Patterns of regional lymph node failure of locally advanced hypopharynx squamous cell carcinoma after first-line treatment with surgery and/or intensity-modulated radiotherapy

doi:10.21203/rs.2.14672/v1

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Patterns of regional lymph node failure of locally advanced hypopharynx squamous cell carcinoma after first-line treatment with surgery and/or intensity-modulated radiotherapy

https://doi.org/10.21203/rs.2.14672/v1

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Purpose : To identify the spatial patterns of regional lymph node failure of locally advanced hypopharynx squamous cell carcinoma (SCC) after first-line treatment with surgery and/or intensity-modulated radiotherapy (IMRT). Methods : We retrospectively analyzed 123 patients of the hypopharynx SCC consecutively treated with radical surgical resection and/or IMRT. Results : Median PFS were 13 months (95% CI 6.4-19.6 months), and 11 months (95% CI 9.1-12.9 months) for patients receiving surgery and IMRT, respectively. The cervical lymph node failure was accounted for 32.5% of patients, with involved ipsilateral neck level II in 22 patients (55.0%), III in 12 patients (30.0%), IV in 2 patients (5%), VIb and VII both in 6 patients (5.0%), furthermore, involved contralateral neck level II in 7 patients (17.5%), III in 3 patients (7.5%). The commonly failure levels were the II (15.2%), III (8.7%), VIb (8.7%), and VII (10.9%) for surgery. The lymph node recurrence and persistent disease at levels II (24.7%) and III (13.0%) remained the major cause of failure following curative intent of IMRT. Conclusions: Whatever the treatment modality, levels II and III were most commonly failure regions. Because of high rate of node failure of level VIb and VII for patients receiving surgery, post-operative radiation should included of these territories in locally advanced hypopharynx SCC.

Cancer Biology

Oncology

Hypopharynx squamous cell carcinoma

Surgery

Radiotherapy

Chemotherapy

Failure pattern

Squamous cell carcinoma (SCC) of the hypopharynx is relatively rare and accounts for roughly 3% to 7% of all head and neck cancers ^[1-3]. Unfortunately, locally advanced hypopharyngeal carcinoma displays the poor prognosis with reported 5-year overall survival rate (OS) of approximately 44% ^[4], 10-year OS 13.8% ^[5] despite intensification of surgery and chemoradiotherapy treatment options. One of the most important reasons is that hypopharynx SCC is lack of symptoms in the early phase of the disease, approximately 60% of diseases present at the locally advanced stage, accompanied with mucosal and submucosal spread, and cervical lymph nodal metastasis ^[6]. The second reason for poor prognosis of hypopharyngeal cancer is that there is no efficient treatment approach for locally advanced stage disease. About 50% of patients develop a loco-regional failure in less than 12 months, and most died in the first two years ^[3].

Presently, the standard treatment for locally advanced hypopharynx SCC is multimodality treatment, including induction chemotherapy, partial or total laryngopharyngectomy with lymph node dissection, and postoperative radiation or chemoradiation as dictated by pathologic risk features, such as, positive margins or extranodal extension ^[7,8]. As for advanced unresectable tumors, such as stage IVb diseases, and for patients requiring organ preservation, concurrent radiotherapy and high-dose cisplatin is recommended treatment schedule in national comprehensive cancer network (NCCN) guideline for cancer of hypopharynx ^[8].

The intensity-modulated radiotherapy (IMRT) plays an important role as an adjunct to surgery or concurrent with chemotherapy. Accurate target volume delineation is critical to achieve favourable clinical outcomes. In 2014, the panel of experts from Europe, Asia, Australia/New Zealand, and America published a set of consensus guidelines for the delineation of the neck node levels ^[9]. However, there is still no consensus on the extent to which prophylactic treatment regional nodal basin needs to be included in adjuvant or definitive IMRT era. Moreover, few large sample studies have reported the patterns of lymph node failure after first-line treatment of hypopharynx SCC.

In our previously study, we have analyzed 176 newly diagnosed hypopharyngeal cancer. Metastatic lymph nodes at each nodal level in the ipsilateral neck was reported Ia 0.6%, Ib 4.0%, IIa 67.6%, IIb 43.8%, III 45.5%, IV 13.1%, Va 5.1%, Vb 1.7%, VIa 1.7%, VIb 12.5%, and VII 15.9%, respectively. In contrast, lower lymph nodes metastasis rate was observed in the contralateral neck, with the highest 18.2% found at level IIa. Based on these results, we proposed that nodal levels IIa, III and IIb in the ipsilateral neck should be consider as high-risk regions for prophylactic irradiation. The levels IV, VIb, VII in the ipsilateral neck and level II in contralateral neck exhibit moderate-risk regions, whereas, levels I and V were considered as low-risk regions.

