Donghyeok Kim and Nalee Kim contributed equally to this work.
Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT).
We retrospectively reviewed 185 candidates for LPS with cT1–2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared.
Following LPS, safe margin (≥ 5 mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2–3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not.
Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.
The incidence of hypopharyngeal cancer (HPC) is rare, less than 0.7 per 100,000 people [
Due to the anatomical vicinity, the local therapeutic extent frequently includes the uninvolved larynx [
In this context, we intended to evaluate the role of LPS, which has not previously been adequately addressed, in comparison with upfront RT. We specifically focused on the patients whose tumors could be a potential candidate for LPS, based on the initial tumor characteristics.
A full electronic search identified 262 patients who underwent curative larynx preserving treatment for biopsy-proven hypopharynx squamous cell carcinoma from 1996 till 2018 at the authors’ institute: 85 underwent upfront LPS; and 177 underwent upfront RT, respectively (
The diagnostic work-ups included physical examination, endoscopic examination of the upper aerodigestive tract (laryngopharyngoscopy and esophagoscopy), computed tomography or magnetic resonance imaging, and positron emission tomography/computed tomography (or chest computed tomography, when necessary). Any suspicious metastatic lymph node detected by physical examination and/or radiological images was evaluated by aspiration cytology (ultrasonography guided or not).
The decision on the actual treatment modality, in principle, was to be made through the multidisciplinary tumor board, with the consideration not only of tumor extent, but also of the general condition and preference of each patient. However, the decision to conduct upfront LPS was mainly determined by the surgeon’s opinion on the expectancy of adequate surgical exposure and achieving clear resection margin while preserving the functioning larynx.
Surgical approach was determined based on the primary tumor location and extent: trans-oral approach was chosen in 25 patients (42.4%); while trans-cervical pharyngotomy (open partial hypopharyngectomy) was in 34 (57.6%), respectively (
Among 59 patients in upfront LPS group, adjuvant RT with or without concurrent chemotherapy was performed in 54 (91.5%) with one or more pathologic risk factors: multiple lymph node metastases in 34 (57.6%); positive or close margin in 32 (54.2%); and extracapsular extension of involved lymph node in 28 (47.5%), respectively (
Regarding definitive RT or CCRT, the gross tumor volume of the primary tumor and lymph node metastasis was delineated based on clinical information. Next, we adopted selective neck node irradiation in clinical target volume encompassing 2.0–2.5 cm margins from grossly involved lymph node station, followed by reduced field with 1.0–1.5 cm margins to lymph node metastasis after 36 Gy, as we previously reported [
The most common systemic therapy regimen consisted of cisplatin (40 mg/m2 every 3 weeks or 40 mg/m2 weekly) delivered to 99 patients (28 in LPS+CCRT, 71 in CCRT). Cetuximab (20 mg/m2) delivered to six patients (all in the CCRT group). Other regimens were combination therapy with cisplatin. Those regimens included Taxotere combination therapy (40 mg/m2) in 16 patients (two and 14 in the adjuvant and definitive CCRT), Cetuximab in one (LPS+CCRT), 5-fluorouracil (20 mg/m2) in seven (one and six in the adjuvant and definitive CCRT), or Pembrolizumab (20 mg/m2) in one (definitive CCRT), respectively.
We collected data regarding not only the oncologic outcomes (treatment failures and survival status), but also the post-treatment complications and functional status. Severe complications were defined as any clinical situation requiring hospitalization, intensive care, intervention or surgery, and included aspiration pneumonia, dyspnea, dysphagia, and wound problems (flap failure or necrosis). Restoration of oral diet of more than blended food without assistance was defined as normal swallowing without dysphagia. Functional laryngeal preservation was defined as voluntary speech pronunciation without any assisting device. Any patients who retained tracheostomy tube were regarded as having non-functional larynx. Both voice quality and swallowing function were assessed in 12–18 months of the completion of initial treatments. The voice quality was evaluated by an auditory-perceptual evaluation method for hoarseness. In this analysis, we used the G (Grade of hoarseness) score among the GRBAS scale (Grade of hoarseness, Roughness, Breathiness, Asthenia, and Strain): 0 is normal; 1 is a slight degree; 2 is a medium degree; and 3 is a high degree, respectively [
A Wilcoxon rank sum test was used to compare continuous variables between the two groups, because the data for each variable were not normally distributed. We used Fisher’s exact test or chi-squared test to examine differences in discrete variables.
