Survival of T4aN0 and T3N + laryngeal cancer patients: a retrospective institutional study and systematic review




Abstract


Objective


We aim to assess the correlation of tumor and nodal staging to survival in pT3N + and T4aN0 laryngeal cancer with subgroup analysis within stage IVa (pT4N0 and pT3N2).


Study design


Retrospective cohort study with systematic review of the literature.


Setting


Hotel Dieu de France University Hospital (tertiary referral center).


Subjects and methods


Laryngeal cancer patients’ registries were reviewed from 1998 to 2012 selecting pT3N + and pT4aN0 patients treated by primary total layngectomy. Overall survivals were compared using Log rank and Kaplan–Meier analysis. A systematic review was performed by 2 reviewers including all the articles reporting the outcome of these categories of patients. Online databases, including PubMed and EMBASE, were used. Reference sections of identified studies were examined for additional articles.


Results


Thirteen T3N + patients and 19 T4aN0 patients treated by primary total laryngectomy were included. Five-year overall survival for T3N +, T3N2 and T4aN0 was respectively 33%, 32.1% and 73.7%. Due to the small sample, the difference was not significant.


The systematic review revealed three articles reporting overall survival outcome for the T4N0 group and 6 articles for the T3N +. At 5 years, the survival ranged from 62.5% to 73% in T4N0 and from 32.2% to 77% in T3N +.


Conclusion


In advanced stage laryngeal cancer, T4aN0 tends toward a better survival than T3N + especially when compared to T3N2 although they are grouped in the same TNM stage IVa.



Introduction


Laryngeal cancer is among the most common cancers of the upper aerodigestive tract. Each year, approximately 10,000 persons in the United States are diagnosed with cancer of the larynx and it accounts for 2.4% of new malignancies worldwide every year . Laryngeal cancer is the 20th most common cancer in Europe, with approximately 39,900 new cases diagnosed in 2012 (1% of the total) . It is the 11th most common form of cancer in men worldwide, typically affecting middle aged men . The glottis is the most common subsite. Squamous cell carcinoma is the predominant histological type . The main risk factor is smoking, with alcohol acting as a synergistic factor .


Survival rates of laryngeal cancer patients range from 73% to 92% for early disease stage (I and II) and from 50% to 64% for advanced disease stage (III and IV) . Many prognostic factors have been studied and linked to the survival of laryngeal cancer. They include: resection margin , treatment modality , site of origin, disease stage , extracapsular spread , tumor volume , tumor grade , perineural invasion and lymphatic vessel density . Some of these factors are classified by the NCCN guidelines as adverse features associated with a worse prognosis: extracapsular nodal spread, positive margins, pT4, N2 or N3 nodal disease, perineural invasion and vascular embolism .


Advanced-stage carcinoma of the larynx corresponds to T3N0, T1-3N1 (stage III), T4aN0, T4aN1, T1-T4aN2 (stage IVa) and T4b, N3 (stage IVb) with stage IVc reserved for any metastatic disease . The independent effect of T and N stages on survival is well established but not directly compared in the literature.


In the present study, we aim to assess the correlation of tumor and nodal staging to survival outcomes in pT3N + and pT4aN0 laryngeal cancer patients treated by primary total laryngectomy and neck dissection +/− adjuvant therapy through a retrospective institutional case series and systematic review of the literature. In addition, subgroup analysis within stage IVa is made by comparing pT3N2 to pT4No. To the best of our knowledge, no systematic review on this topic was previously published in the literature.





Materials and methods



Patient selection


With the approval of the ethics committee of Hotel Dieu de France University Hospital, Beirut, Lebanon, (CEHDF 724), all cases of squamous cell carcinoma of the larynx treated in our tertiary center by total laryngectomy and neck dissection (TL) +/− Radiation/chemotherapy (R/CT) from 1998 to 2012 were reviewed. Data were collected retrospectively by reviewing patients’ registries for date of admission, age, sex, tobacco and alcohol consumption, surgery and adjuvant therapy, pathology reports and survival status.


Patients with pT3N + (N1, N2 and N3) and pT4aN0 laryngeal squamous cell carcinoma treated by primary TL-R/CT were included in the study whereas patients treated with salvage laryngectomy were excluded. For stage IVa subgroup analysis, patients with pT3N2 and pT4N0 were included. The pathological tumor description and lymph node characteristics were considered for this study.



Treatment protocol


The treatment plan was discussed during our monthly tumor board meeting with reference to our institution protocol based on the current NCCN guidelines. All selected patients underwent total laryngectomy and neck dissection (unilaterally or bilaterally depending on site and extent of tumor). All patients with clinically positive cervical lymph nodes underwent a functional or radical neck dissection depending on the N stage. In patients with clinically negative neck nodes, a selective functional neck dissection was performed.


We defined the treatment as concomitant radiochemotherapy (RCT) if the 2 treatments were given concurrently. Radiation therapy (RT) was defined as radiation alone if there was no chemotherapy treatment given concurrently. RT was indicated for at least one of the following factors: pT4a, positive margins, perineural invasion, vascular embolism and N2 or N3 nodal status. Chemotherapy (CT) was added in case of positive margins or extracapsular nodal spread.



Statistical analysis


SPSS version 21 (SPSS Inc., Chicago, IL) was used for statistical analysis. Overall survival (OS) was compared via Kaplan–Meier curves, and the log-rank test was used to compare mean survival in the 2 groups (T3N + vs. T4N0). In addition, a comparison was made between the subgroup of T3N2 and the group of patients with T4N0 laryngeal carcinoma, both considered as stage IVa in the TNM classification. Drop-outs were considered as censored information and a P value of less than 0.05 was considered statistically significant.



