Upfront neck dissection versus concurrent chemoradiotherapy in stage T1–3N3 hypopharyngeal carcinoma: A comparative study of clinical outcomes and predictive factors

doi:10.21203/rs.3.rs-2882341/v1

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Upfront neck dissection versus concurrent chemoradiotherapy in stage T1–3N3 hypopharyngeal carcinoma: A comparative study of clinical outcomes and predictive factors

https://doi.org/10.21203/rs.3.rs-2882341/v1

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Purpose

This study assessed the efficacy of upfront neck dissection (ND) versus concurrent chemoradiotherapy (CRT) in patients diagnosed with T1–3N3 hypopharyngeal carcinoma (HPC).

Methods

This retrospective study enrolled patients with T1–3N3 HPC who had undergone upfront ND followed by CRT (upfront group) or only CRT (CRT group). Local control rate, neck control rate, metastasis-free rate, disease-free survival, disease-specific survival, and overall survival were compared between the upfront and CRT groups. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify the survival-related clinical and systemic factors.

Results

Forty-eight patients were enrolled in this study, with 18 in upfront group and 30 in CRT group. The groups differed significantly in terms of neck control rate (p = 0.000121) and disease-free survival (p = 0.0256). The upfront CRT group showed a significantly better overall survival (OS) than that of the unresectable CRT group (p = 0.046). Among the various factors, node status, body mass index, and platelet-to-lymphocyte ratio were significantly associated with OS in a univariate analysis.

Conclusion

Upfront ND can be recommended for T1–3N3 HPC, provided resectability is feasible.

hypopharyngeal carcinoma

upfront neck dissection

chemoradiotherapy

N3 lymph node

Hypopharyngeal carcinoma (HPC) is a rare type of cancer that accounts for approximately 3–5% of all head and neck squamous cell carcinomas (HNSCC) [1]. The prognosis for HPC is poor, with a 5-year survival rate of approximately 40% [2], making it one of the most fatal head and neck cancers [3, 4]. Moreover, most patients are diagnosed at an advanced stage, leading to unfavorable outcomes [5]. Radical surgery for advanced HNSCC is associated with voice loss and deterioration in quality of life. Therefore, chemoradiotherapy (CRT) is generally performed to preserve the laryngeal function [6, 7]. However, the recurrence rate after radiotherapy for HPC remains significantly high at 40–60% for advanced tumors [8], and treatment outcomes need to be improved. Distant metastases and locoregional failure remain critical treatment challenges [9]. To address these challenges, various approaches to improve the outcome of treating HPC have been explored [5, 7, 10–12]. A key factor in this is an improved control of the cervical lymph nodes.

Metastatic lymph nodes are less sensitive to CRT than primary tumors [13, 14]. Therefore, the clinical outcomes and overall prognosis of N3 cases with extranodal extension are poor [15]. One approach for improving cervical lymph node control rates is upfront neck dissection (ND) before CRT [5, 16, 17]. However, evidence regarding its impact on prognosis is conflicting, with some studies showing improved outcomes [17, 18] and others suggesting no significant improvements [9, 19]. The retrospective nature of these studies limits the generalizability of their conclusions to different patient backgrounds. If the primary tumor and stage are carefully selected, this therapeutic approach may yield greater efficacy [20]. In other words, upfront ND may be a good treatment for N3 patients with early primary lesions, who can be treated adequately using CRT.

In this study, we assessed the efficacy of upfront ND versus concurrent CRT in patients diagnosed with stage N3 HPC, which is recognized as a particularly adverse prognostic factor in head and neck malignancies. Additionally, we also investigated the clinical and systemic factors associated with prognosis of N3 HPC.