All events were measured from the date of surgery (upfront LPS group) or the first date of RT (upfront RT group) to the time of the event. The rates of overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Then, we conducted univariable and multivariable survival analyses using Cox proportional hazard models to identify potential prognostic factors. The outcomes are presented as p-values, hazard ratios (HRs) and 95% confidence intervals (CI). In the multivariable models, we included all variables with p < 0.05 in the univariable analysis. Potential multi-collinearity among variables was tested by calculating the variance inflation factor. In statistical comparisons, a p-value of less than 0.05 was considered significant. All statistical analyses were performed using IBM SPSS Statistics ver. 25 (IBM Corp., Armonk, NY) and R (ver. 3.6.3, R Foundation for Statistical Computing, Vienna, Austria).
The baseline characteristics of the patients at diagnosis are summarized in
There were 84 patients (45.4%) who developed malignancy other than HPC: 28 (47.4%) in the upfront LPS group; and 56 (44.4%) in the upfront RT group, respectively. Twenty-six patients (14.1%) were diagnosed with another malignancy within 6 months before or after diagnosis of HPC. The most common cancer types included esophageal cancer in 49 patients (26.5%), followed by other head and neck cancer in 26 (14.1%), lung cancer in 10 (5.4%), and stomach cancer in nine (4.9%), respectively. All patients with history of other malignancy was judged to tolerate the treatment plans for HPC, and treatment interruption was necessary in no patient.
With a median follow-up of 37.0 months (IQR, 11.0 to 70.0) for the entire cohort, there was no difference in follow-up period between the upfront LPS group (median, 37.0 months [IQR, 13.0 to 65.0]) and the upfront RT group (median, 35.0 months [IQR, 10.0 to 71.0]) (
Functioning larynx was more frequently preserved in the upfront LPS group (100% vs. 89.7%, p=0.010) (
Further analyses based on subgroup stratified by cT and cN status were performed (
Univariate analyses revealed that upfront LPS showed benefit over upfront RT in OS (p=0.041) and DFS (p=0.053), which, however, were not proven in multivariate analysis (HR, 0.61; 95% CI, 0.33 to 1.15; p=0.127 and HR, 0.66; 95% CI, 0.39 to 1.13; p=0.127), respectively (
In this study, we investigated the clinical outcomes following larynx-preserving approach, either upfront LPS or RT, in patients with cT1–2 HPC. Within the same cT status, the actual tumor burden could be different based on the nature of tumor growth, and well-defined tumors are easily assumed to have smaller tumor burden than diffuse and/or infiltrative ones. Even though we thoroughly re-evaluated all patients’ information with regard to cT status, there might have been a preference toward upfront LPS over upfront RT for patients with favorable performance status and localized primary tumor. Consequently, favorable outcomes following LPS could have reflected aforementioned selection bias that happened in real-world clinical practice. Subsequent subgroup analyses based on cT status also revealed that DFS advantages following upfront LPS were apparent only in cT2, but not in cT1 subsets. However, there was no significant difference between treatment groups for survival outcomes after adjusting baseline clinical characteristics.