In present study, we reported the follow-up results of frequency and distribution of lymph node failure at each nodal level for 123 patients with locally advanced hypopharynx SCC undergoing first-line treatment with surgery and/or IMRT.

A total of 224 patients who were newly diagnosed as hypopharynx SCC at the Shandong Cancer Hospital between January 2014 and November 2018 were reviewed retrospectively using electronic medical records and image database. This study was approved by the Institutional Review Board of the Shandong Cancer Hospital. The inclusion criteria for the present study were: (1) Histologically evident SCC of the hypopharynx, (2) Clinical or pathological TNM stage II-IV_b according to AJCC ^7th TNM classification without distant metastasis, (3) The head and neck contrast-enhanced CT and/or magnetic resonance imaging can be completely reviewed by picture archiving and communication system (INFINITT Research Ltd.) to assess the initial treatment failure, (4) Patients undergoing radical surgery or IMRT.

Exclusion criteria were as follows: (1) Imaging studies unavailable for review at the time of initial treatment failure, (2) History of any prior cancer-related treatment including chemotherapy, radiotherapy, and neck dissection to the head and neck area, (3) Radiation total dose lower to 50Gy.

Fig. 1 displayed flow chart for the inclusion. At last, in total, 123 patients enrolled in this study.

Surgery treatment

Twenty patients received total pharyngolaryngectomy with unilateral neck dissection for 14 patients, bilateral neck dissection for 6 patients. Similarly, twenty patients received partial pharyngolaryngectomy with unilateral neck dissection for 15 patients, bilateral neck dissection for 5 patients. Six patients received isolated unilateral neck dissection. The type of performed neck dissection was selective dissection. Generally, neck dissection involved levels II, III, IV and V. Level I and VIb were removed in partial patients according to tumor site, T stage, and lymph node metastasis on preoperative imaging.

Radiotherapy treatment

A total 117 (95.1%) patients received IMRT during the whole treatment procedure. Of these patients, 77 received chemoradiotherapy or definitive radiotherapy alone, 40 received postoperative radiotherapy. Irradiation is applied as a step and shoot IMRT technique using 6-MV X ray in daily fractions of 1.8–2.2 Gy from Monday to Friday. For definitive radiation therapy, the gross tumor volume (GTV) encompass the primary tumor and involved nodes. The clinical target volume (CTV) contains the GTV and areas of potential microscopic spread as well as the lymph node areas for elective lymph node irradiation. The planning target volume (PTV) accounts for set-up variations by a margin of 0.3 cm. Generally, we prescribe median dose 70Gy to gross tumor, 60Gy to high-risk subclinical regions, 50Gy to low-risk subclinical regions. As for postoperative radiation therapy, high-risk regions (CTV_high) were given 60–66 Gy, and the low-risk regions (CTV_low) 50 Gy in daily fractions of 1.8–2.0 Gy. The extension of the CTVs was defining by radiation oncologists taking into account of clinical factors including TNM stage, number and distribution of positive lymph nodes, size of metastatic lymph nodes, extension of primary tumor beyond the midline, pathological resection status, and existence of extra-capsular spread of nodal disease.

Systemic therapy

Twenty-eight (22.7%) patients received concurrent chemoradiotherapy, of 25 patients received cisplatin 75mg/m² as concurrent agents, 2 received nimotuzumab and 1 received cetuximab. 54 patients (43.9%) received induction chemotherapy. The induction chemotherapy regimens were as follows: (1) cisplatin 75 mg/m² plus 5-fluorouracil (5-FU) 750-1000 mg/m²/d from days 1–4 infusion, (2) docetaxel 75 mg/m² on day 1 plus cisplatin 75 mg/m². Three patients received cisplatin 75 mg/m² plus docetaxel 75 mg/m²plus 5-FU 500mg/m²/d from days 1–4 infusion. Induction chemotherapy was administered in 1–3 cycles every 3 weeks.