Patient and data collection

We enrolled patients with N3 and T1–3 squamous cell carcinoma of the hypopharynx. They underwent upfront ND followed by CRT or radiotherapy (RT) (upfront group) or received only CRT or RT (CRT group) at Tokai University Hospital, Kanagawa, Japan from January 2010 to June 2022. Disease staging was performed according to the eighth edition of the American Joint Committee of Cancer/Union for International Cancer Control TNM classification criteria. Before treatment, all patients underwent blood tests, endoscopy, computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT. Patients with a history of radiotherapy in the head and neck, prior head and neck surgery, non-squamous cell carcinoma, distant metastases, or a performance status (PS) of 3 or higher were excluded. Unresectable lymph nodes were defined as invasion of the carotid artery or extensive deep cervical muscle. In principle, upfront ND is recommended for resectable lymph nodes; however, definitive (C) RT is performed in patients refusing the surgery. Patients with unresectable lymph nodes were treated with definitive (C) RT.

The Institutional Review Board of the Tokai University Hospital (22R233) approved this study, which was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was not required because this study was a retrospective analysis of existing administrative and clinical data.

Treatment

Neck dissection

The extent of ND was designated as levels II–V. The sternocleidomastoid muscle, accessory nerves, internal jugular vein, and deep cervical muscles were resected based on the lymph node invasion. All ND procedures were performed before definitive (C) RT (upfront ND).

Chemoradiotherapy

Patients underwent three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. The prescribed total dose was 66–70 Gy, delivered in 33–35 fractions. Patients who underwent upfront ND commenced radiotherapy within 2 months of the surgery. The concurrent chemotherapy regimen consisted of cisplatin (CDDP) (100 mg/m² every 3 weeks), carboplatin (CBDCA) (area under the concentration-time curve (AUC) 5), cetuximab (400 mg/m² and 250 mg/m² weekly), or CDDP (70 mg/m² every 4 weeks) combined with 5-fluorouracil (700 mg/m² over 24 h on days 1–4, every 4 weeks). The aforementioned chemotherapy regimen was the most commonly used during the study period. Follow-up evaluations were conducted once a month during the first year, every 2 months during the first 2 years, every 3 months during the third year, and every 6 months until the fifth year. Radiological examination, including CT, MRI, and PET/CT, was performed every 3–6 months.

Endpoints and variables

The patients were divided into upfront and CRT groups based on their treatment. Treatment-related factors, including age, sex, T classification, primary site, radiotherapy (RT or CRT), radiation dose, and concurrent chemotherapy regimens, were analyzed.

Local control rate (LCR) or neck control rate (NCR) was defined as the time from the start of the treatment to the date of local or neck relapse. The distant metastasis-free rate (MFR) was defined as the time from the start of the treatment to the date of distant metastasis. Disease-free survival (DFS) was defined as the time from the beginning of the treatment to the cutoff date when disease progression or death, for any reason, was no longer observed. Disease-specific survival (DSS) was defined as the time from the beginning of the treatment to the date of death or the cutoff date for a specific cause. Overall survival (OS) was defined as the time from the start of the treatment to the date of death, regardless of the cause or cutoff value.

We classified clinical factors into two categories based on age (< 70 vs. ≥70 years), sex (male vs. female), tumor size (T1 & T2 vs. T3), tumor location (pyriform sinus vs. post cricoid & posterior wall), radiotherapy method (RT vs. CRT), total radiation dose (≤ 66 Gy vs. >66 Gy), chemotherapy type (CDDP vs. other agents), treatment approach (upfront vs. CRT), and lymph node status (resectable vs. unresectable). Additionally, as a systemic factors, we evaluated body mass index (BMI), albumin (Alb), C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR) [21], neutrophil-to-lymphocyte ratio (NLR) [22], lymphocyte-to-monocyte ratio (LMR) [23], systemic immune-inflammation index (SII) [24], controlling nutritional status (CONUT) [25], prognostic nutritional index (PNI) [26], prognostic index (PI) [27], systemic inflammation response index [28], and Glasgow Prognostic Score (GPS) [29] using pre-treatment blood tests and investigated their association with prognosis. Based on the blood test results, the vvalues of systemic factors were as follows: PLR, the ratio of platelet count to lymphocyte count; NLR, the ratio of neutrophil count to lymphocyte count; LMR, the ratio of lymphocyte count to monocyte count; SII, which is neutrophil count × platelet count/ total lymphocyte count; CAR, the ratio of serum CRP level to serum Alb level; CONUT score, calculated using the serum Alb level, total lymphocyte count, and total cholesterol level; PNI, 10 × serum Alb level + 0.005 × total lymphocyte count; PI, measured using the serum CRP level and leucocyte count. A CRP level > 1 mg/dL was given a score of 1, whereas a CRP level ≤ 1 mg/dL was defined as a score of 0. GPS was measured using the serum CRP and Alb levels. A CRP level > 1.0 mg/dL and Alb level < 3.5 g/dL were given a score of 2, while a CRP level > 1.0 mg/dL or Alb level < 3.5 g/dL was given a score of 1. A CRP level ≤ 1.0 mg/dL and Alb level ≥ 3.5 g/dL were given a score of 0.