The basic assumption of larynx preserving partial hypo-pharyngectomy seems contrary to the infiltrative and extensive mucosal/submucosal spreading nature of HPC [
Therefore, the current study addresses an important clinical issue in the management of HPC. Our first question was whether LPS is oncologically safe. Based on the currently accepted guideline, LPS seems to be suboptimal (clear resection in 37.3% of cases in our series), and frequently requires adjuvant treatments (91.5%). In cT2 tumors, LPS with adjuvant treatment seemed to offer better disease control than the upfront RT, perhaps because the addition of surgery to RT/CCRT led to a rapid decrease in the tumor burden. However, the surgical wound itself can have a negative impact on the effectiveness of RT for tumor control [
The next clinical question was the effectiveness of each treatment for the high nodal disease which is commonly seen in HPCs. Since the neck node metastases could also affect the therapeutic decision, upfront neck dissection was frequently performed in patients with bulky neck tumor (cN2–3). However, there was no apparent difference in oncologic outcomes based on subgroup analyses regarding cN status (
In real clinical practice, both performance status and clinical tumor extent are recognized as determinants of the treatment modality. In the current study, the survival outcomes did not differ significantly according to the treatment modality, with multivariable analyses. Therefore, we could postulate that the treatment modality selection based on both patient and tumor factors is appropriate in real-world practice. The treatment and prognosis for multiple primary cancers in HPC patients could also affect therapeutic decision. The oncological outcomes of patients with other primary malignancies following upfront LPS were superior to those following upfront RT (data not shown) suggesting that multiple primary cancer patients with favorable prognostic factors could have been more frequently included in the upfront LPS group.
Another factor for treatment decision is functional preservation of voice and swallowing. It is easily agreeable that the voice quality tends to be better following non-surgical therapy than following LPS. Although we did not investigate the quality of voice in detail, the ultimate rate of preserving functional larynx in the upfront RT group was inferior to that of upfront LPS group (
However, our findings are limited by the small number of patients, unnoticed selection bias, the retrospective nature of our study, and the experiences, resources, and preferences of our individual clinic. Although moderate to high alcohol consumption and presence of comorbidity were well-known unfavorable factors in the HPC patients, there was no significant correlation between outcomes and these factors in the current study [
Similar to technical advances in RT, LPS procedures are still evolving from the use of conventional magnification (microscope or endoscope) to robotics and image-guided surgery (we did not use robotics for the trans-oral approach in our series) [
We could suggest that upfront LPS with adjuvant treatment as an effective treatment option for disease control and functional preservation in selected patients. However, upfront LPS may need to be limitedly applied in consideration of tumor factor, patient performance status, and the presence of multiple primary cancers, as this approach frequently required additional adjuvant treatment. Thus, the selection of treatments for resectable HPC should be individualized based on both patient and tumor factors. This preliminary finding should be validated in a further prospective trial with large series.
Supplementary materials are available at Cancer Research and Treatment website (
The current study was approved by Institutional Review Board, and the written informed consent was waived owing to the retrospective nature. The clinical data used in the study were de-identified.
Conceived and designed the analysis: Jeong HS, Ahn YC.
Collected the data: Kim D, Kim N, Koh S, Chung MK, Son YI.
Contributed data or analysis tools: Chung MK, Son YI, Oh D, Jeong HS, Ahn YC.
Performed the analysis: Kim D, Kim N, Oh D, Jeong HS, Ahn YC.
Wrote the paper: Kim D, Kim N, Jeong HS, Ahn YC.
Yong Chan Ahn, the editor-in-chief of the
This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (no. 2018R1A2B6002920).
The funders had no further role in the study design; collection, analysis and interpretation of data; writing of the manuscript; or decision to submit this manuscript for publication.
Study scheme and subject enrollment. CCRT, concurrent chemoradiation therapy; HPC, hypopharyngeal cancer; LPS, larynx-preserving surgery; RT, radiation therapy.
Survival plots: overall survival (A) and disease-free survival (B). LPS, larynx-preserving surgery; RT, radiation therapy.
Disease-free survival plots according to T and N status: cT1 (A), cT2 (B), cN0–1 (C), and cN2–3 (D). LPS, larynx-preserving surgery; RT, radiation therapy.
