Impact of stage, management and recurrence on survival rates in laryngeal cancer.
ABSTRACT: A retrospective, longitudinal study of 1,616 patients with primary laryngeal squamous cell carcinoma (LSCC) at a single center in Norway during 1983-2010 was undertaken to investigate overall survival, disease specific survival, disease-free survival, prognostic factors for overall survival, and impact of recurrence among all-stage laryngeal cancer patients over 15 years' follow-up. The prognostic impact of gender, age, smoking/alcohol, subsite, tumour, node and metastasis staging, period and modality of treatment were evaluated using Kaplan-Meier and Cox proportional hazard analyses. The importance of recurrence on survival was assessed based on case fatality rates. Five-year overall survival was 56.8%, 64.0% and 38.8%, and disease-specific survival was 80.2%, 87% and 61.6%, respectively, for the entire cohort and for glottic and supraglottic LSCC. Old age, advanced-stage LSCC and supraglottic cancer were associated with lower overall survival. The risk of disease-specific death plateaued after five years and varied significantly by subsite. Multivariate analysis of glottic LSCC revealed that surgical treatment improved overall survival, whereas old age, alcohol, T3-T4 status, positive N-status and no treatment were associated with worse survival. In supraglottic LSCC, age, alcohol, and positive N-status had a significant impact on overall survival by multivariate analysis. Five-year overall survival and disease-specific survival among patients with recurrent disease were 34% and 52%, respectively. In conclusion, marked difference in overall survival between glottic and supraglottic LSCC underline the importance of subsite-specific survival analysis. T-status and primary surgical management is essential only for glottic LSCC, emphasizing the importance of correct disease classification. Inferior outcomes in supraglottic LSCC are associated with old age, positive N-status, and improved follow-up routines are necessary. Primary tumor control is essential since recurrence impairs survival considerably in all subsites. The potential benefit of a primary surgical approach towards T3 LSCC awaits further investigation.
Project description:A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2-T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma.
Project description:OBJECTIVE:The aim of this study is to compare pre-therapeutic staging of the loco-regional lymphatic basin and subsequent surgical management in cN0 versus cN+?hypopharyngeal and laryngeal cancer patients. METHODS:We analyzed all hypopharyngeal and laryngeal carcinoma patients treated surgically at a single quaternary medical care and cancer center between 2004 and 2014. We established two groups for patients who underwent neck dissection comparing patients with a low LNR (lymph node ratio) to one with a high LNR. Regarding the cN0 cohort, elective neck dissection was evaluated as a secondary predictor variable. Comorbidities, such as anemia and renal insufficiency, were analyzed as potentially influencing disease-free (DFS) and overall survival (OS). RESULTS:A total of 310 patients (185 glottic and 125 supraglottic/hypopharyngeal carcinoma) were included. Pre-therapeutic neck MRI-/CT-scan and concomitant neck ultrasound revealed cN+?status in 144 patients resulting in a significant over-staging in 63 patients (44%) who were rated as being pN0 after histological examination. 166 patients were staged cN0 and 21 underwent elective neck dissection (11 local advanced glottic and 10 supraglottic/hypopharyngeal carcinoma). Two cN0 patients showed occult cervical lymph node metastases (10%). Furthermore, we could detect a significant negative impact of the LNR divided by the number of dissected lymph nodes and OS. CONCLUSION:The pre-therapeutic clinical evaluation of lymphatic outgrowth is over-staged. OS decreases with increasing LNR divided by the number of dissected lymph nodes. Renal insufficiency and anemia are significant negative factors, decreasing both OS and DFS.