Post-treatment conditions

Post-treatment sequelae, including chylous fistulas, aspiration pneumonia, tube feeding, and tracheostomy, were examined in both the upfront and CRT groups. Dysphagia was assessed using the Functional Outcome Swallowing Scale (FOSS), 6 months after the surgery, to evaluate swallowing function.

Statistical analysis

LCR, NCR, MFR, DFS, DSS, and OS were estimated using the Kaplan-Meier method and evaluated using the log-rank test between the upfront and CRT groups. OS based on T classification was estimated using the Kaplan-Meier method. The effect of T classification on survival was evaluated using a log-rank test. Furthermore, to investigate the impact of differences in lymph node status and in treatment methods on prognosis, we divided the patients into the following three groups: upfront (Upfront), CRT with resectable lymph node (CRT-R), and CRT with unresectable lymph node (CRT-UR). Survival rates were estimated using the Kaplan-Meier method, and a log-rank test was conducted to examine significant differences. Pearson’s chi-square test or Fisher’s exact test was used to analyze categorical variables. The Bonferroni correction was applied for multiple comparisons. Continuous data were compared using the Mann-Whitney U test.

Univariate and multivariate analyses using Cox proportional hazards models were performed to identify the clinical and systemic factors associated with OS. A multivariate analysis was performed after adjusting for age. The cutoff values for systemic factors were determined by referring to the receiver operatorating characteristic curves. Cox regression model analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Japan). All other statistical analyses were performed using GraphPad Prism 8 software (GraphPad Software Inc., San Diego, CA, USA). Statistical significance was defined as p < 0.05.

Patient characteristics

Forty-eight patients were enrolled in this retrospective analysis, with 18 in upfront group and 30 in CRT group. The median age of patients in the upfront group was 70.5 years (range, 59–94), whereas that of patients in the CRT group was 66.5 years (range, 48–86). The difference in the median age between the two groups was statistically significant (p = 0.031). There were 46 men (96%) and two women (4%) in the entire cohort. In the T classification, eight (17%), 25 (52%), and 15 (31%) patients had T1, T2, and T3 tumors, respectively. The distribution of the T classifications was not significantly different between the groups (p = 0.141). Among the primary sites, 35 (73%), five (10%), and eight (17%) patients had tumors in the pyriform sinus, posterior wall, and post-cricoid region, respectively. Out of the 48 patients, six (13%) received RT and 42 (87%) received CRT. The median total dose of RT was 66 Gy (range, 60–70 Gy), with no significant difference in the median total dose of RT between the groups (p = 0.428). The chemotherapy regimen comprised CDDP in 19 (40%) patients, CBDCA in six (13%) patients, CDDP + 5-fluorouracil in 15 (31%) patients, and cetuximab in two (4%) patients.

Kaplan–Meier curves of LCR (a), NCR (b), MFR (c), DFS (d), DSS (e), and OS (f) in the upfront and CRT groups are illustrated in Fig. 1.

There was a significant difference in neck control rate between the upfront and CRT groups (p = 0.000121) (Fig. 1b). The 5-year NCR was 92.3% in the upfront group and 31.6% in the CRT groups. Furthermore, there was a significant difference in DFS between the groups (p = 0.0256), with the median (95% confidence interval) disease-free survival rate being 15 months (6-NA) for the upfront group and 7 months (5–12) for the CRT group (Fig. 1d).