Baseline characteristics of patients
Characteristic | Upfront LPS (n=59) | Upfront RT (n=126) | p-value |
---|---|---|---|
Age (yr) | 63 (58–70) | 68 (58–72) | 0.121 |
Sex | |||
Male | 58 (98.3) | 119 (94.4) | 0.439 |
Female | 1 (1.7) | 7 (5.6) | |
ECOG performance status | |||
0–1 | 55 (93.2) | 110 (87.3) | 0.340 |
2–3 | 4 (6.8) | 16 (12.7) | |
Underlying disease |
31 (52.5) | 81 (64.3) | 0.148 |
Alcohol drinking history | |||
None or weak | 37 (62.7) | 70 (55.6) | 0.289 |
Moderate | 21 (35.6) | 51 (40.5) | |
Heavy | 0 | 4 (3.2) | |
Unknown | 1 | 1 | |
Smoking history | |||
Ex-/Current smoker | 49 (83.1) | 96 (76.2) | 0.387 |
Never smoker | 10 (16.9) | 30 (23.8) | |
Double primary malignancy | |||
No | 31 (52.5) | 70 (55.6) | 0.740 |
Within 6 mo | 10 (16.9) | 16 (12.7) | |
More than 6 mo | 18 (30.5) | 40 (31.7) | |
Clinical staging | |||
cT1 | 19 (32.2) | 31 (24.6) | 0.291 |
cT2 | 40 (67.8) | 95 (75.4) | |
cN0 | 19 (32.2) | 38 (30.2) | 0.001 |
cN1 | 5 (8.5) | 36 (28.6) | |
cN2 | 26 (44.1) | 52 (41.3) | |
cN3 | 9 (15.2) | 0 | |
Pathologic staging | |||
pT1 | 18 (30.5) | ||
pT2 | 39 (66.1) | ||
pT3 | 1 (1.7) | ||
pT4 | 1 (1.7) | ||
pN0 | 18 (30.5) | ||
pN1 | 7 (11.9) | ||
pN2 | 21 (35.6) | ||
pN3 | 13 (22.0) | ||
AJCC staging | |||
I–II | 18 (30.5) | 46 (36.5) | 0.106 |
III | 7 (11.9) | 27 (21.4) | |
IV | 34 (57.6) | 53 (42.1) | |
Modality | |||
3DCRT | 16 (29.6) | 58 (46.0) | |
IMRT | 38 (70.4) | 68 (54.0) | |
Total dose (Gy) | 60.0 (59.4–66.0) | 68.4 (68.4–70.0) | |
Fractional dose, median (IQR, Gy) | 2.20 (2.00–2.20) | 2.20 (2.00–2.28) |
Values are presented as median (IQR) or number (%). 3DCRT, three-dimensional conformal RT; AJCC staging, American Joint Committee on Cancer staging manual, 8th edition; ECOG, Eastern Cooperative Oncology Group; IMRT, Intensity-modulated radiation therapy; IQR, Interquartile range; LPS, larynx-preserving surgery; RT, radiation therapy.
Details of underlying disease is summarized in
Classification according to the Federal Government Dietary Guidelines for Americans 2015–2020; None, weak=less than moderate drinking, moderate=one drink per day for women and up to two drinks per day for men, heavy=more than three drinks on any day or more than seven drinks per week for women and more than four drinks on any day or more than 14 drinks per week for men.
Overall treatment outcomes
Characteristic | Upfront LPS (n=59) | Upfront RT (n=126) | p-value |
---|---|---|---|
LPS alone (n=5), LPS+RT (n=26), LPS+CCRT (n=28) | RT alone (n=49), CCRT (n=77) | ||
37.0 (13.0–65.0) | 35.0 (10.0–71.0) | 0.637 | |
No evidence of disease | 45 (76.3) | 86 (68.3) | 0.301 |
Local recurrence/Progression | 5 (8.5) | 19 (15.1) | |
Loco-regional recurrence | 0 | 2 (1.6) | |
Regional recurrence | 4 (6.8) | 13 (10.3) | |
Regional and distant metastasis | 2 (3.4) | 2 (1.6) | |
Distant metastasis | 3 (5.1) | 4 (3.2) | |
Alive without disease | 41 (69.5) | 65 (51.6) | 0.026 |
Alive with disease | 2 (3.4) | 4 (3.2) | |
Death, cancer-specific | 9 (15.3) | 36 (28.6) | |
Death, other causes | 7 (11.9) | 21 (16.7) | |
Functioning larynx | 59 (100) | 113 (89.7) | 0.010 |
Oral feeding (more than blended diet) | 56 (94.9) | 109 (86.5) | 0.126 |
Voice quality score | 0.565±0.080 | 0.564±0.063 | 0.987 |
Swallowing score | 1.565±0.080 | 1.609±0.070 | 0.683 |
6 (10.2) | 11 (8.7) | 0.788 | |
Aspiration pneumonia | 1 | 0 | |
Flap failure | 2 | 0 | |
Dyspnea | 1 | 3 | |
Dysphagia | 1 | 2 | |
Wound infection/Radionecrosis | 1 | 6 |
Values are presented as median (IQR), number (%), or mean±SE. CCRT, concurrent chemoradiation; IQR, interquartile range; LPS, larynx-preserving surgery; RT, radiation treatment; SE, standard error.
