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1.
Head Neck ; 45(8): 2028-2039, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37345665

ABSTRACT

BACKGROUND: The comparative impact of histologic variants and grade has not been well described. METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.


Subject(s)
Adenoma, Pleomorphic , Carcinoma, Acinar Cell , Carcinoma, Adenoid Cystic , Carcinoma, Mucoepidermoid , Salivary Gland Neoplasms , Humans , Salivary Gland Neoplasms/pathology , Adenoma, Pleomorphic/pathology , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Acinar Cell/pathology
2.
Laryngoscope ; 133(7): 1660-1666, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36054029

ABSTRACT

BACKGROUND: Elective neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery, based largely on historical series. It is unclear if this is necessary for all patients in the modern era. METHODS: Patients with cN0 oropharynx, larynx, and hypopharynx cancers diagnosed from 2010-2015 undergoing primary surgery were identified in the National Cancer Data Base. RESULTS: Inclusion criteria were met by 4117 cN0 patients. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, p < 0.001). Histologic grade strongly predicted pN+ (OR 2.58, 95% CI 1.88-3.59, p < 0.001). A nomogram predicted less than 10% of cN0 patients had pN+ risk <15%. CONCLUSION: LVI and grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancer. Even in the modern era, pN+ rates warrant neck dissection for cN0 patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1660-1666, 2023.


Subject(s)
Laryngeal Neoplasms , Humans , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Pharynx/pathology , Lymphatic Metastasis/pathology , Neck Dissection , Lymph Nodes/pathology , Neoplasm Staging , Retrospective Studies
3.
J Natl Cancer Inst ; 114(7): 1003-1011, 2022 07 11.
Article in English | MEDLINE | ID: mdl-35311991

ABSTRACT

BACKGROUND: Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors. METHODS: We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses. RESULTS: Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites. CONCLUSIONS: Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors.


Subject(s)
Lymph Nodes , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Staging , Prognosis , Reproducibility of Results , Retrospective Studies
4.
Cancer ; 127(10): 1590-1597, 2021 05 15.
Article in English | MEDLINE | ID: mdl-33595897

ABSTRACT

BACKGROUND: Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification. METHODS: Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema. RESULTS: Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+. CONCLUSION: HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis. LAY SUMMARY: The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy.


Subject(s)
Carcinoma , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma/pathology , Carcinoma/virology , Humans , Neoplasm Staging , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/epidemiology , Prognosis
5.
Head Neck ; 43(4): 1105-1115, 2021 04.
Article in English | MEDLINE | ID: mdl-33300641

ABSTRACT

BACKGROUND: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain. METHODS: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed. RESULTS: Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate-grade (hazard ratio [HR] 1.16, 95% CI 1.07-1.26, P < .001) and high-grade (HR 1.38, 95% CI 1.26-1.52, P < .001) tumors had worse survival than low-grade tumors. This magnitude was comparable to other well-established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(-) oropharynx cancer. CONCLUSIONS: The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Humans , Prognosis , Squamous Cell Carcinoma of Head and Neck
6.
JAMA Oncol ; 6(10): 1555-1562, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32816023

ABSTRACT

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data. Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer. Design, Setting, and Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020. Main Outcomes and Measures: Overall survival. Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10). Conclusions and Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.


Subject(s)
Oropharyngeal Neoplasms/surgery , Robotic Surgical Procedures/methods , Squamous Cell Carcinoma of Head and Neck/surgery , Adult , Aged , Female , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Staging , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Propensity Score , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology
7.
J Geriatr Oncol ; 11(7): 1108-1114, 2020 09.
Article in English | MEDLINE | ID: mdl-32222347

ABSTRACT

OBJECTIVE: Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention of readmission. MATERIALS AND METHODS: Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis. RESULTS: This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days. CONCLUSION: This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission.