The LCR, MFR, DSS, and OS did not differ significantly between the upfront and CRT groups (p > 0.05). However, there was a significant trend towards better survival in the upfront treatment group in terms of the DSS and OS (p < 0.1) (Figs. 1e and 1f). In contrast, the MFR results showed that the survival rate of the CRT group was significantly higher than that of the control group (Fig. 1c).

Figure 2 shows the Kaplan–Meier curves of OS according to the T stage (Fig. 2a) and treatment (Fig. 2b). Based on the T classification, patients with T1 tumors had a median OS of 27 months, whereas those with T2 and T3 tumors each had a median OS of 23 months. The 3-year OS rates were 46.9%, 43.1%, and 28.6%, respectively. However, patients with T1, T2, and T3 tumors did not differ signififcantly by log-rank test (p = 0.755).

Regarding the lymph node status, the Kaplan-Meier curve for treatment showed significant differences among the three groups (p = 0.0312). Moreover, the upfront treatment group showed significantly better OS than that in the CRT-UR group (p = 0.046). The 3-year and 5-year OS rates were 56.7%, 35.7%, and 12.5% for upfront ND, CRT-R, and CRT-UR, respectively.

Table 2 presents the results of univariate and multivariate analyses of the clinical factors associated with OS. A univariate analysis revealed that node status (resectable vs. unresectable), BMI (PLR), and albumin levels were significantly associated with OS. In the multivariate analysis, node status and PLR were significant prognostic factors for OS.

Univariate and multivariate analyses were conducted to identify the clinical and systemic factors that significantly impacted OS (Table 2). Among the clinical factors, node status was a significant prognostic factor in both analyses. Patients with resectable lymph nodes had a significantly better OS. No other clinical factors had a significant OS in either univariate or multivariate analyses. Among the systemic factors, BMI, PLR, and treatment were significantly associated with OS in the univariate analysis. In the multivariate analysis, BMI and PLR remained significant prognostic indicators.

Table 3 summarizes the posttreatment conditions of the study population. A chylous fistula was observed in one patient (5.6%) in the upfront ND group, whereas aspiration pneumonia was observed in seven patients (14.6%), of which two (11.1%) were in the upfront ND group and five (16.7%) in the CRT group.

Two (4.2%) patients received tube feeding in the CRT group. Furthermore, only one (2.1%) patient in the CRT group required a tracheostomy. Evaluation of the swallowing function using FOSS showed no significant difference between the upfront and CRT groups (median FOSS scores:1 vs 1.23, respectively; p = 0.1087).

In the treatment of head and neck cancers, metastatic lymph node management has a significant impact on the prognosis, and improving the control rate is an important challenge. In particular, patients with N3 lymph node metastasis have a poor prognosis. Induction chemotherapy [10, 30] and upfront ND [5, 16–18] have been reported as useful therapeutic strategies in patients with N3 lymph nodes. Therefore, we retrospectively investigated the effectiveness of upfront ND in hypopharyngeal cancer patients.

In this study, we examined LCR, NCR, MFR, DFS, DSS, and OS in both the upfront ND and CRT groups. We observed a statistically significant outcome in the upfront ND group in terms of NCR and DFS. Furthermore, the upfront ND group showed a significant trend towards better DSS and OS outcomes. Carsuzaa et al. [19] reported that upfront ND significantly improved locoregional control and Boros et al. [17] reported that upfront ND could be associated with improved outcomes in non-oropharyngeal N3 HNSCC. In this study, DFS in the CRT group was slightly worse than that reported [12, 17], and the results declined rapidly over two years. It is possible that our study only included N3 hypopharyngeal carcinoma, especially the large amount of unresectable N3.