Lymph nodes analysis

The location of lymph nodes metastasis was divided into several levels in the present study according to the DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines for the delineation of the neck node levels ^[9]: Ia, submental group; Ib, submandibular group; II, upper jugular group, and level II is further subdivided into level IIa and level IIb by the posterior edge of the internal jugular vein; III, middle jugular group; IV, lower jugular group; V, posterior triangle group, and level V is further subdivided into levels Va (upper posterior triangle nodes) and Vb (lower posterior triangle nodes) using the caudal edge of the cricoid cartilage as an anatomic landmark; VIa, anterior jugular nodes; VIb, prelaryngeal, pretracheal, and paratracheal nodes; VII, retropharyngeal nodes. Lymphatic metastasis intensity (LMI) was described as the ratio of the number of positive lymph nodes to the total number of lymph nodes confirmed by histology after lymph node dissection. lymphatic metastasis ratio (LMR) was defined as the ratio of the number of patients with positive lymph nodes at the respective nodal level to the whole population.

Follow-up

After completion of treatment, patients were closely followed by every 3 months for the initial 3 years, every 6 months for years 3-5. All imaging studies were reviewed by one radiation oncologist (Dongqing Wang). Local recurrence was defined as recurrence at the site of the initial primary tumor, regional failure as the development of recurrence in cervical lymph nodes, and distant failure as metastasis in an organ outside of the head and neck. The presence of failure was determined based on the results of a clinical evaluation, systemic radiographic imaging, and biopsy. Progression-free survival (PFS) was considered as the time period from treatment completion to the time point of initial treatment failure, or last follow-up, or death.

Statistical analysis

Statistical analysis was performed using the SPSS statistical software, version 20.0. Categorical variables (LMR and LMI) were summarized as the frequencies and percentages. Estimated FPS was calculated by using the Kaplan-Meier method and compared using the log-rank test.

The patient, disease, and treatment characteristics was showed in Table 1. The median age was 58 years (range, 41 to 82 years) and majority were males (95.9%). Hypopharyngeal subsite was piriform sinus in 106 cases (86.2%), posterior hypopharyngeal wall in 9 (7.3%), and retrocricoid in 8 (6.5%). According to AJCC 7^th criteria, clinical or pathological staging were 7 (5.7%) for stage Ⅱ, 25 (20.3%) for stage Ⅲ and 91 (74.0%) for stage Ⅳ. One hundred and seventeen (95.1%) patients underwent IMRT, 40 (32.5%) postoperatively and 77 (56.9%) definitively. Forty patients (32.5%) received total or partial pharyngolaryngectomy with neck dissection, 6 received isolated unilateral neck dissection. Twenty-eight (22.7%) patients received concurrent chemoradiotherapy, and 54 (43.9%) received induction chemotherapy.
Forty-six neck dissections were performed: 35 ipsi- and 11 bi-lateral, 1148 lymph nodes were analyzed. A total of 169 nodes in 40 (86.9%) patients confirmed lymphatic metastasis, the overall LMI was 14.7% (169/1148). The LMI for ipsilateral neck was 16.4% (160/976), whereas, only 5.2% (9/172) for contralateral neck. A total of 10 patients were reported LMI at respective levels: II 20.0% (14/70), III 14.9% (7/47), IV 5.9% (3/51), V 0 (0/27), VI 8.0% (2/25), and VII 0 (0/5). For 77 patients receiving non-surgery treatment, LMR at the respective nodal levels were: II 66.2%, III 48.1%, IV 13.0%, V 5.1%, VI 13.0%, and VII 15.6%.
All patients were followed up for median time 12 months (3-84 months). The median PFS rates were 13 months (95% CI 6.4–19.6 months) for surgery treatment, and 11 months (95% CI 9.1–12.9 months) for non-surgery treatment, no significant difference was observed (p=0.732) (Fig.2). For all patients, local recurrence, cervical lymph node failure, and distant metastasis accounted for 13.0%, 32.5%, and 13.8%, respectively. Of the cervical lymph node failure, 26 patients were isolated regional lymph node failure, 9 were both nodal failure and local recurrence, and 5 were both nodal failure and distant metastasis (Fig. 3). The second primary cancers were found in 19 patients (15.4%), with esophagus cancer 18 patients, and lung cancer one patient.
Of the 40 regional nodal failures, failures involved ipsilateral neck level II in 22 patients (55.0%), III in 12 patients (30.0%), IV in 2 patients (5%), VIb and VII both in 6 patients (5.0%). The nodal failures involved contralateral neck level II in 7 patients (17.5%), III in 3 patients (7.5%). Furthermore, respective one patient was found nodal failure at level Ib and Va in ipsilateral neck, and level VIb and VII in contralateral neck (Fig. 4). Fig. 5 displayed frequency and distribution of regional lymph node failure for patients undergoing surgery, and IMRT, respectively. For patients undergoing surgery, the most commonly failure levels were the II (15.2%), III (8.7%), VIb (8.7%), and VII (10.9%). In contrast, for patients undergoing IMRT, the most commonly failure levels were the II (24.7%), and III (13.0%), then followed by VIb (5.0%), VII (2.5%), and IV (2.5%).