Project description:Background:Laryngeal squamous cell carcinoma (LSCC) in young patients was reported to be more aggressive and associated with poorer survival than in older patients. However, very few studies contained sufficient cases to permit meaningful statistical analysis. It is still unknown whether less aggressive method like radical radiotherapy (RT) is comparable to total laryngectomy (TL) in survival rate among young patients. Methods:This study extracted patient data from the surveillance, epidemiology, and end results database from 2004 to 2015. The findings for 304 patients (1.2%) below the age of 40 were compared with those for 24,827 patients (98.8%) aged 40 or older. Results:The younger cohorts contained a higher proportion of female patients (33.6% vs. 19.1%, respectively), had more cases of glottic involvement (64.5% vs. 53.1%), and were less likely to have distant metastasis (0.7% vs.3.2%). A total of 5-year overall survival and cancer-specific survival rates (CSS) in the younger patients were 86.3% and 88.8%, respectively, significantly better than for older patients (53.8% and 67.6%). Significant differences were still observed when stratified for tumor stage (stage I-IV). The negative independent prognostic factors in younger patients were advanced tumor stage, degree of nodal involvement, and status of distant metastasis. Treatment with surgery and/or RT all produced excellent outcomes in stage I-IV diseases, and radical RT resulted in survival rates equal to those for TL in locally advanced LSCC among young patients (5-year CSS: 90% vs. 91.5%, p = 0.99). Conclusion:LSCC is less aggressive and has significantly better survival in younger patients. For younger patients, advanced nodal involvement is the most important independent prognostic factor, and larynx preservation is comparable to TL in survival rate.
Project description:Objectives:The aim of this study was to establish the prognostic value of the epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on local control in patients with early stage supraglottic laryngeal squamous cell carcinoma (LSCC) treated with radiotherapy only. Study design:Retrospective cohort study. Methods:Immunohistochemical staining for EGFR and PTEN was performed on pretreatment biopsies of a selected well-defined homogeneous group of 52 patients with T1-T2 supraglottic LSCC treated with radiotherapy between 1990 and 2008. Kaplan-Meier analysis and univariate and multivariate Cox Regression analyses were performed to correlate clinical data and expression levels of EGFR and PTEN with local control. Results:Kaplan-Meier survival analysis and Cox Regression analysis showed a significant association between PTEN expression and local control (hazard ratio [HR] = 3.26, 95% confidence interval [CI] = 1.14-9.33, P = .027) and between lymph node status and local control (HR = 3.60, 95% CI = 1.26-10.31, P = .017). Both were independent prognostic factors in a multivariate analysis (HR = 3.28, 95% CI = 1.14-9.39, P = .027 and HR = 3.62, 95% CI = 1.26-10.37, P = .017, respectively). There was no significant association between EGFR expression and local control (HR = 1.32, 95% CI = 1.17-10.14, P = .79). Conclusion:This study showed an association between both high PTEN expression and the presence of lymph node metastasis and deteriorated local control in early stage supraglottic LSCC treated with radiotherapy. Level of Evidence:NA.
Project description:Transoral laser microsurgery (TLM) is an accepted and effective treatment strategy for supraglottic carcinomas. Early supraglottic carcinoma has excellent outcomes independently of the treatment approach. The role of TLM for the treatment of locally advanced tumors is debated. Particularly, the functional outcomes after TLM have to be proven by functional assessment of large cohorts of patients. This study analyzes the oncologic and functional outcomes after TLM for supraglottic carcinomas.Ninety-one patients with pT1-pT4a supraglottic carcinomas treated between January 2002 and December 2012 were analyzed. Distribution of tumors (UICC 2010) was 11 patients with pT1, 31 patients with pT2, 36 patients with pT3, and 13 patients with pT4a tumors. Node status was positive in 40 (43.6%) patients; 61 (67.1%) patients had stage III or IVa disease. Local control and survival were estimated using the Kaplan-Meier method. For the assessment of functional outcomes, the MD Anderson Dysphagia Inventory (MDADI), the Voice Handicap Index-10 (VHI-10), and the performance status scale for head and neck cancer [Performance Status Scale for Head and Neck (PSS-HN)] were used.The median age was 62 years (range, 33-88 years). Fourteen (15.4%) patients developed a local or locoregional recurrence. The 5-year local control rate and 5-year ultimate local control rate were 72 and 92%, respectively. The 5-year overall survival rate was 63%. Twelve (13.2%) patients needed temporary tracheostomy. Sixty-eight (74.0%) patients had a nasogastric feeding tube post-operatively. At 1-year post-operative follow-up, only three patients were PEG dependent. The median VHI-10 score was 35, the median MDADI composite score was 80, and the median score of the domain "normalcy of diet" in the PSS-HN was 91.The oncologic outcomes are comparable to the results of open surgery for early and advanced supraglottic carcinomas. Functional swallowing outcome is superior to open surgery and to concomitant chemoradiation. Patients treated with TLM perceive low levels of voice- and swallowing-related quality of life impairment.
Project description:BACKGROUND:Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS:All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS:36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS:The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.