Based on the present findings, we conclude that UFND significantly improves the cervical control rate and contributes to OS. Furthermore, there was no difference in LCR between the two groups. These results are reasonable because the treatment for the primary lesion was the same in both groups. Additionally, regarding MFR, the CRT group showed a significant trend towards better outcomes. Another possible reason could be the presence or absence of chemotherapy. A systematic review by Elicin et al. [31] reported a statistically significant decrease in oncological outcomes in the group receiving (C) RT alone. In this study, 77.8% of the patients in the upfront group received postoperative radiotherapy with chemotherapy, whereas 93.3% of the patients in the CRT group received chemotherapy, which was not significant but more common in the CRT group. It was also considered that a maximum of 2-month delay in starting chemotherapy in the upfront group influenced the results.

Additionally, we conducted a detailed study of T classification and lymph node status. Regarding the T classification and OS rate, the results showed that as the T stage increased, the 5-year survival rate decreased. However, no significant differences were observed in log-rank tests. Resultantly, the T stage was not strongly associated with prognosis in N3 cases. Petersen et al. [4] investigated the survival rates of patients with hypopharyngeal cancer according to various T classifications. Their results indicated that CRT and total laryngectomy were associated with similar outcomes up to T3, whereas TL was recommended for T4 stages. Our results also showed no significant differences among the T stages. Our analysis suggests that CRT is an appropriate treatment option for local control up to stage T3 to preserve laryngeal function.

Moreover, we conducted an analysis based on the lymph node resectability criteria. Both resectable and unresectable lesions were present in N3 tumors. All patients in the upfront treatment group had resectable lesions, whereas both resectable and unresectable lesions were observed in the CRT group. Consequently, for subsequent analyses, the CRT group was further subdivided based on the resectability. The results revealed that the 5-year survival rate of the upfront group was 56.7%, while that of the CRT-UR group was 12.5%, indicating that the upfront group showed significantly better results in the log-rank test. Furthermore, it became apparent that the survival rate in the CRT-R group was 35.7%, which was higher than that in the CRT-UR group (12.5%). These findings suggest that resection may serve as a fundamental approach for improving the prognosis of resectable N3 lymph nodes. However, different treatment strategies must be incorporated in unresectable cases. Du et al. [10] reported that induction chemotherapy (ICT) is useful in N3 HNSCC and should be considered as a treatment option. Further studies on ICT are required in patients with unresectable N3 cancers.

Univariate and multivariate analyses were performed to identify clinical and systemic factors associated with OS. Clinical factors such as lymph node status (resectable or unresectable) and systemic factors such as BMI and PLR were significantly associated with OS in both univariate and multivariate analyses. Consistent with the results, unresectable lymph nodes have been demonstrated to significantly affect the prognosis of HPC. Chen et al. [32] reported that a low BMI was associated with severe postoperative complications and poor prognosis in gastric cancer, suggesting that BMI may similarly affect prognosis in hypopharyngeal cancer. Takenaka et al. [33] reported that PLR was associated with poor survival in patients with HNSCC. Additionally, PLR is reportedly associated with poor prognosis in various carcinomas [34–36]. These results showed that PLR was also a prognostic factor for HPC. BMI and PLR are easily measurable factors. Therefore, these systemic factors should be considered when deciding future treatment plans.

This retrospective study had several limitations. First, this was a single-center retrospective study that evaluated a small number of patients. Second, systemic factors must be interpreted cautiously, owing to the numerous factors involved. Finally, a multicenter collaborative study with larger patient cohorts is needed to optimize upfront ND following CRT for HPC.

Our retrospective study highlights the efficacy of upfront ND in HPC at the T1–3N3 stage. Upfront ND is a more effective treatment option than CRT for improving NCR and DFS. The OS in the CRT-UR group was lower than that in the CRT-R group. Among various factors, node status, BMI, and PLR were significantly associated with OS. Our results demonstrate that upfront ND can be recommended for T1–3N3 HPC, providing resectability.

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

Funding: None

Competing interests: None

Ethics approval: The institutional review board of the Tokai University Hospital approved the study protocol (22R233).

Consent: The institutional review board waived the informed consent requirement owing to the study’s retrospective nature.

