A predictive survival model for patients with head and neck squamous cell carcinoma treated with immune check point inhibitors

Bonomi, Marcelo; Bhateja, Priyanka; Issa, Majd; Klamer, Brett; Pan, Xueliang; Blakaj, Adriana; Karivedu, Vidhya; Mousa, Luay; Mitchell, Darrion; Gamez, M.E.; Kang, Stephen Y.; Seim, Nolan B.; Old, Matthew; Carrau, Ricardo L.; Rocco, James W.; Blakaj, Dukagjin

doi:10.1016/j.oraloncology.2020.104900

Cited by 5 publications

(5 citation statements)

References 40 publications

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“…Using our original model to predict outcomes for this cohort [15], we found a slightly lower measure of discrimination and similar calibration slope compared to the original internally validated estimates (original internally validated c-index = 0.70 vs. temporal validated c-index = 0.68 and original internally validated calibration slope = 0.68 vs. temporal validated calibration slope = 0.69). In accordance with our previous approach [15], we explored Cox proportional hazard regression models using age, Neu, Lymph, platelet count, Alb, Hb, LDH and p-16 tumor status as predictor variables. Platelet count was removed from the updated model to improve internal validation characteristics and allow for non-linear relationship of Lymph with the log relative hazard (p < 0.001, Fig.…”

Section: Resultsmentioning

confidence: 72%

“…5 Nomogram of overall survival in our cohort cohort the robust reproducibility and statistical strength. Compared to our original cohort [15], we provide evidence for enhanced goodness of fit in our model. Our cohort is unique since we have collected a series of detailed and inexpensive clinical parameters, widely available and easily applicable in every healthcare setting.…”

Section: Discussionmentioning

confidence: 73%

“…These findings could provide guidance into the personalization of treatment approaches for HNSCC. We have previously developed a prognostic multivariable survival model using standard and routinely accessible clinical inflammatory markers, including neutrophil and lymphocyte counts, Alb, Hb and LDH values along with p-16 tumor status [15]. Here, we attempt to internally validate the power of our predictive model by expanding our analysis to a larger cohort of 201 patients.…”

Section: Introductionmentioning

confidence: 99%

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Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

et al. 2022

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Background Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. Methods A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. Results 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79. Conclusions Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

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Section: Resultsmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

et al. 2022

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“…However, the benefits of immunotherapy are limited to a small proportion of patients with HNSCC. Therefore, it is important to identify markers that respond well to immunotherapy and further screen appropriate populations for immunotherapy ( 56 , 57 ). PD-L1 has been studied as a potential biomarker in CheckMate 141, KEYNOTE 040, KEYNOTE 048 ( 28 , 30 , 58 ).…”

Section: Immunotherapy In Hnsccmentioning

confidence: 99%

Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus

et al. 2021

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Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking and alcohol consumption are common risk factors of HNSCC; however, an increasing number of cases associated with human papillomavirus (HPV) infection have been reported in recent years. The treatment of HNSCC is integrated and multimodal including traditional surgery, radiotherapy, chemotherapy, and targeted therapy. Since pembrolizumab was approved in 2016, an increasing number of studies have focused on immunotherapy. However, not all of HNSCC patients have a better outcome on immunotherapy. Immunotherapy has been reported to be more effective in HPV-positive patients, but its molecular mechanism is still unclear. Some researchers have proposed that the high proportion of infiltrating immune cells in HPV-positive tumors and the difference in immune checkpoint expression level may be the reasons for their better response. As a result, a series of individualized immunotherapy trials have also been conducted in HPV-positive patients. This paper summarizes the current status of HNSCC immunotherapy, individualized immunotherapy in HPV-positive patients, and immune differences in HPV-positive tumors to provide new insights into HNSCC immunotherapy and try to identify patients who may benefit from immunotherapy.

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“…The use of immune checkpoint inhibitors (ICIs) targeting programmed cell death receptor (PD-1) or its ligand (PD-L1) alone or in combination with chemotherapy is a promising cancer treatment strategy [ 1 , 2 ]. However, as real-world experience confirmed only a minority of patients respond to immunotherapy and have improved long-term survival [ 3 , 4 ]. It is critical to identify reliable predictive biomarkers for selecting patients who can benefit from ICIs.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Nutritional Index Predicts Outcome of PD-L1 Negative and MSS Advanced Cancer Treated with PD-1 Inhibitors

Zhang

Jin

Tang

et al. 2022

BioMed Research International

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Purpose. Tumor mutational burden (TMB), microsatellite instability-high (MSI-H), and expression of programmed death ligand-1 (PD-L1) have emerged as predictive biomarkers for responsiveness to immune checkpoint inhibitors (ICIs) in several cancer types. However, for patients with negative PD-L1 expression, or microsatellite stability (MSS), some cases may experience favorable response to immunotherapy, and there is currently a lack of good relevant predictors. We tried to introduce several peripheral blood markers for predicting treatment outcome and immune-related adverse events (irAEs) in PD-L1 negative and MSS patients. Methods. A retrospective study of 142 PD-L1 negative and MSS patients was carried out. The association of peripheral blood markers including lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin-to-globulin ratio (AGR), prognostic nutrition index (PNI), and other factors with clinicopathological characters and prognosis were assessed by Cox regression and Kaplan-Meier methods. Results. Lower level of PNI and poor performance status (ECOG score of 2) was correlated with significantly shorter overall survival (OS) and worse outcome of ICIs. The multivariate analysis revealed that PNI (for OS HR = 0.465 , 95% CI: 0.236–0.916, p = 0.027 ; for PFS HR = 0.493 , 95% CI: 0.251–0.936, p = 0.031 ) and ECOG score (for OS HR = 4.601 , 95% CI: 2.676–7.910, p < 0.001 ; for PFS HR = 2.830 , 95% CI: 1.707–4.691, p < 0.001 ) were independent prognostic factors for OS and PFS. NLR was related to the onset of irAEs. Conclusions. Pretreatment level of PNI and NLR, beyond PD-L1 expression and MSS, can improve the predictive accuracy for immunotherapy outcomes and has the potential to expand the candidate pool of patients for treatment with ICIs.

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A predictive survival model for patients with head and neck squamous cell carcinoma treated with immune check point inhibitors

Cited by 5 publications

References 40 publications

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus

Prognostic Nutritional Index Predicts Outcome of PD-L1 Negative and MSS Advanced Cancer Treated with PD-1 Inhibitors

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