The impact of comorbidity on the survival of patients with laryngeal squamous cell carcinoma

Abstract Conclusions: In survival analysis, the combined Charlson comorbidity index (CCI) can be considered as a prognostic factor independent of the tumor node metastasis (TNM) classification, tumor stage, and tumor location. Severe comorbidity was the factor that had the greatest impact on prognosis in cases of initial tumor. Objective: To study the influence of comorbidity on the survival of patients undergoing surgery for larynx cancer. Methods: This was a retrospective study of the survival of 231 patients with laryngeal cancer who underwent surgery between 1995 and 2002. The CCI was used to assess comorbidity, the Kaplan-Meier method was used for survival analysis, and the Cox proportional risk regression model was used to identify independent prognostic factors. Results: The multivariate analysis of specific mortality showed that patients classified as having severe comorbidity (CCI) were more likely to die (adjusted hazard ratio (adjHR) 1.85, 95% confidence interval (CI) 1.07-3.17). This difference was more important in patients with early tumor stages than in those with advanced stages.     

Age-adjusted Charlson Comorbidity Index predicts prognosis of laryngopharyngeal cancer treated with radiation therapy

Objectives: To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities.

Methods: This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)-radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared.

Results: Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28–6.49), but not in the surgery group (HR 1.39, 95%CI 0.27–5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p?=?.003).

Conclusion: The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI.     

Comorbidity measurement in patients with laryngeal squamous cell carcinoma

INTRODUCTION: The evaluation of a cancer patient can be affected by many factors. Cancer patients often have other diseases or medical conditions in addition to their cancer. These conditions are referred to as comorbidities. They can influence the treatment option, the rate of complications, the outcome, and can confound the survival analysis. OBJECTIVE: It was the aim of this study to measure comorbidities in patients with laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Ninety adult patients treated for newly diagnosed laryngeal squamous cell carcinoma were studied. We measured comorbid illness applying the following validated scales: the Cumulative Illness Rating Scale (CIRS), the Kaplan-Feinstein Classification (KFC), the Charlson index, the Index of Coexistent Disease (ICED), the Adult Comorbidity Evaluation-27 (ACE-27), the Alcohol-Tobacco-Related Comorbidities Index (ATC), and the Washington University Head and Neck Comorbidity Index (WUHNCI). Survival analysis was performed using the Kaplan-Meier method (with the log-rank test value being used to compare groups). The Cox proportional hazards model was chosen to identify independent prognostic factors. RESULTS: The mean age was 62.3 years. The majority of patients (36.7%) had early tumors. Forty patients were treated by surgery only, while the remaining 49 patients also received postoperative radiation therapy. Only 5 patients (5.6%) were lost to follow-up. Median follow-up time was 42.5 months. The 4-year overall survival was 63%. There was a statistically significant difference between survival rates according to clinical stage (CS I 87.3%, CS II 48.9%, CS III 74.7%, CS IV 23.9%; p < 0.001). Patients treated by surgery only presented a better survival rate (79.6%) than those receiving postoperative radiation therapy (48.9%; p = 0.001). A statistically significant difference in survival rates was also noted when patients were analyzed according to the type of surgical procedure. In a univariate analysis, comorbidity had impact on prognosis, no matter which scale was utilized: CIRS (p = 0.008), ACE-27 (p = 0.010), ATC (p = 0.004), WUHNCI (p = 0.003), Charlson index (p = 0.020), KFC (p = 0.001), and ICED (p = 0.010). However, in the multivariate analysis, only CIRS and TNM staging were identified as independent prognostic factors. CONCLUSION: The comorbidity is an independent prognostic factor in patients with surgically treated laryngeal cancer. In the univariate analysis, all indexes were able to stratify patients. However, in the multiple analysis, only the CIRS was predictive of death. Comorbidities are an important factor in the analysis of overall survival.     