Our results demonstrate that approximately 47.2% of the hypopharynx SCC patients were found local-regional failure and distant metastasis with median time to the initial treatment failure was 13 months (95% CI 6.4-19.6 months) for surgery, and 11 months (95% CI 9.1-12.9 months) for IMRT. The most commonly failures in hypopharynx SCC are mainly attributed to cervical lymph node failure, account for 32.5% of patients.

It is well know that hypopharynx SCC characterized by aggressive clinical behavior and high risk tendency to invade cervical lymph nodes.

The lymph node extension is an important prognostic factor, therefore, control of regional metastasis is an essential part of treatment for hypopharynx SCC. Presently, there is no agreement on the best treatment approach for hypopharyngeal SCC. Definitive chemoradiation strategy arose from the RTOG 91-11 trial ^[10,11] which demonstrated improved loco-regional control and laryngeal preservation rates has become an important approach for locally advanced hypopharyngeal SCC. By means of prophylactic neck irradiation (PNI), the incidence of nodal failure can be reduced to 4% in head and neck cancers ^[12]. Therefore, PNI is an important IMRT component in the treatment of hypopharyngeal carcinoma.

In the present study, nodal involvement mainly concerned levels II (66.2%) and III (48.1%), then followed by levels IV, VI, and VII (13.0%, 13.0%, and 15.6%, respectively), while level V showed involvement in 5.1% of patients. As comparing with ipsilateral neck, the risk of metastasis for contralateral neck tend to be lower (LMI: 16.4% vs. 5.2%). These results are in agreement with our previous study and the literature ^[13]. However, few studies have reported the outcomes of regional lymph node failure for locally advanced hypopharynx SCC after treatment with IMRT. Sommat et al. ^[14]reported a retrospective analysis of 58 patients (stage III-IVb 95%) with hypopharyngeal cancer treated with curative intent radiotherapy (RT). In Sommat’s study, 88% of patients managed to achieve complete response 3 months after completion of treatment, loco-regional recurrence remained the major cause of failure following curative intent RT. Most deaths occurred in patients who succumbed to loco-regional rather than systemic failure. However, only 50% of patients undergone IMRT in Sommat’s study, half part of patients treated using a 2-dimensional technique. Daly et al. ^[15] recruited 42 patients with newly diagnosed SCC of hypopharynx (23 patients) and larynx (19 patients) underwent IMRT, 11 postoperatively and 31 definitively at Stanford University Medical Center. Median follow-up was 30 months, 5 patients developed a loco-regional failure or had persistent disease, with a median time to failure of 12.1 months. Three local failures occurred within the high-dose region and 3 occurred in regional nodes. No marginal misses were observed. The author considered that loco-regional relapses occurred in the high-dose volumes, suggesting that target volume delineation was adequate but further dose-escalation and more aggressive treatment may be needed. Huang et al. ^[16] retrospectively reviewed 47 patients with locally advanced resectable SCC of hypopharynx underwent primary surgery or definitive IMRT with concurrent platinum-based chemotherapy (CCRT). The 5-year survival rate, disease-free survival, and loco-regional progression-free survival of surgery and CCRT group was 33% and 56%, 25% and 41%, 15% and 53%, respectively. Loco-regional progression was the main cause of failure in both groups. Eleven patients had neck failure; 8 in the ipsilateral neck, 2 in the contralateral neck, and 1 in the tracheostoma site. All were in-field failure in the PTV₂ (60Gy). One retrospective study ^[17] reported by Chun et al. included 54 patients receiving definitive radiotherapy with or without chemotherapy. Thirty patients received IMRT and 24 patients received 3D-CRT. With median follow-up time was 42.3 months, there were 20 loco-regional failures discovered. Estimated crude loco-regional recurrence free survival at 3 years were 64.1%. Of the 20 loco-regional failures, 14 were isolated local failures, 4 were isolated regional nodal failures, and 2 were both. Of the 6 regional nodal failures, failures involved ipsilateral neck level II in 3 patients, ipsilateral neck level III in 1 patient, paraesophageal lymph node in 1 patient, and bilateral neck level II in 1 patient. Among the loco-regional failures, 17 were observed in the PTV high region, while 2 were in the PTV intermediate region and 1 patient had out-of-feld failure (paraesophageal lymph node), but was also accompanied by local failure within the PTV High region. Pignon et al. ^[18] found that IMRT failure in the low-neck supraclavicular field was very uncommon.

