more aggressive disease biology which extends to the otherwise favorable HPV‐associated OPSCC subset of disease 10–13 . Optimal deployment of cisplatin in this population remains far from clear and granular institutional datasets are lacking.…”

Section: Introductionmentioning

confidence: 79%

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes

Soliman

Wilde

Kemnade

et al. 2023

Laryngoscope Investig Oto

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ObjectiveCisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity.MethodsWe retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo‐radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab.ResultsPatients with HPV‐associated tumors and nonsmokers demonstrated improved overall and disease‐free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen.ConclusionsBoth HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens.Level of Evidence4.

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Section: Introductionmentioning

confidence: 79%

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes

Soliman

Wilde

Kemnade

et al. 2023

Laryngoscope Investig Oto

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“…Some other researchers analyzed pathological image features like microsatellite instability 28 and multinucleation 29 to incorporate histopathology data. Some researchers also quantified and clustered expression of Proto‐oncogenes (such as MMP11 and CTHRC1) and tumor suppressor genes (such as SPRR3, CDKN2A, and TP53) to relate genetic heterogeneity and Immune‐related adverse events, and performed survival analysis 14,30 . Our study is the first to comprehensively integrate image features of protein marker and multi‐clinical factors for survival analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers also quantified and clustered expression of Proto-oncogenes (such as MMP11 and CTHRC1) and tumor suppressor genes (such as SPRR3, CDKN2A, and TP53) to relate genetic heterogeneity and Immunerelated adverse events, and performed survival analysis. 14,30 Our study is the first to comprehensively integrate image features of protein marker and multi-clinical factors for survival analysis. By integrating multidimensional data sources with advanced machine learning techniques, our pioneering methodology enables more accurate and reliable patient-specific survival estimates.…”

Section: Cep Score As a Relatively Independent Prognostic Factormentioning

confidence: 99%

Prognostic significance of cyclin D1 expression pattern in HPV‐negative oral and oropharyngeal carcinoma: A deep‐learning approach

Yang,

Zhu,

Sun

et al. 2023

J Oral Pathology Medicine

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BackgroundWe aimed to establish image recognition and survival prediction models using a novel scoring system of cyclin D1 expression pattern in patients with human papillomavirus‐negative oral or oropharyngeal squamous cell carcinoma.MethodsThe clinicopathological data of 610 patients with human papillomavirus‐negative oral/oropharyngeal squamous cell carcinoma were analyzed retrospectively. Cox univariate and multivariate risk regression analyses were performed to compare cyclin D1 expression pattern scoring with the traditional scoring method—cyclin D1 expression level scoring—in relation to patients' overall and progression‐free survival. An image recognition model employing the cyclin D1 expression pattern scoring system was established by YOLOv5 algorithms. From this model, two independent survival prediction models were established using the DeepHit and DeepSurv algorithms.ResultsCyclin D1 had three expression patterns in oral and oropharyngeal squamous cell carcinoma cancer nests. Superior to cyclin D1 expression level scoring, cyclin D1 expression pattern scoring was significantly correlated with the prognosis of patients with oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). Moreover, it was an independent prognostic risk factor in both oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). The cyclin D1 expression pattern‐derived image recognition model showed an average test set accuracy of 78.48% ± 4.31%. In the overall survival prediction models, the average concordance indices of the test sets established by DeepSurv and DeepHit were 0.71 ± 0.02 and 0.70 ± 0.01, respectively.ConclusionCombined with the image recognition model of the cyclin D1 expression pattern, the survival prediction model had a relatively good prediction effect on the overall survival prognosis of patients with human papillomavirus‐negative oral or oropharyngeal squamous cell carcinoma.

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“…3,4 However, there remains a significant subset of patients, particularly Veterans, with intermediate (p16+ smokers) and high-risk (p16−) OPSCC that requires multimodality treatment which often involves complex resection and MVFTT. [5][6][7][8][9][10][11][12][13][14] Veterans present with a disproportionate burden of head and neck cancer in several respects. Across all disease sites, they present with more advanced T-and N-classification.…”

mentioning

confidence: 99%

“…The epidemic rise of HPV‐mediated oropharyngeal SCC (OPSCC) has given way to the use of primary radiation, minimally invasive/transoral surgery, and occasionally de‐escalation protocols for low‐risk disease in nonsmokers 3,4 . However, there remains a significant subset of patients, particularly Veterans, with intermediate (p16+ smokers) and high‐risk (p16−) OPSCC that requires multimodality treatment which often involves complex resection and MVFTT 5–14 …”

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confidence: 99%

Operationalizing a Free Flap Program for Head and Neck Reconstruction at a Veterans Affairs Hospital

Hernandez,

Xu,

Lim

et al. 2023

OTO Open

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ObjectivesWe aimed to operationalize a head and neck microvascular free tissue transfer (MVFTT) program at a Veterans Affairs (VA) hospital with the emphasis on initiating radiotherapy within 6 weeks of surgery for cancer patients and minimizing readmissions.Study DesignCase series.SettingTertiary care VA hospital.MethodsA retrospective analysis was performed on consecutive head and neck MVFTT patients from May 1, 2017 and April 30, 2022. Demographics, patient and disease characteristics, per‐operative data and postoperative outcomes were recorded from the electronic medical record. We sought to compare our rate of 30‐day readmissions with those published in the literature.ResultsOne hundred and forty‐one procedures were performed in the queried timeframe. Eighty‐four percent (119) were performed after oncologic resections and 16% (22) were for nononcologic procedures. The rate of total flap loss was <1% and the rate of partial flap loss was 3.5%. For mucosal defects, the fistula rate was 2.3%. The rate of return to the OR for any reason within 30 days was 7.8%. The 30‐day readmission rate was 6.4% while the rates reported in the literature range from 13% to 20%. One hundred and four patients required postoperative radiotherapy (PORT) and 76% started PORT within 42 days of surgery.ConclusionOperationalizing a head and neck MVFTT program with a VA hospital is safe and allows for the successful delivery of multimodality treatment to cancer patients. These resources can be expanded for the care of head and neck cancer treatment sequelae, such as osteoradionecrosis, and other nononcologic patient needs.

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Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration

Cited by 17 publications

References 47 publications

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes

Prognostic significance of cyclin D1 expression pattern in HPV‐negative oral and oropharyngeal carcinoma: A deep‐learning approach

Operationalizing a Free Flap Program for Head and Neck Reconstruction at a Veterans Affairs Hospital

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