Advanced Hypopharyngeal Cancer Research Articles

The Emergence of Tumor-Initiating Cells in an Advanced Hypopharyngeal Tumor Model Exhibits Enhanced Angiogenesis and Nuclear Factor Erythroid 2-Related Factor 2-Associated Antioxidant Effects.

Aims: Hypopharyngeal cancer (HPC) is associated with the worst prognosis of all head and neck cancers and is typically identified in an advanced stage at the time of diagnosis. While oxidative stress might contribute to the onset of HPC in patients using tobacco or alcohol, the extent of this influence and the characteristics of HPC cells in advanced stage remain to be investigated. In this study, we explored whether HPC cells survived from necrotic xenograft tumors at late stage would display increased tumor resistance along with altered tolerance to oxidative stress. Results: The remnant living HPC cells isolated from a late-stage xenograft tumor, named FaDu ex vivo cells, showed stronger chemo- and radioresistance, tumorigenesis, and invasiveness compared with parental FaDu cells. FaDu ex vivo cells also displayed increased angiogenic ability after re-transplantation in mice visualized by invivo near infrared-II fluorescence imaging modality. Moreover, FaDu ex vivo cells exhibited significant tumor-initiating cell (TIC)-related properties accompanied by a reduction of the level of reactive oxygen species, which was associated with the upregulation of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Interestingly, inhibition of Nrf2 by the RNA interference and the chemical inhibitor could reduce the TIC-related properties of FaDu ex vivo cells. Innovation: Oxidative stress potentially initiates HPC, but elevation of Nrf2-associated antioxidant mechanisms would be essential to mitigate this effect for promoting and sustaining the stemness of HPC at the advanced stage. Conclusion: Present data suggest that the antioxidant potency of advanced HPC would be a therapeutic target for the design of adjuvant treatment.

Abstract 3741: Helper/killer hybrid epitope long peptide (H/K-HELP) cancer vaccine augments Th1-dependent CTL induction at tumor-draining lymph node to eradicate solid tumor: its application to develop an innovative combination cancer immunotherapy(iCCI)

Abstract We have initially demonstrated the pivotal role of IFN-γ-producing tumor-antigen-specific Th1 cells for the complete eradication of established tumor mass by CTL. The accumulated evidence has clearly demonstrated that induction of Th1-dependent full activation of CTL at tumor-draining lymph nodes (TDLN) are crucial for inducing complete rejection of solid tumor by CTL. To induce Th1 immunity efficiently at TDLN in tumor-bearing host, we developed an artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which conjugated killer and helper epitope peptides of cancer antigen by a glycine-linker. In mouse model, OVA-H/K-HELP was selectively presented in vivo by professional DC in vaccinated TDLN and sustained antigen presentation capability of DC to stimulate both CTL and Th1 cells. Thus, in contrast to short peptide, vaccination of OVA-expressing EG7-bearing mice with OVA-H/K-HELP caused a complete eradication of EG7 tumor mass. To apply these basic findings to clinical treatment of cancer patients, we then developed Survivin-H/K-HELP. Treatment of a patient with a triple-negative breast cancer patient with Survivin-H/K-HELP induced a complete response in a triple-negative breast cancer patient concomitantly with the induction of Th1-dependent cellular and humoral immune responses. In this clinical study, the patients showed Th1-dependent C’-fixing IgG antibody production and exhibited IFN-γ-producing Th1 cellular responses. Finally, we also applied H/K-HELP-pulsing DC-vaccine to develop an innovative combination cancer immunotherapy (iCCI). The iCCI consisting of radiation, low dose of immune check point inhibitors (ICIs:Nibolumab, Ipilimumab) and H/K-HELP-pulsed DC, all of which have been shown to initially modulate antitumor immunity at TDLN. Here, we described a successful outcome of a case of the stage IVA inoperable advanced hypopharyngeal squamous cell cancer patient with lymph node-metastasis. The iCCI treatment of the patient caused a complete disappearance of all cancers and the patient has been cancer free for over 15 months so far. Although the destruction mechanism of cancer is not determined, we image this iCCI might improve patient’s antitumor immune capability in immune microenvironment around tumor (IMAT) including TDLN and TME. Our developed iCCI will become a promising strategy to overcome inoperable advanced cancers in future. Citation Format: Takanori Iwasaki, Yuichiro Yazaki, Takashi Masuko, Takashi Nishimura. Helper/killer hybrid epitope long peptide (H/K-HELP) cancer vaccine augments Th1-dependent CTL induction at tumor-draining lymph node to eradicate solid tumor: its application to develop an innovative combination cancer immunotherapy(iCCI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3741.

Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer.

To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.