Validation of the Charlson Comorbidity Index in Patients With Head and Neck Cancer: A Multi-institutional Study

Comorbid conditions are medical illnesses that accompany cancer. The impact of these conditions on the outcome of patients with head and neck cancer is well established. However, all of the comorbidity studies in patients with head and neck cancer reported in the literature have been performed using the Kaplan-Feinstein index (KFI), which may be too complicated for routine use. This study was performed to introduce and validate the use of the Charlson comorbidity index (CI) in patients with head and neck cancer and to compare it with the Kaplan-Feinstein comorbidity index for accuracy and ease of use. Study design was a retrospective cohort study. The study population was drawn for three academic tertiary care centers and included 88 patients 45 years of age and under who underwent curative treatment for head and neck cancer. All patients were staged by the KFI and the CI for comorbidity and divided into two groups based on the comorbidity severity staging. Group 1 included patients with advanced comorbidity (stages 2 or 3), and group 2 included those with low-level comorbidity (stages 0 or 1). Outcomes were compared based on these divisions. The KFI was successfully applied to 80% of this study population, and the CI was successfully applied in all cases ( P < 0.0001). In addition, the KFI was found to be more difficult to use than the CI ( P < 0.0001). However, both indices independently predicted the tumor-specific survival ( P = 0.007), even after adjusting for the confounding effects of TNM stage by multivariate analysis. Overall, the CI was found to be a valid prognostic indicator in patients with head and neck cancer. In addition, because comorbidity staging by the CI independently predicted survival, was easier to use, and more readily applied, it may be better suited for use for retrospective comorbidity studies.     

Assessment of apoptosis measured with TUNEL in laryngeal cancer

Programmed cell death is a combined intracellular process. For the activation of apoptosis as proapoptotic genes and antiapoptotic ones are needed as well. There are several methods of apoptosis assessment but in laryngeal cancer prognostic value of apoptotic index is still unclear. 44 patients with laryngeal cancer who received surgical treatment in ENT Department of Medical University of Lodz were analysed. Apoptotic index (AI) was studied by TUNEL assay (TdT-mediated dUTP nick and labeling). There were assessed correlation between AI and primary tumor size and nodal status based on TNM system; local and nodal recurrences; and survival rate after surgical treatment. We observed significant correlation between AI and degree of neoplastic cell polymorphism (p=0,043) and tumor size (T feature) (p=0,01). IA was also significantly correlated with epiglottic site of tumor (p=0,036). There were no correlation between IA and N or M features, local and nodal recurrences or survival rate. Based on these findings we conclude that apoptosis index can be a valuable in prognostic assessment of patients with laryngeal cancer.     

Simple predictors of survival in head and neck squamous cell carcinoma

OBJECTIVE: To develop a simple prognostic survival rule from easily obtained characteristics of patients undergoing potentially curative resection of head and neck squamous cell carcinoma using classification and regression trees. DESIGN: Inception cohort. SETTING: Tertiary care center. PATIENTS: Consecutive patients undergoing resection lasting at least 2 hours, from July 1993 through June 1997. MAIN OUTCOME MEASURE: Survival, age, TNM tumor stage, functional class, systolic and diastolic blood pressure, body mass index, and serum albumin concentration were evaluated as predictors. RESULTS: Four hundred six patients were followed up for 5 to 1446 days (median, 391 days), during which time 172 deaths occurred. Median survival was 687 days. Patients with TNM stage I, II, or III squamous cell carcinoma had a mean survival of 1068 days. Patients with TNM stage IV or recurrent disease were further stratified. Those with a serum albumin concentration less than 3.85 g/dL had a median survival of 404 days (95% confidence interval, 286-532 days), and those with an serum albumin concentration of 3.85 g/dL or above had a median survival of 625 days (95% confidence interval, 536-1032 days). A similar survival was found using age younger than 66.5 years as a predictor instead of serum albumin concentration less than 3.85 g/dL. CONCLUSIONS: At our institution, patients with stage I, II, or III squamous cell carcinoma had a mean survival of approximately 3 years. Those with stage IV or recurrent squamous cell carcinoma could be stratified by either serum albumin concentration or by age into 2 groups with a median survival of 1 or 2 years.     

Applicability of the adult comorbidity evaluation - 27 and the Charlson indexes to assess comorbidity by notes extraction in a cohort of United Kingdom patients with head and neck cancer: a retrospective study

The term comorbidity stands for disease processes that co-exist and are not related to the index disease being studied. Comorbidity in cancer has been shown to be a major determinant in treatment selection and survival. Patients with head and neck cancer can have significant comorbidity owing to the high incidence of tobacco and alcohol abuse. No studies to date have addressed this problem in head and neck cancer patients in the United Kingdom. The applicability of the adult comorbidity evaluation - 27 index (ACE-27) and the Charlson index (CI) to assess the comorbidity burden by retrospective notes review is studied here. Retrospective data collection and completion of a comorbidity index in a United Kingdom setting is feasible. We conclude that the pre-assessment visit is a useful time to record comorbidity and as a significant amount of information required for grading relates to historical items, this is best done using a self-administered patient questionnaire.     