Our center has employed IMRT for the definitive treatment of head and neck cancers nearly for 10 years. Our study results demonstrated the poor outcome expected in hypopharyngeal cancer with median PFS rates were approximately one year after first-line treatment. The regional cervical lymph node recurrence and persistent disease remained the major cause of failure following curative intent of IMRT. Approximately 70% of nodal failures were observed in the PTV high or intermediate regions. In our study, the most commonly failure levels were the II (24.7%), and III (13.0%), then followed by VIb (5.0%), VII (2.5%), and IV (2.5%). The nodal failures at level IV and VII was found only in one patients, respectively. In our study, lymph node failure was mostly involved in ipsilateral neck, only 2 patients developed isolated level II failure in contralateral neck, and one patient developed level II failure in bilateral necks. Regarding our patients received IMRT enrolled in this study, more than half of patients have severe lymph node involvement and were not suitable candidates for selective lymph node dissection. Approximately 80% of them displayed lymph node metastasis with liquefactive necrosis in lymph nodes. After completion of IMRT treatment, majority of them in our cohort presented nodal residue. Pitifully, because of extra capsular extension (for example vessels and soft tissue invasion), or nodal failures accompanied by local recurrence or distant metastasis, or severe late treatment toxicities, ultimately only 2 patients received a salvage node dissection within 6 months of follow-up time. Aside from 5 patients with local-regional failure received salvage surgery after definitive radiotherapy, most patients with first-line treatment failure were received chemotherapy or combining with targeted therapy. Chun et al. ^[19] suggest that salvage surgery after definitive radiotherapy should be considered for patients who show residual disease after 6 months, because residual tumors show progression soon after 6 months.

In patients undergoing surgical resection with or without postoperative adjuvant IMRT. Seventeen patients were observed regional lymph node failure, 10 of them were isolated nodal failure, 4 patients accompanied by local recurrence, and 3 patients accompanied by distant metastasis. Of the 17 patients with nodal failure, failures involved ipsilateral neck level II in 7 patients, levels III and VIb both in 4 patients, level VII in 5 patients. Furthermore, nodal failure involved in ipsilateral neck level IV and V was both one patient. Regarding 46 patients undergone lymph node dissection with 35 ips- and 11 bilateral neck dissection in this study. Six of them observed contralateral neck failure, with level II in 4 patients, level III in 3 patients, level VIb and VII both in one patient. Among these 6 patients, 5 patients had received postoperative radiation with radiation dose of 50–66Gy. Previously multi-center randomized clinical trials have confirmed post-operative radiation or chemoradiation improves loco-regional control and overall survival in the presence of extra-capsular nodal extension ^[7,8]. Although we fail to analyzed the reasons of node failure after surgery in our study, we found that the most commonly failure levels were the II (15.2%), III (8.7%), VIb (8.7%), and VII (10.9%). Comparing with patients receiving definitive radiotherapy, node failure rates at levels II and III were lower for patients receiving surgery as first-line treatment (15.2% vs. 24.7%; 8.7% vs. 13.0%), whereas, node failure at levels VIb and VII were exhibited higher ( 8.7% vs. 5.0%; 10.9% vs. 2.5%). The reason probably because the selective neck dissection always included the nodes in level II and III, whereas, the nodes in level VI and VII failed to remove from patients routinely in our study.