A case report of cutanenous metastasis in locally advanced hypopharyngeal cancer

Cutaneous metastasis from head and neck cancers are uncommon, accounting for less than 1% for distant metastasis in head and neck cancers. It can be single and discrete or it may present as multiple lesions at different anatomic sites. There is a correlation between the frequency of cutaneous metastasis and the type and prevalence of primary cancer. Head and neck squamous cell carcinomas are aggressive tumors with metastasis occurring in up to 15-20% cases. However, they rarely metastasize to skin and the reported incidence is about 0.8-1.3%. Very few cases of distant cutaneous head and neck SCC (HNSCC) metastases have been described and are usually multiple. Underreporting is likely in cases of simultaneous occurrence with lung, bone and brain metastases. Cutaneous distant metastases signify a poor prognosis and 1-year survival is 0%.

Aesthetic Considerations of Simultaneous Reconstruction With Free Flap for Local Advanced Hypopharyngeal Combined With Cervical Esophageal Cancer.

Patients with local advanced hypopharyngeal combined with esophageal cancer often require total laryngectomy and cervical esophagectomy, which result in big-sized upper aerodigestive tract defects and neck deformities. Although free flap is widely used to reconstruct aerodigestive defects, the aesthetic results especially that of neck contour have not brought to the forefront or discussed extensively. This article aims to report the preliminary aesthetic results of free flap reconstruction for local advanced hypopharyngeal cancer combined with cervical esophageal cancer defects, highlighting the thickness of subcutaneous fat of the flap. A retrospective study of 21 patients with local advanced hypopharyngeal combined with cervical esophageal cancer from July 2010 to August 2022 was conducted. After completing total laryngectomy, bilateral neck dissection, and removal of the tumor with safe margin, a free thigh flap of subcutaneous fat greater than 1 cm in thickness was used to reconstruct the hypopharyngeal and cervical esophageal defects. In addition to general demographic, oncological, and reconstructive data, preoperative and postoperative neck circumferences were recorded and compared. A subjective questionnaire survey was conducted on patients' satisfaction with postoperative neck contour. The patients were followed up from 3 to 10 years, with an average of 3 years. There were 2 cases (2/21) of free flap loss because of flap necrosis and secondary repair with a pedicled pectoralis major flap. Nineteen flaps (19/21) survived. Three cases (3/21) developed a pharyngeal fistula and one case (1/21) experienced salivary fistula, all of the fistulae healed after drainage and dressing change. There was a relatively high satisfaction rate among patients (16/21) with the postoperative neck contour. A paired sample t test showed no statistically significant difference between the preoperative and postoperative values ( t = 2.002, P > 0.05). Patients with a thicker subcutaneous fat flap (≥1.5 cm) had a more symmetrical and fuller neck contour during long-term postoperative follow-up. The application of a fat-rich subcutaneous free thigh flap to reconstruct the defect of local advanced hypopharyngeal combined with cervical esophageal cancer can achieve better neck aesthetic contour.

Background Factors Associated with Postoperative Complications in Patients with Advanced Hypopharyngeal Cancers Undergoing Total Pharyngolaryngoesophagectomy Followed by Free Jejunal Flap Reconstruction

AbstractWe retrospectively analyzed background factors associated with postoperative complications in patients with advanced hypopharyngeal cancers who underwent total pharyngolaryngectomy followed by free jejunal flap reconstruction. A total of 23 participants, including 21 men and 2 women aged 49 to 83 years (average 72.3 years) were enrolled in this study. Mild and moderate/severe complications occurred in five and seven cases, respectively. The most common complication was stricture of the esophagojejunal anastomosis (nine cases). Other complications included two tracheostomal stenosis, one each for pneumonia and chyle leakage. The free jejunal flap survived in all cases. The disease-free survival rate was 47.8% at 52 weeks after surgery. The platelet count was significantly lower (18.8 ± 1.9 × 104/mL vs. 27.7 ± 1.8 × 104/mL; p = 0.008) in patients with moderate/severe complications than in those without. The percentage of stage IV cases and intraoperative blood loss tended to be higher in patients with complications than in those without. Knowledge of these potential risk factors for the development of postoperative complications to satisfactorily manage the clinical course of patients with advanced hypopharyngeal cancers is necessary.

Radiomics analysis for the prediction of locoregional recurrence of locally advanced oropharyngeal cancer and hypopharyngeal cancer.

By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.

392TiP A prospective phase II study of individualized adjuvant therapy in patients with locally advanced hypopharyngeal cancer after neoadjuvant therapy

392TiP A prospective phase II study of individualized adjuvant therapy in patients with locally advanced hypopharyngeal cancer after neoadjuvant therapy

Coiled tube of femoral anterolateral flap for repair of circumferential defect after operation of advanced hypopharyngeal carcinoma

Objective: To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma. Methods: Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up. Results: The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%. Conclusion: Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.

Matched-pair analysis of the impact of low-dose postoperative radiotherapy on prognosis in patients with advanced hypopharyngeal squamous cell carcinoma without positive surgical margins and extracapsular extension.