Systematic review



Inclusion and exclusion criteria


A systematic review of the literature was done including all original studies that compared survival outcome of T4N0 and T3N + laryngeal cancer subgroups. Only studies published in English or French were included. Exclusion criteria were: other types of survival outcomes than OS (overall survival) and survival outcome for advanced stages (III/IV) without defining the TNM subgroups.



Literature search strategy


An online search in PubMed and EMBASE was started in May 2014 for all available articles published using the following combinations of terms: “Survival T3 larynx;” “Laryngeal Neoplasms” [Mesh] AND (“Survival”[Mesh] OR “Survival Analysis”[Mesh]) AND “Neoplasm Staging”[Mesh]. Two evaluators independently selected the studies based on titles, excluding those that were not related to the theme of this review. After selection, the evaluators analyzed the abstracts of the selected articles to identify those that met the inclusion criteria. The included studies were then entirely analyzed.



Data extraction and analysis


Data were extracted by one reviewer and checked by a second reviewer. We extracted the number of patients, the TNM staging, the treatment modality, and the survival outcome (OS). Relevant modifying factors that could affect the survival outcome were also noted.





Materials and methods



Patient selection


With the approval of the ethics committee of Hotel Dieu de France University Hospital, Beirut, Lebanon, (CEHDF 724), all cases of squamous cell carcinoma of the larynx treated in our tertiary center by total laryngectomy and neck dissection (TL) +/− Radiation/chemotherapy (R/CT) from 1998 to 2012 were reviewed. Data were collected retrospectively by reviewing patients’ registries for date of admission, age, sex, tobacco and alcohol consumption, surgery and adjuvant therapy, pathology reports and survival status.


Patients with pT3N + (N1, N2 and N3) and pT4aN0 laryngeal squamous cell carcinoma treated by primary TL-R/CT were included in the study whereas patients treated with salvage laryngectomy were excluded. For stage IVa subgroup analysis, patients with pT3N2 and pT4N0 were included. The pathological tumor description and lymph node characteristics were considered for this study.



Treatment protocol


The treatment plan was discussed during our monthly tumor board meeting with reference to our institution protocol based on the current NCCN guidelines. All selected patients underwent total laryngectomy and neck dissection (unilaterally or bilaterally depending on site and extent of tumor). All patients with clinically positive cervical lymph nodes underwent a functional or radical neck dissection depending on the N stage. In patients with clinically negative neck nodes, a selective functional neck dissection was performed.


We defined the treatment as concomitant radiochemotherapy (RCT) if the 2 treatments were given concurrently. Radiation therapy (RT) was defined as radiation alone if there was no chemotherapy treatment given concurrently. RT was indicated for at least one of the following factors: pT4a, positive margins, perineural invasion, vascular embolism and N2 or N3 nodal status. Chemotherapy (CT) was added in case of positive margins or extracapsular nodal spread.



Statistical analysis


SPSS version 21 (SPSS Inc., Chicago, IL) was used for statistical analysis. Overall survival (OS) was compared via Kaplan–Meier curves, and the log-rank test was used to compare mean survival in the 2 groups (T3N + vs. T4N0). In addition, a comparison was made between the subgroup of T3N2 and the group of patients with T4N0 laryngeal carcinoma, both considered as stage IVa in the TNM classification. Drop-outs were considered as censored information and a P value of less than 0.05 was considered statistically significant.



Systematic review



Inclusion and exclusion criteria


A systematic review of the literature was done including all original studies that compared survival outcome of T4N0 and T3N + laryngeal cancer subgroups. Only studies published in English or French were included. Exclusion criteria were: other types of survival outcomes than OS (overall survival) and survival outcome for advanced stages (III/IV) without defining the TNM subgroups.



Literature search strategy


An online search in PubMed and EMBASE was started in May 2014 for all available articles published using the following combinations of terms: “Survival T3 larynx;” “Laryngeal Neoplasms” [Mesh] AND (“Survival”[Mesh] OR “Survival Analysis”[Mesh]) AND “Neoplasm Staging”[Mesh]. Two evaluators independently selected the studies based on titles, excluding those that were not related to the theme of this review. After selection, the evaluators analyzed the abstracts of the selected articles to identify those that met the inclusion criteria. The included studies were then entirely analyzed.



Data extraction and analysis


Data were extracted by one reviewer and checked by a second reviewer. We extracted the number of patients, the TNM staging, the treatment modality, and the survival outcome (OS). Relevant modifying factors that could affect the survival outcome were also noted.





Results



Patients’ characteristics


A total of 119 laryngeal cancers treated by TL +/− adjuvant therapy between 1998 and 2012 were identified, including 66 patients with T3 and T4a tumors treated by primary TL-R/CT. After excluding pT3N0 and pT4aN + patients, 13 patients with a pT3N + laryngeal carcinoma and 19 with a pT4aN0 tumor were definitively included ( Fig. 1 ).




Fig. 1


Patient selection.


The mean age was 64 years with 11 female and 21 male patients. Table 1 summarizes patients’ characteristics in the 2 groups.


Aug 23, 2017 | Posted by in OTOLARYNGOLOGY | Comments Off on Survival of T4aN0 and T3N + laryngeal cancer patients: a retrospective institutional study and systematic review

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