Data availability statement: All relevant data has been presented in this manuscript

Authors’ contribution statement

Conceptualization, A.S and T.F.; methodology, A.S. and T.F.; validation, A.S., H.I. and K.O.; formal analysis, A.S.; investigation, A.S.; resources, A.S., K.E, M.Y, T.T., A.Y., T.W., T.I., D.M. and K.O.; data curation, A.S.; writing—original draft preparation, A.S.; writing—review and editing, A.S.; visualization, A.S.; supervision, K.O.; project administration, A.S. All authors have read and agreed to the published version of the manuscript.

Galeano Machuca MP, Ng DL, Terng SD, Wu WC, Cheng CT (2021) Survival and complications with a surgical approach in advanced hypopharyngeal cancer. J Surg Oncol 123:1540–1546. https://doi.org/10.1002/jso.26440
Newman JR, Connolly TM, Illing EA, Kilgore ML, Locher JL, Carroll WR (2015) Survival trends in hypopharyngeal cancer: a population-based review. Laryngoscope 125:624–629. doi: 10.1002/lary.24915. Epub 2014 Sep 15. PMID: 25220657
Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP (2005) Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 114:806–816. 10.1002/ijc.20740. PMID: 15609302
Petersen JF, Timmermans AJ, van Dijk BAC, Overbeek LIH, Smit LA, Hilgers FJM et al (2018) Trends in treatment, incidence, and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands. Eur Arch Otorhinolaryngol 275:181–189. 10.1007/s00405-017-4766-6
Al-Mamgani A, Meeuwis CA, van Rooij PH, Mehilal R, Basdew H, Sewnaik A, Levendag PC (2013) Node-positive hypopharyngeal cancer treated by (chemo)radiotherapy: impact of up-front neck dissection on outcome, toxicity, and quality of life. Head Neck 35:1278–1286. 10.1002/hed.23109Epub 2012 Aug 21. PMID: 22907928
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098. 10.1056/NEJMoa031317. PMID: 14645636
Paximadis P, Yoo G, Lin HS, Jacobs J, Sukari A, Dyson G, Christensen M, Kim H (2012) Concurrent chemoradiotherapy improves survival in patients with hypopharyngeal cancer. Int J Radiat Oncol Biol Phys 82:1515–1521. 10.1016/j.ijrobp.2011.04.064Epub 2011 Jun 12. PMID: 21658855; PMCID: PMC3870198
Akbaba S, Held T, Lang K, Hoerner-Rieber J, Zaoui K, Forster T et al (2019) Salvage radiotherapy for recurrent hypopharyngeal and laryngeal squamous cell carcinoma (SCC) after first-line treatment with surgery alone: a 10-year single-centre experience. Radiat Oncol 14:34. 10.1186/s13014-019-1238-8PMID: 30782197; PMCID: PMC6381740
Chen WY, Chen TC, Lai SF, Liang TH, Huang BS, Wang CW (2019) Outcome of bimodality definitive chemoradiation does not differ from that of trimodality upfront neck dissection followed by adjuvant treatment for > 6 cm lymph node (N3) head and neck cancer. PLoS ONE 14:e0225962. 10.1371/journal.pone.0225962PMID: 31794576; PMCID: PMC6890260
Du C, Blanchard P, Even C, Boros A, Gorphe P, Breuskin I et al (2020) Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma. Head Neck 42:426–433. 10.1002/hed.26021Epub 2019 Dec 4. PMID: 31800157
Liu XK, Li Q, Zhang Q, Su Y, Shi YX, Li H et al (2012) Planned neck dissection before combined chemoradiation in organ preservation protocol for N2-N3 of supraglottic or hypopharyngeal carcinoma. ORL J Otorhinolaryngol Relat Spec 74:64–69 Epub 2012 Feb 9. PMID: 22327028
Sato MP, Otsuki N, Kitano M, Ishikawa K, Tanaka K, Kimura T et al (2021) Up-front neck dissection followed by chemoradiotherapy for T1-T3 hypopharyngeal cancer with advanced nodal involvement. Head Neck 43:3810–3819. 10.1002/hed.26881Epub 2021 Sep 22. PMID: 34549854; PMCID: PMC9292839
Prades JM, Timoshenko AP, Schmitt TH, Delolme MP, Francoz M, Martin C et al (2008) Planned neck dissection before combined chemoradiation for pyriform sinus carcinoma. Acta Otolaryngol 128:324–328. doi: 10.1080/00016480701477669. PMID: 17851948
Strasser MD, Gleich LL, Miller MA, Saavedra HI, Gluckman JL (1999) Management implications of evaluating the N2 and N3 neck after organ preservation therapy. Laryngoscope 109:1776–1780. doi: 10.1097/00005537-199911000-00010. PMID: 10569406
Tao Y, Auperin A, Graff P (2017) Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials. Oral Oncol 71:61–66. https://doi.org/10.1016/j.oraloncology.2017.06.002
Elicin O, Albrecht T, Haynes AG, Bojaxhiu B, Nisa L, Caversaccio M et al (2016) Outcomes in advanced head and neck cancer treated with up-front neck dissection prior to (chemo)radiotherapy. Otolaryngol Head Neck Surg 154:300–308. 10.1177/0194599815608370
Boros A, Blanchard P, Dade A, Gorphe P, Breuskin I, Even C et al (2021) Outcomes in N3 head and neck squamous cell carcinoma and role of upfront neck dissection. Laryngoscope 131:E846–E850. 10.1002/lary.28893Epub 2020 Aug 24. PMID: 32833260