One retrospective study ^[13] include larynx (110 patients) and hypopharynx (26 patients) SCC undergoing total laryngectomy or pharyngolaryngectomy with neck dissection. Levels IIa and III were invaded in 28.7% and 25.7% of patients, respectively. Level VIb lymph-node involvement was 23.8% in patients who underwent level VIb neck dissection. Lymph-node recurrence rate was 10.3% in levels II to IV, and 13.2% in VIb. The author concluded that because high rate of involvement and recurrence of level VIb, systematic elective bilateral neck dissection might be needed. Previous retrospective studies ^[20,21] indicated that pyriform sinus apex or postcricoid invasion, or tumor diameter exceeding 3.5cm showed a trend in favor of paratracheal lymph node involvement. In our previous study, esophagus invasion was also highly correlated with increased risk of developing level VIb metastasis. It is noteworthy that lymph node at level VII (retropharyngeal lymph node) can not be removed routinely by surgery, and hardly be detected by imaging before surgery. Currently, there is no consensus regarding the delineation of lymphatic clinical target volume for post-operative radiation therapy for hypopharyngeal cancer. Based on results found in our study, irradiation of the level VII should be recommended, especially for the primary tumors originated from posterior pharyngeal wall (PPW), or PPW invasion ^[22,23].

The limitations of our study include its retrospective nature. The follow up time is relatively short. We did not perform the dosimetric analysis of the patterns of failure, and fail to confirm if CTV delineation is adequate. The prognosis associated factors for hypopharyngeal carcinoma could not be taken into account, including the evaluation of the surgical margins, perineural invasion, and nodal extracapsular extension.

Based on our results, we concluded that whatever the treatment modality, levels II and III in ipsilateral neck were most commonly failure regions. The regional cervical lymph node recurrence and persistent disease remained the major cause of failure following curative intent of definitive IMRT. Because of high rate of node failure of level VIb and VII after surgery, post-operative radiation field should be include these territories, particularly in the setting of locally advanced disease. Our results provide a clear rationale for efforts in the future aimed at improving local-regional control, which including accurate target volume delineation, optimal prescribed radiation dose and fraction, possibly identification areas of radio-resistance within the tumour. Further clinical research is needed to assess the utilization of IMRT combined with novel systemic agents in locally advanced hypopharynx SCC.

SCC: Squamous cell carcinoma

LMR: Lymphatic metastasis ratio

LMI: Lymphatic metastasis intensity

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Table 1. Patient, disease, and treatment characteristics

Characterisitis	N(%)
Age, years
Median (range)	58 (41-82)
Gender
Male	118 (95.9%)
Female	5 (4.1%)
Tumor site
Pyriform sinus	106 (86.2%)
Posterior pharyngeal wall	9 (7.3%)
Postcricoid area	8 (6.5%)
TNM stage
II	7 (5.7%)
III	25 (20.3%)
IV_a	83 (67.5%)
IV_b	8 (6.5%)
Clincal T stage
T₁	7 (5.7%)
T₂	19 (15.4%)
T₃	30 (24.4%)
T₄	28 (22.8%)
Pathological T stage
T₁	5 (5.7%)
T₂	12 (9.8%)
T₃	9 (7.3%)
T₄	13 (10.6%)
Clincal N stage
N₀	12 (9.8%)
N₁	16 (13.0%)
N_2a	2 (1.6%)
N_2b	26 (21.1%)
N_2c	19 (15.4%)
N₃	3 (2.4%)
Pathological N stage
N₀	6 (4.9%)
N₁	7 (5.7%)
N_2a	1 (0.8%)
N_2b	25 (20.3%)
N_2c	5 (5.7%)
N₃	1 (0.8%)
Surgery
Total laryngopharyngectomy and neck dissection	20 (16.3%)
Partial laryngopharyngectomy and neck dissection	20 (16.3%)
Isolated neck dissection	6 (4.9%)
Node dissection
Ipsilateral	35 (28.5%)
Bilateral	11 (8.9%)
Intensity-modulated radiotherapy
postoperative	40 (32.5%)
definitive	77 (56.9%)
Chemotherapy
Induction	54 (43.9%)
Concurrent	28 (22.8%)

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05 Sep, 2019

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Patterns of regional lymph node failure of locally advanced hypopharynx squamous cell carcinoma after first-line treatment with surgery and/or intensity-modulated radiotherapy

Status:

Journal Publication

Version 1

Abstract

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Background

Methods

Results

Discussion

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References

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Status:

Journal Publication

Version 1