Prognostic importance of harvested lymph node number,metastatic lymph node number,and lymph node ratio in surgically managed laryngeal squamous cell carcinoma

IntroductionLymph node metastasis is a well-known prognostic factor for laryngeal carcinoma. However, current nodal staging systems provide limited information regarding prognosis. Additional parameters should be considered to improve prognostic capacity.ObjectivesTo assess the prognostic values of metastatic lymph node number, ipsilateral/contralateral harvested lymph nodes, and lymph node ratio in patients undergoing surgical treatment of laryngeal squamous cell carcinoma.MethodsSeventy-four patients diagnosed with laryngeal squamous cell carcinoma primarily managed surgically were included in this study. The patients’ pathological and survival data were obtained from their medical records. The effects of harvested lymph nodes and lymph node ratio on disease-free survival, disease-specific survival, and overall survival were analyzed.ResultsIpsilateral, contralateral, and bilateral evaluations of harvested lymph nodes showed no significant associations with prognosis. Lymph node ratio was significantly associated with overall survival when evaluated bilaterally. Metastatic lymph node number showed more suitable stratification than TNM classification.ConclusionsMetastatic lymph node number and bilateral lymph node ratio parameters should be taken into consideration to improve the prognostic capacity of TNM.     

Screening for second primary lung cancer after treatment of laryngeal cancer

OBJECTIVES/HYPOTHESIS: As a result of smoking, patients who have received curative treatment for laryngeal cancer run a high risk of developing lung cancer. Therefore, these patients enter a screening program that aims to detect lung cancer at an asymptomatic stage. The study evaluated whether screening for lung cancer by means of regular chest x-ray examinations contributed to prolonging survival. STUDY DESIGN: A longitudinal follow-up study was performed to analyze the survival of patients who had received curative treatment for squamous cell laryngeal cancer and developed lung cancer during the follow-up period. METHODS: Patients with lung cancer were divided into two groups: 1) patients with asymptomatic screen-detected lung cancer and 2) patients with complaints indicating lung cancer, whose tumor was detected in the interval between screening examinations by chest x-ray films. RESULTS: In the complete group of patients with laryngeal cancer, no prognostic factors could be identified for developing lung cancer. There was no prolongation of survival in the screen-detected asymptomatic lung cancer patients. The median survival of both groups was 56 months (P =.57). The date of detection of the lung cancer was clearly brought forward by screening; a difference of 8 months was found between the median detection date of the two groups (P <.001). There was no difference in tumor-specific mortality between the two groups. CONCLUSION: Screening by chest x-ray examination to detect lung cancer in an asymptomatic stage after curative treatment for squamous cell laryngeal cancer does not improve survival for patients who develop lung cancer.     

免疫相关基因预后模型的构建对喉癌患者预后的影响[论著]

【摘要】 目的　探讨基于生物信息学方法构建免疫相关基因（immune-related genes,IRG）预后模型以准确预测喉癌患者的预后。方法　从癌症基因组图谱（the Cancer Genome Atlas,TCGA）数据库获得111个喉癌组织和12个正常相邻组织之间的差异表达基因（differentially expressed genes,DEG）。利用ImmPort数据库识别出差异表达的IRG。Cox单变量生存分析用于筛选与生存相关的IRG。差异表达的与生存相关的IRG被认为是预后相关的免疫基因。然后构建免疫基因预后模型计算患者风险值,受试者ROC曲线分析验证模型准确性。通过该模型行单因素、多因素独立预后分析证明其独立预测能力。最后分析关键免疫基因与临床病理参数的关联。结果　鉴定喉癌的DEG并筛选出IRG。接着与预后生存时间结合,鉴定8个关键免疫基因（CXCL11、RBP1、AQP9、CYSLTR2、BTC、STC2、UCN和FCGR3B）作为免疫基因预后模型,这种预后模型可以准确的将患者分为高危和低危人群。总体生存分析表明,高危患者的生存时间比低危患者要短（P <0.0001）。模型的ROC曲线下面积为0.810,提示预后模型具有较高的敏感性和准确性。单因素和多因素Cox回归表明其为喉癌患者预后的独立预测因素。此外,我们发现模型中的5个关键基因与临床病理特征显著相关。结论　基于生物信息学方法构建喉癌的免疫相关基因预后模型,发现8个基因有助于预测喉癌患者的预后,其中5个与临床病理特征显著相关。     