Paximadis PA, Christensen ME, Dyson G, Kamdar DP, Sukari A, Lin HS et al (2012) Up-front neck dissection followed by concurrent chemoradiation in patients with regionally advanced head and neck cancer. Head Neck 34:1798–1803. 10.1002/hed.22011Epub 2012 Feb 6. PMID: 22307819; PMCID: PMC3870203
Carsuzaa F, Dufour X, Gorphe P, Righini C, Cosmidis A, Rogé M et al (2020) Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study. Clin Otolaryngol 45:877–884. doi: 10.1111/coa.13615. PMID: 32729227
D'Cruz AK, Pantvaidya GH, Agarwal JP, Chaukar DA, Pathak KA, Deshpande MS (2006) Split therapy: planned neck dissection followed by definitive radiotherapy for a T1, T2 pharyngolaryngeal primary cancer with operable N2, N3 nodal metastases–a prospective study. J Surg Oncol 93:56–61. doi: 10.1002/jso.20399. PMID: 16353188
Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W et al (2017) Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer 111:176–181 Epub 2017 Jul 24. PMID: 28838390
Mariani P, Russo D, Maisto M, Troiano G, Caponio VCA, Annunziata M et al (2022) Pre-treatment neutrophil-to-lymphocyte ratio is an independent prognostic factor in head and neck squamous cell carcinoma: Meta-analysis and trial sequential analysis. J Oral Pathol Med 51:39–51. 10.1111/jop.13264Epub 2021 Dec 9. PMID: 34797592; PMCID: PMC9299721
Tham T, Olson C, Khaymovich J, Herman SW, Costantino PD (2018) The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 275:1663–1670. 10.1007/s00405-018-4972-xEpub 2018 Apr 13. PMID: 29651542
Wang YT, Kuo LT, Weng HH, Hsu CM, Tsai MS, Chang GH et al (2022) Systemic immun e-inflammation index as a predictor for head and neck cancer prognosis: A meta-analysis. Front Oncol 12:899518. 10.3389/fonc.2022.899518PMID: 35814369; PMCID: PMC9263088
Lin Q, Li C, Lin X, Lin S, Chen W, Chen X et al (2023) Prognostic value of controlling nutritional status score in advanced hypopharyngeal cancer. Laryngoscope. doi: 10.1002/lary.30568. Epub ahead of print. PMID: 36651579
Migita K, Matsumoto S, Wakatsuki K, Ito M, Kunishige T, Nakade H et al (2018) The prognostic significance of inflammation-based markers in patients with recurrent gastric cancer. Surg Today 48:282–291. 10.1007/s00595-017-1582-yEpub 2017 Aug 23. PMID: 28836056
Kasymjanova G, MacDonald N, Agulnik JS, Cohen V, Pepe C, Kreisman H et al (2010) The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer. Curr Oncol 17:52–58. 10.3747/co.v17i4.567PMID: 20697515; PMCID: PMC2913830
Qi Q, Zhuang L, Shen Y, Geng Y, Yu S, Chen H, Liu L et al (2016) A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer 122:2158–2167 Epub 2016 May 6. PMID: 27152949
Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ (2003) Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 89:1028–1030. 10.1038/sj.bjc.6601242PMID: 12966420; PMCID: PMC2376960
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M et al (2007) Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357:1695–1704. doi: 10.1056/NEJMoa071028. PMID: 17960012
Elicin O, Nisa L, Dal Pra A, Bojaxhiu B, Caversaccio M, Schmücking M et al (2016) Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: Rationale, complications, toxicity rates, and oncological outcomes - A systematic review. Radiother Oncol 119:185–193 Epub 2016 Mar 17. PMID: 26996775
Chen HN, Chen XZ, Zhang WH, Yang K, Chen XL, Zhang B, Chen ZX et al (2015) The impact of body mass index on the surgical outcomes of patients with gastric cancer: A 10-year, single-institution cohort study. Med (Baltim) 94:e1769. 10.1097/MD.0000000000001769PMID: 26496304; PMCID: PMC4620840
Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K et al (2018) Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta-analysis. Head Neck 40:2714–2723. 10.1002/hed.25366Epub 2018 Aug 13. PMID: 30102821
Chen N, Li W, Huang K, Yang W, Huang L, Cong T et al (2017) Increased platelet-lymphocyte ratio closely relates to inferior clinical features and worse long-term survival in both resected and metastatic colorectal cancer: an updated systematic review and meta-analysis of 24 studies. Oncotarget 8:32356–32369. 10.18632/oncotarget.16020PMID: 28404961; PMCID: PMC5458290
Lu C, Gao P, Yang Y, Chen X, Wang L, Yu D et al (2017) Prognostic evaluation of platelet to lymphocyte ratio in patients with colorectal cancer. Oncotarget 8:86287–86295. 10.18632/oncotarget.21141PMID: 29156795; PMCID: PMC5689685
Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL et al (2014) The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 31:305. 10.1007/s12032-014-0305-0Epub 2014 Oct 30. PMID: 25355641