Project description:Background:Both radiotherapy and surgery are now recommended for early stage glottic laryngeal squamous cell carcinoma (LSCC), and both have their own advantages in patients with different characteristics. For each patient, it is hard to determine whether radiotherapy or surgery is more appropriate. Methods:Patients with T1-2N0M0 glottic LSCC who received radiotherapy or surgery in the 2004-2016 SEER database were reviewed, then randomly divided into training and validation cohorts. Propensity score matching was used to eliminate the baseline variations, and competing risk analyses helped to exclude the effects of other causes of death. Based on univariate and multivariate analyses, we built two nomograms to visually predict the survival of each patient with different characteristics who received radiotherapy or surgery, then validated the accuracy in both training and validation cohorts. Using nomogramEx, we quantified the algorithms of the nomograms and put the nomograms on the websites. Results:A total of 6538 patients in the SEER database were included. We found that therapy (p = 0.004), T stage (p < 0.001), age (p < 0.001), race (p < 0.044), grade (p = 0.001), and marital status (p < 0.001) were independent prognostic factors. Two nomograms were built to calculate the survival for each patient who received radiotherapy (C-index = 0.668 ± 0.050 in the training cohort and 0.578 ± 0.028 in the validation cohort) or underwent surgery (C-index = 0.772 ± 0.045 in the training cohort and 0.658 ± 0.090 in the validation cohort). Calibration plots showed the accuracy of the nomograms. Using the nomograms, we found that 3872 patients (59.22%) had no difference between the two therapies, 706 patients (10.80%) who received radiotherapy had better survival outcomes, and 1960 patients (29.98%) who underwent surgery had better survival outcome. Conclusion:Nomograms were used to comprehensively calculate independent factors to determine which treatment (radiotherapy or surgery) is better for each patient. A website was used to offer guidance regarding surgery or radiation for patients and physicians.
Project description:The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.
Project description:Laryngeal squamous cell carcinoma (LSCC) is a genetically complex tumor type and one of the leading causes of cancer-associated disability and mortality. Genetic instability, such as chromosomal instability, is associated with the tumorigenesis of LSCC. Copy number variations (CNVs) have been demonstrated to contribute to the genetic diversity of tumor pathogenesis. Comparative genomic hybridization (CGH) has emerged as a high-throughput genomic technology that facilitates the aggregation of high-resolution data of cancer-associated genomic imbalances. In the present study, a total of 38 primary supraglottic LSCC cases were analyzed by high-resolution array-based CGH (aCGH) to improve the understanding of the genetic alterations in LSCC. Additionally, integration with bioinformatic analysis of microarray expression profiling data from the Gene Expression Omnibus (GEO) database provided a fundamental method for the identification of putative target genes. Genomic CNVs were detected in all cases. The size of net genomic imbalances per case ranged between a loss of 682.3 Mb (~24% of the genome) and a gain of 1,958.6 Mb (~69% of the genome). Recurrent gains included 2pter-q22.1, 3q26.1-qter, 5pter-p12, 7p22.3p14.1, 8p12p11.22, 8q24.13q24.3, 11q13.2q13.4, 12pter-p12.2, 18pter-p11.31 and 20p13p12.1, whereas recurrent losses included 3pter-p21.32, 4q28.1-q35.2, 5q13.2-qter, 9pter-p21.3 and monosomy 13. Gains of 3q26.1-qter were associated with tumor stage, poor differentiation and smoking history. Additionally, through integration with bioinformatic analysis of data from the GEO database, putative target oncogenes, including sex-determining region Y-box 2, eukaryotic translation initiation factor 4 gamma 1, fragile X-related gene 1, disheveled segment polarity protein 3, defective n cullin neddylation 1 domain containing 1, insulin like growth factor 2 mRNA binding protein 2 and CCDC26 long non-coding RNA, and tumor suppressor genes, such as CUB and sushi multiple domains 1, cyclin dependent kinase inhibitor 2A, protocadherin 20, serine peptidase inhibitor Kazal type 5 and Nei like DNA glycosylase 3, were identified in supraglottic LSCC. Supraglottic LSCC is a genetically complex tumor type and aCGH was demonstrated to be effective in the determination of molecular profiles with higher resolution. The present results enable the identification of putative target oncogenes and tumor suppressor gene mapping in supraglottic LSCC.