Survival of patients with laryngeal cancer and some prognostic factors

Tumour growth and its progression to a metastatic phenotype involves a serious of genetic events with abnormal activation of oncogenes or inactivation of tumour suppressor genes and others genes connected with proliferation, apoptosis and neovascularisation. The aims of the study were to determine the possible prognostic value of angiogenesis, proliferation index Ki67, p53 and bcl-2 proteins expression in patients with laryngeal cancer. The group of 151 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. Paraffin--embedded tissue sections from each case were stained with a monoclonal antibody raised against FVIII antigen, p53 and bcl-2 proteins and Ki67 proliferation antigen using a peroxidase labelled streptavidin--biotin kit in standard immunohistochemistry techniques. In univariate analysis: staging IV, tumour size T4, nodal metastasis N2 and N3, local and nodal recurrences, high expression of Ki67 and P53, high (over median) IA measured as number of microvessels with FVIII expression were significantly associated with shortened overall survival. Disease-free survival was related to: proliferation index Ki67, expression of P53 protein and angiogenesis measured as microvessels density with expression of FVIII antigen. In multivariate analysis the most important death risk factors for overall survival were: tumour size, nodal metastasis, local and nodal recurrences, P53 protein expression and IA measured as number of microvessels with FVIII expression. In multivariate analysis of disease-free survival only P53 protein expression, proliferative index Ki67 and expression of FVIII had independent prognostic value. Intensity of angiogenesis, proliferation index of Ki67 antigen and expression of P53 protein were independent predictors of patients with laryngeal cancer outcome. In contrary Bcl2 protein seems to be useless in these patients.     

喉癌组织中缺氧诱导因子1α和表皮生长因子受体的表达与微血管密度的关系

目的 分析喉癌组织中缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)、表皮生长因子受体(epidermal growth factor receptor,EGFR)的表达与CD105标记计数微血管密度(micro vessel density,MVD)的关系及其在评价喉癌生物学行为和预后中的价值.方法 回顾性分析1990年1月至2002年1月91例喉癌患者临床病理资料及随访结果,免疫组化法检测肿瘤组织中HIF-1α、EGFR的表达,CD105标记肿瘤组织中微血管并计数MVD.结果 HIF-1α的表达与肿瘤大小、TNM分期、T分期、淋巴转移和病理分级有关(P值均<0.05);EGFR表达与TNM分期、淋巴转移、病理分级和复发有关(P值均<0.05);MVD与喉痛部位分型、TNM分期、T分期、淋巴转移、远处转移和病理分级有关(P值均<0.05).HIF-1α、EGFR表达水平与MVD有关(F值为7.644和5.197,P值为0.001和0.025).HIF-1α与EGFR表达的相关分析差异有统计学意义(r=0.238,P=0.007).患者3年和5年生存率为56.1%和44.2%,Log-rank法单因素生存分析表明喉癌部位分型、TNM分期、HIF-1α和EGFR的表达与患者预后有关(P值均<0.05);Cox比例风险模型分析显示TNM分期和EGFR的表达为影响喉癌患者预后的独立危险因素(P值分别为0.049和0.041,RR值分别为1.300和2.417).结论 在喉癌发生和进展过程中存在HIF-1α与EGFR的异常表达,且对调节肿瘤血管生成有一定的作用,并与肿瘤的生物学行为和预后有关.     

下咽癌共病食管癌的高危因素及预后分析

目的 探讨下咽癌共病同时性食管癌的高危因素及预后。 方法 2011年1月至2014年3月诊治的200例下咽癌患者作为研究对象,回顾性分析患者的一般资料、肿瘤信息和随访情况。先对可能影响下咽癌共病同时性食管癌的危险因素进行单因素分析,组间比较采用卡方检验,进一步将有统计学差异的因素纳入Logistic回归分析。生存率的分析采用Kaplan-Meier法。 结果 单因素分析发现,年龄(<55岁)、男性、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的高危因素(P<0.05)。多因素分析结果显示,年龄(<55岁)、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的独立危险因素(P<0.05)。200例下咽癌患者中位生存时间仅为37.5个月,5年生存率仅为36.7%。56例下咽癌共病同时性食管癌患者中位生存时间为24.8个月,低于下咽癌不伴同时性食管癌患者(P<0.05)。早期食管癌(0+Ⅰ期)患者的中位生存时间为29.2个月,明显高于进展期食管癌(Ⅱ+Ⅲ期)的15.8个月,差异有统计学意义(P<0.05)。 结论 下咽癌共病同时性食管癌患者的生存时间较低。年龄(<55岁)、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的独立危险因素,临床上应该针对这些高危因素进行早期干预。     

Head and neck cancer and ageing: a retrospective study in 438 patients

To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non-elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post-operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor.     