Subgroup analysis stratified by clinical T and N status
cT1 (n=50) | cT2 (n=135) | cN0–1 (n=101) | cN2–3 (n=84) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
| |||||||||
Upfront LPS (n=19) | Upfront RT (n=31) | p-value | Upfront LPS (n=40) | Upfront RT (n=95) | p-value | Upfront LPS (n=27) | Upfront RT (n=74) | p-value | Upfront LPS (n=32) | Upfront RT (n=52) | p-value | |
| ||||||||||||
LPS alone | 4 (21.1) | - | 1 (2.5) | - | 4 (14.8) | - | 1 (3.1) | - | ||||
| ||||||||||||
LPS+RT | 8 (42.1) | - | 18 (45.0) | - | 18 (66.7) | - | 8 (25.0) | - | ||||
| ||||||||||||
LPS+CCRT | 7 (36.8) | - | 21 (52.5) | - | 5 (18.5) | - | 23 (71.9) | - | ||||
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RT alone | - | 15 (48.4) | - | 34 (35.8) | - | 45 (60.8) | - | 4 (7.7) | ||||
| ||||||||||||
CCRT | - | 16 (51.6) | - | 61 (64.2) | - | 29 (39.2) | - | 48 (92.3) | ||||
| ||||||||||||
13 (68.4) | 34 (85.0) | 15 (63.0) | 32 (100) | |||||||||
| ||||||||||||
| ||||||||||||
No evidence of disease | 14 (73.7) | 27 (87.1) | 0.273 | 31 (77.5) | 59 (62.1) | 0.110 | 20 (74.1) | 53 (71.6) | > 0.99 | 25 (78.1) | 33 (63.5) | 0.225 |
| ||||||||||||
Local recurrence/Progression | 2 (10.5) | 2 (6.5) | 3 (7.5) | 17 (17.9) | 3 (11.1) | 16 (21.6) | 2 (6.3) | 6 (11.5) | ||||
| ||||||||||||
Loco-regional recurrence | 0 | 0 | 0 | 2 (2.1) | 0 | 1 (1.4) | 0 | 1 (1.9) | ||||
| ||||||||||||
Regional recurrence | 2 (10.5) | 2 (6.5) | 2 (5.0) | 11 (11.6) | 3 (11.1) | 2 (2.7) | 1 (3.1) | 8 (15.4) | ||||
| ||||||||||||
Regional-distant metastasis | 0 | 0 | 2 (5.0) | 2 (2.1) | 1 (3.7) | 1 (1.4) | 1 (3.1) | 1 (1.9) | ||||
| ||||||||||||
Distant metastasis | 1 (5.3) | 0 | 2 (5.0) | 4 (4.2) | 0 | 1 (1.4) | 3 (9.4) | 3 (5.8) | ||||
| ||||||||||||
| ||||||||||||
Disease-free survival (%) | 63.80 | 68.10 | 0.818 | 57.00 | 36.40 | 0.023 | 56.00 | 43.30 | 0.193 | 63.20 | 45.90 | 0.095 |
| ||||||||||||
Overall survival (%) | 83.60 | 74.50 | 0.479 | 64.80 | 53.40 | 0.145 | 70.30 | 59.40 | 0.163 | 75.50 | 58.20 | 0.159 |
Values are presented as number (%) unless otherwise indicated. CCRT, concurrent chemoradiation therapy; LPS, larynx-preserving surgery; RT, radiation therapy.