Subject(s)
Neoplasms , Patient Readmission , Aged , Case-Control Studies , Humans , Neoplasms/therapy , Patient Discharge , Retrospective Studies , Risk Factors
8.
Cancer ; 126(1): 58-66, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31536144

ABSTRACT

BACKGROUND: Patients with clinical stage I human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy. METHODS: The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV-positive OPSCC (AJCC seventh edition stage T1-2N0-2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy. RESULTS: The current analysis included 4473 patients with HPV-positive stage I OPSCC with a median follow-up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645-0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node-positive stage I disease (stage III-IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557-0.835 [P < .001]), but not for patients with N0 disease (stage I-II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011-2.681 [P = .05]). Similar results were noted among propensity score-matched cohorts. CONCLUSIONS: Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node-positive, but not lymph node-negative, AJCC eighth edition stage I HPV-positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients.


Subject(s)
Oropharyngeal Neoplasms/drug therapy , Papillomavirus Infections/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Aged , Chemoradiotherapy/adverse effects , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/virology , Papillomaviridae/pathogenicity , Papillomavirus Infections/pathology , Papillomavirus Infections/radiotherapy , Papillomavirus Infections/virology , Proportional Hazards Models , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/virology , Treatment Outcome
9.
Oral Oncol ; 99: 104472, 2019 12.
Article in English | MEDLINE | ID: mdl-31704556

ABSTRACT

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has dramatically increased in incidence and prevalence among patients aged 70 and older. There are virtually no data regarding outcomes in this population, and thus optimal therapy, including the role of chemotherapy for those undergoing radiotherapy (RT), remains unclear. METHODS: The National Cancer Database was queried for older adults (defined as age 70 years and older) with locally advanced OPSCC (cT1-2N1-3, cT3-4N0-3) diagnosed from 2010 to 2014 with known HPV-status undergoing definitive RT alone or chemoradiation (CRT). RESULTS: Overall, 1,965 older adults with locally advanced OPSCC met inclusion criteria, including 1,141 HPV-positive (58%) and 824 HPV-negative (42%) patients. 1,211 patients (62%) received CRT. In multivariable analysis, CRT was associated with improved survival in older patients when compared to RT alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.64-0.86, P < 0.001). CRT was associated with improved survival in both HPV-positive (HR = 0.80, 95% CI: 0.64-1.00, P = 0.05) and HPV-negative (HR = 0.69, 95% CI: 0.56-0.85, P < 0.001) subgroups. There was no significant interaction between HPV status and the impact of CRT on survival (P interaction = 0.57). CONCLUSIONS: Despite the radiosensitivity of HPV-positive OPSCC and the challenges in delivering CRT to older adults, CRT was associated with improved survival in older patients with HPV-positive OPSCC, similar in magnitude to the benefit in HPV-negative patients. As the incidence of HPV-positive OPSCC in older patients continues to increase, further studies are needed to investigate optimal therapeutic strategies in this population.


Subject(s)
Chemoradiotherapy/methods , Oropharyngeal Neoplasms/drug therapy , Papillomaviridae/pathogenicity , Papillomavirus Infections/complications , Aged , Female , Humans , Male , Oropharyngeal Neoplasms/mortality , Prevalence
10.
Cancer ; 124(15): 3154-3162, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29742280

ABSTRACT

BACKGROUND: Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC. METHODS: Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival. RESULTS: Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements. CONCLUSIONS: Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when considering survival burden. Cancer 2018. © 2018 American Cancer Society.


Subject(s)
Head and Neck Neoplasms/epidemiology , Survival Analysis , Time-to-Treatment , Adult , Aged , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Humans , Male , Medicare , Middle Aged , Proportional Hazards Models , Radiotherapy/trends , Risk Factors , Survival Rate , United States
11.
JAMA Oncol ; 4(7): 985-989, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29192305