Table 1 to 3 are available in the Supplementary Files section.

Table1.png
Table 1 Patient characteristics Abbreviations: RT, radiotherapy; CRT, Chemoradiotherapy; CDDP, Cisplatin; CBDCA, Carboplatin; 5-FU, 5-Fluorouracil. Bold indicates statistically significant p-values.
Table2.png
Table 2. Univariate and multivariate analyses of clinical and systemic factors with overall survival Abbreviations: PS, pyriform sinus; PC, post cricoid; PW, posterior wall; RT, radiotherapy; CRT, chemoradiotherapy; BMI, body mass index; Alb, albumin; CRP, C-reactive protein; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; SII, systemic immune inflammation index; CAR, CRP to Alb ratio; CONUT, controlling nutritional status; PNI, prognostic nutrition index; PI, prognostic index. Bold indicates statistically significant p-values.
Table3.png
Table 3. Post-treatment conditions Abbreviations: CRT, chemoradiotherapy; FOSS, Functional Outcome Swallowing Scale

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Upfront neck dissection versus concurrent chemoradiotherapy in stage T1–3N3 hypopharyngeal carcinoma: A comparative study of clinical outcomes and predictive factors

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Abstract

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Introduction

Material and methods

Patient and data collection

Treatment

Neck dissection

Chemoradiotherapy

Endpoints and variables

Post-treatment conditions

Statistical analysis

Results

Patient characteristics

Discussion

Conclusion

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References

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Supplementary Files

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