Prognostic factors for overall survival and disease-free survival
No. | Overall survival | Disease-free survival | |||||||||||
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Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | ||||||||||
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HR | 95% CI | p-value | HR | 95% CI | p-value | HR | 95% CI | p-value | HR | 95% CI | p-value | ||
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Upfront RT | 126 | Reference | Reference | Reference | Reference | ||||||||
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Upfront LPS | 59 | 0.552 | 0.313–0.975 | 0.041 | 0.614 | 0.327–1.150 | 0.127 | 0.628 | 0.385–1.026 | 0.053 | 0.661 | 0.389–1.125 | 0.127 |
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1.034 | 1.008–1.061 | 0.010 | 1.018 | 0.990–1.046 | 0.208 | 1.014 | 0.991–1.037 | 0.245 | |||||
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Male | 177 | Reference | Reference | ||||||||||
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Female | 8 | 0.484 | 0.117–2.006 | 0.317 | - | - | - | 0.556 | 0.170–1.812 | 0.330 | - | - | - |
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0–1 | 165 | Reference | Reference | Reference | Reference | ||||||||
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2–3 | 20 | 4.107 | 2.252–7.492 | < 0.001 | 2.886 | 1.465–5.683 | 0.002 | 2.508 | 1.405–4.476 | 0.002 | 2.068 | 1.125–3.802 | 0.019 |
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0–1 | 103 | Reference | Reference | ||||||||||
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≥ 2 | 82 | 1.349 | 0.843–2.161 | 0.212 | - | - | - | 1.130 | 0.716–1.736 | 0.575 | - | - | - |
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None/Weak | 107 | Reference | Reference | ||||||||||
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Moderate/Heavy | 78 | 1.269 | 0.794–2.029 | 0.323 | - | - | - | 1.074 | 0.700–1.647 | 0.741 | - | - | - |
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Ex-/Current | 145 | Reference | Reference | ||||||||||
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Never | 40 | 1.689 | 0.917–3.113 | 0.093 | - | - | - | 1.591 | 0.971–2.760 | 0.099 | - | - | - |
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cT1 | 50 | Reference | Reference | Reference | Reference | ||||||||
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cT2 | 135 | 1.910 | 1.102–3.308 | 0.021 | 1.591 | 0.874–2.899 | 0.129 | 1.850 | 1.121–3.054 | 0.016 | 1.584 | 0.913–2.748 | 0.102 |
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cN0–1 | 98 | Reference | Reference | ||||||||||
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cN2–3 | 87 | 1.144 | 0.717–1.826 | 0.572 | - | - | - | 1.075 | 0.852–1.356 | 0.542 | - | - | - |
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I–II | 64 | Reference | Reference | ||||||||||
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III | 34 | 1.049 | 0.592–2.081 | 0.892 | - | - | - | 0.992 | 0.537–1.833 | 0.979 | - | - | - |
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IV | 87 | 1.283 | 0.771–2.135 | 0.338 | - | - | - | 1.183 | 0.746–1.876 | 0.476 | - | - | - |
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No | 101 | Reference | Reference | Reference | |||||||||
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Within 6 mo | 26 | 2.222 | 1.196–4.129 | 0.012 | 3.484 | 1.776–6.836 | < 0.001 | 1.433 | 0.806–2.546 | 0.220 | - | - | - |
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Others | 58 | 1.037 | 0.613–1.755 | 0.891 | 1.059 | 0.616–1.820 | 0.836 | 0.890 | 0.552–1.435 | 0.634 | - | - | - |
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3DCRT | 74 | Reference | Reference | Reference | Reference | ||||||||
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IMRT | 106 | 0.616 | 0.366–0.988 | 0.149 | 0.871 | 0.423–1.794 | 0.708 | 0.507 | 0.322–0.798 | 0.003 | 0.625 | 0.341–1.145 | 0.128 |
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~2007 | 135 | Reference | Reference | Reference | Reference | ||||||||
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2008~ | 50 | 0.579 | 0.358–0.934 | 0.025 | 0.595 | 0.290–1.217 | 0.155 | 0.631 | 0.407–0.980 | 0.040 | 0.904 | 0.502–1.629 | 0.738 |
3DCRT, three-dimensional conformal RT; AJCC, American Joint Committee on Cancer; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazards ratio; IMRT, intensity-modulated radiation therapy; LPS, larynx-preserving surgery; RT, radiation therapy.