ABSTRACT

Importance: Nodal staging for laryngohypopharyngeal cancers is based primarily on size and laterality, with less value placed on absolute number of metastatic lymph nodes (LNs). We are aware of no studies to date that have specifically addressed the prognostic effect of quantitative nodal burden in larynx or hypopharynx malignancies. Objective: To assess the independent impact of quantitative metastatic LN burden on mortality risk. Design, Setting, and Participants: Univariate and multivariable models were constructed to evaluate the association between patients' number of metastatic LNs and their survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Participants were patients with squamous cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection for curative intent at a US hospital between 2004 and 2013, as identified in the National Cancer Database. A neck dissection of a minimum of 10 LNs was required. Main Outcomes and Measures: Overall survival. Results: Overall, 8351 cases were included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated continuously without plateau as number of metastatic nodes increased, with the hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; P < .001) most pronounced up to 5 positive LNs. Extranodal extension was also associated with increased mortality (HR, 1.34; 95% CI, 1.13-1.59; P < .001). Increasing number of nodes examined was associated with improved survival, albeit to a lesser degree (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; P < .001) and without a detectable change point. Other nodal factors, including nodal size, contralateral LN involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not associated with mortality in multivariable models when accounting for number of positive LNs. A novel, parsimonious nodal staging system derived by recursive partitioning analysis exhibited greater concordance with survival than the TNM staging system outlined in the American Joint Committee on Cancer's AJCC Staging Manual, 8th edition. Conclusions and Relevance: The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.


Subject(s)
Hypopharyngeal Neoplasms/complications , Laryngeal Neoplasms/complications , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Female , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Male , Middle Aged , Survival Analysis
12.
J Clin Oncol ; 35(31): 3601-3609, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28880746

ABSTRACT

Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.


Subject(s)
Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Lymph Nodes/pathology , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/surgery , Female , Head and Neck Neoplasms/surgery , Humans , Kaplan-Meier Estimate , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Models, Statistical , Mouth Neoplasms/surgery , Neoplasm Staging , Prognosis , Proportional Hazards Models , Squamous Cell Carcinoma of Head and Neck , Tumor Burden
13.
Cancer ; 123(23): 4583-4593, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28817183

ABSTRACT

BACKGROUND: There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. METHODS: This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. RESULTS: In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P < .001). Improved survival was associated only with patients receiving high-intensity local treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P < .001) in comparison with more than 6 months after the diagnosis (AHR, 0.622; 95% CI, 0.561-0.689; P < .001) in the multivariate analysis. A benefit was seen in all subgroups, in landmark analyses of 1-, 2-, and 3-year survivors, and when adjusting for the number and location of metastatic sites. CONCLUSIONS: Aggressive local treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society.


Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Databases, Factual , Head and Neck Neoplasms/therapy , Aged , Carcinoma, Squamous Cell/secondary , Female , Follow-Up Studies , Head and Neck Neoplasms/pathology , Humans , Male , Neoplasm Staging , Prognosis , Propensity Score , Radiotherapy Dosage , Retrospective Studies , Survival Rate
14.
Cancer ; 123(20): 3933-3942, 2017 Oct 15.
Article in English | MEDLINE | ID: mdl-28640546

ABSTRACT

BACKGROUND: The treatment of head and neck cancers is complex and associated with significant morbidity, requiring multidisciplinary care and physician expertise. Thus, facility characteristics, such as clinical volume and academic status, may influence outcomes. METHODS: The current study included 46,567 patients taken from the National Cancer Data Base who were diagnosed with locally advanced invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx and were undergoing definitive radiotherapy. High-volume facilities (HVFs) were defined as the top 1% of centers by the number of patients treated from 2004 through 2012. Multivariable Cox regression and propensity score matching were performed to account for imbalances in covariates. RESULTS: The median follow-up was 55.1 months. Treatment at a HVF (hazard ratio, 0.798; 95% confidence interval, 0.753-0.845 [P<.001]) and treatment at an academic facility (hazard ratio, 0.897; 95% confidence interval, 0.871-0.923 [P<.001]) were found to be independently associated with improved overall survival in multivariable analysis. In propensity score-matched cohorts, the 5-year overall survival rate was 61.6% versus 55.5% for patients treated at an HVF versus lower-volume facilities, respectively (P<.001). Similarly, the 5-year overall survival rate was 52.3% versus 49.7% for patients treated at academic versus nonacademic facilities (P<.001). Analysis of facility volume as a continuous variable demonstrated continual improvement in survival with an increased number of patients treated. The impact of facility volume and academic designation on survival was observed when using a variety of thresholds to define HVF, and across the vast majority of subgroups, including both oropharyngeal and nonoropharyngeal subsites. CONCLUSIONS: Patients with locally advanced head and neck squamous cell carcinoma who are undergoing curative radiotherapy at HVFs and academic centers appear to have improved survival. Cancer 2017;123:3933-42. © 2017 American Cancer Society.