Using comorbidity indexes to predict costs for head and neck cancer

OBJECTIVE: To determine whether the general Charlson Comorbidity Index (CCI) and the head and neck cancer-specific Washington University Head and Neck Cancer Comorbidity Index (WUHNCCI) were useful for predicting cost of treatment for elderly patients with head and neck cancer. DESIGN: Retrospective, observational study. PATIENTS: A total of 1780 Medicare patients with head and neck cancer, who were treated between 1984 and 1994, were analyzed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. MAIN OUTCOME MEASURES: Total Medicare payments were accumulated for each patient up to 1 and 5 years. Linear regression was used to estimate the impact of the comorbidity indexes on costs, controlling for demographics, site, stage, and treatment modality. RESULTS: Neither the WUHNCCI nor the CCI was significantly associated with 1-year costs. However, the effect of the WUHNCCI on 5-year costs was statistically significant (P<.001). A 1-point increase in the WUHNCCI from 4 to 5 was associated with an increase in 5-year costs of $2105. A 1-point increase in the WUHNCCI from 9 to 10 was associated with an increase in 5-year costs of $2837. CONCLUSION: These results suggest that comorbidity indexes for head and neck cancer may be useful for prognostication of patient outcomes and predicting costs.     

喉癌组织中细胞黏附分子和尿激酶型纤溶酶原激活剂的表达及在预后评估中的价值

目的 研究喉癌组织中细胞黏附分子E-cadherin(ECD)和尿激酶型纤溶酶原激活剂(urokinase-type plasminogen activator,uPA)的表达及其在喉癌患者临床预后评估中的价值.方法 采用免疫组化Envision二步法分别检测ECD、uPA在51例喉癌切除标本组织中的表达情况并结合临床随访,分析其与临床病理参数及患者预后的关系.结果 ECD在51例喉癌中阴性表达24例(47.1%),uPA阳性表达26例(51.0%),ECD的表达缺失或下降、uPA的高表达与喉癌的淋巴转移有关(X~2值分别为5.545和5.790,P值分别为0.019和0.016).ECD阳性者生存率为74.1%,ECD阴性者生存率为54.2%,两者差异无统计学意义(X~2=2.534,P＞0.05).uPA阳性者生存率为50.0%,uPA阴性者生存率为80.0%,两者差异有统计学意义(X~2=6.259,P＜0.05).按照二者表达的不同分为4组:ECD(-)/uPA(-)、ECD(+)/uPA(-)、ECD(-)/uPA(+)、ECD(+)/uPA(+),ECD(-)/uPA(+)组与另外3组比较,有明显的淋巴转移倾向(X~2=11.937,P=0.008).ECD(+)/uPA(-)组生存率为78.6%,ECD(-)/uPA(+)组患者生存率为30.8%,两组差异有统计学意义(X~2=6.559,P=0.01).Cox多因素回归分析显示,ECD和uPA的表达及临床分期是影响患者预后的独立因素.结论 ECD和uPA表达的联合分析可有助于评估喉癌发生转移的危险性,并有助于为评估临床预后提供参考.     

Prognostic significance of nodal ratio in cutaneous squamous cell carcinoma of the head and neck

The TNM classification is not specific for head and neck skin cancer and makes no allowance for disease extent. Studies have shown that the relative number of metastatic-to-examined lymph nodes, termed the Nodal ratio, is a reliable independent prognosticator in several types of cancer. The study was designed as a retrospective analysis in a university affiliated tertiary care center setting. The files of all patients (n = 71) with cutaneous head and neck squamous cell carcinoma and regional lymph node metastasis who attended a tertiary medical center between 1990 and 2008 were reviewed for clinical variables and outcome, and Nodal ratio was calculated. Data were analyzed for impact on survival. On multivariate analysis Nodal ratio and age were found to be significant predictors of overall survival. The N-ratio was the only significant predictor of disease-specific survival. Age, type of treatment (selective/modified neck dissection), pathologic N stage, and radiotherapy had no effect. The Nodal ratio is a potentially valuable prognostic index in cutaneous squamous cell carcinoma. The minimal number of nodes that need to be excised has to be determined.     

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.