Subject(s)
Academic Medical Centers , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Hospitals, High-Volume , Radiotherapy , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Databases, Factual , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Propensity Score , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival Rate
15.
J Natl Compr Canc Netw ; 11(9): 1040-4, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-24029120

ABSTRACT

This case report describes the rare occurrence of a T790M resistance mutation found in a central nervous system (CNS) parenchymal metastasis. A concomitant squamous histology transformation in a lung non-T790M-resistant metastasis is also described. The authors hypothesize that this CNS resistance and histology transformation may have resulted from intermittent use of erlotinib treatment. This case report emphasizes the complexities of using erlotinib in the induction setting.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/etiology , ErbB Receptors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neoplasms, Second Primary/etiology , Antineoplastic Agents/therapeutic use , Brain Neoplasms/diagnosis , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/diagnosis , Cell Transformation, Neoplastic/drug effects , Cell Transformation, Neoplastic/genetics , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride , Female , Humans , Lung Neoplasms/drug therapy , Middle Aged , Neoplasms, Second Primary/diagnosis , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use
16.
Expert Opin Investig Drugs ; 22(6): 795-801, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23594190

ABSTRACT

INTRODUCTION: Dasatinib is a novel tyrosine kinase inhibitor with activity against the Src family kinases. The Src pathway is active in breast cancer and has been shown to promote cell proliferation, invasiveness, and metastases. Preclinical data support the use of dasatinib to inhibit breast cancer cell growth, modulate hormone and EGFR signaling, and alter cell migration. AREAS COVERED: This article details the preclinical data supporting dasatinib's use in breast cancer treatment. Additionally, Phase I/II studies that have tested dasatinib as a single agent and in combination with chemotherapy and antihormonal agents are discussed. EXPERT OPINION: Phase I/II studies to date have shown only limited responses to dasatinib among breast cancer patients. Dasatinib has no current role in the treatment of breast cancer, and its future is uncertain. No specific subset of patients has been identified which preferentially responds to treatment. Studies are under way to identify specific molecular markers that might predict response to dasatinib.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Pyrimidines/pharmacology , Thiazoles/pharmacology , Animals , Breast Neoplasms/pathology , Cell Movement/drug effects , Clinical Trials as Topic , Dasatinib , Drug Evaluation, Preclinical , ErbB Receptors , Female , Humans , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , src-Family Kinases/antagonists & inhibitors
18.
J Oncol Pract ; 7(2): 103-10, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21731518

ABSTRACT

BACKGROUND: Coordination of care has grown in importance with the advent of new modalities of treatment that require specialized expertise. In cancer care, multidisciplinary approaches have shown improvements in quality of care. Tumor boards may provide a mechanism for improving coordination of care. We evaluated physician and practice characteristics that predict frequency of tumor board attendance. MATERIALS AND METHODS: This cross-sectional study used data obtained by surveying physicians of a population-based sample of women with incident breast cancer. Physicians were queried regarding tumor board attendance, specialty [medical oncologist (MO), radiation oncologist (RO), surgeon at a hospital with American College of Surgeons accreditation (ACOSSg) and surgeon without such affiliation (non-ACOSSg)], physician characteristics (gender, race/ethnicity, teaching involvement, patient volume, ownership interest) and practice setting (type, size, reimbursement method). Univariate, bivariate, and multivariate analyses were performed for the dependent variable characterizing provider report of frequency of tumor board attendance. RESULTS: Most surveyed physicians (83%) report attending tumor board weekly (58%) or monthly (25%). Specialty and higher patient volumes are significant predictors of more frequent attendance. Compared with the most prevalent specialty category (low-volume ACOSSgs), high-volume MOs attend more frequently (P = .01) and low volume non-ACOSSgs attend less frequently (P = .00). CONCLUSIONS: Tumor board provides a structure for engaging providers in discussion of cancer cases that is designed to enhance quality of care. Tumor board agendas and formalized institution-wide policies could be designed to engage low-frequency attendees as a means to improve quality measures, promote multidisciplinary care, and potentially improve health outcomes.

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