We conducted a comparative analysis between low and high-dose postoperative radiotherapy in patients with hypopharyngeal squamous cell carcinoma (HPSCC) in stage III or IV without positive surgical margins and extracapsular extension (ECE). Propensity score matching (PSM) was used to eliminate confounding factors and reduce bias. The matched-pair analysis included 156 patients divided into two groups: the low-dose radiotherapy group (LD-RT 50 Gy, 78 cases) and the high-dose radiotherapy group (HD-RT 60 Gy, 78 cases). Both cohorts were statistically comparable in terms of age, gender, subsite, and TNM classification. The median follow-up time was 49 months (ranging from 5 to 100 months). The overall survival (OS) rate, progression-free survival (PFS) rate, locoregional control rate (87% vs. 85.7%; p = 0.754), distant metastases-free survival (79.2% vs. 76.6%; p = 0.506), and the occurrence of second primary tumors (96.1% vs. 93.5%; p = 0.347) showed no significant differences between the LD-RT group and the HD-RT group. The 3-year OS was 64.9% and 61% in the low-dose and high-dose group, respectively, and 63% in the entire group (p = 0.547). The 3-year PFS was 63.6% and 54.5% (p = 0.250), respectively, and the 3-year PFS of the entire group was 59.1%. Multivariate analyses revealed that pathological T and N classification, and pathological differentiation were associated with 3-year OS, PFS, and LRFS and were independent prognostic factors (p < 0.05). LD-RT was not associated with an increased risk of death and disease progression compared to HD-RT. The results of postoperative low-dose radiotherapy did not show inferiority to those of high-dose radiation for patients with advanced hypopharyngeal cancer without positive surgical margins and ECE in terms of OS, PFS, locoregional control, and metastases-free survival.

Pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction.

Total laryngeal and hypopharyngeal resection remained to be the mainly treatment option for advanced hypopharyngeal cancer, which resulted in complicated reconstructive challenge for circumferential hypopharyngeal defect. The pedicled thoracoacromial artery compound flaps included Thoracoacromial artery perforator (TAAP) flap and pectoralis major myocutaneous (PMMC) flap. This study is to evaluate the clinical application of the pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction. From May 2021 to April 2022, four hypopharyngeal cancer patients with circumferential hypopharyngeal defects were reconstructed by the pedicled thoracoacromial artery compound flaps. All patients were males. Patient age ranged from 35 to 62years (average, 50years). The Shoulder function were evaluated by SPADI. The average follow-up was 10.25months (range from 4 to 18months). All of the pedicled thoracoacromial artery compound flaps in our study survived. The defect length between tongue base and cervical esophagus ranged from 8 to 10cm after total laryngeal and hypopharyngeal resection. The TAAP flap size ranged from 6 × 7cm to 7 × 10cm, and the PMMC flap size ranged from 6 × 7cm to 9 × 12cm. The pedicle length of TAAP and PMMC flaps varied, respectively, from 5 to 8cm (mean 6.5cm) and 7cm to 11cm (mean 8.75cm). The mean time of TAAP and PMMC flaps harvest was, respectively, 82min and 39min. All patients were able to resume soft diet in the fourth week of postoperation, but one patient was operated by gastrostomy in the second month of postoperation because of pharyngeal cavity stenosis, and the patient successfully resumed oral soft diet by endoscopic balloon dilation after postoperation radiotherapy. All patients have resumed oral feeding at last. There were mild dysfunction for our patients according to SPADI during the mid-long follow-up. The pedicled thoracoacromial artery compound flaps have stable blood supply and provide adequate muscle coverage for greater protection during radiotherapy, and the microsurgical skills have no requirement. Therefore, the compound flaps provide a good choice for the reconstruction of circumferential hypopharyngeal defect, especially in the aged or patients with comorbidities who are not able to tolerate prolonged surgery.

Efficacy and safety of nab-paclitaxel+cisplatin/nedaplatin + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer.

e18050 Background: Targeted therapy and immunotherapy are efficacious treatment options for advanced head and neck cancer. However, the treatment of locally advanced hypopharyngeal carcinoma still consists of surgery, radiotherapy, and chemotherapy. Combining docetaxel, cisplatin (DDP), and 5-fluorouracil as standard induction chemotherapy provided opportunities for further surgical larynx preservation in some patients. This study retrospectively analyzed the short-term efficacy and adverse events of nab-paclitaxel + DDP/nedaplatin (NDP) + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer. Methods: The study included 22 patients with locally advanced hypopharyngeal cancer treated via induction chemotherapy at the Affiliated Hospital of Guilin Medical University from December 2020 to July 2022. Among these patients, 11 received nab-paclitaxel (125mg/m2, days 1 and 8) + DDP (35- 40mg/m2, days 1-2) or NDP (65-75mg/m2, day 1) + S-1 (30-40 mg/m2 bid, days 1-14) every 21 days for a total of three cycles. A baseline enhanced magnetic resonance imaging (MRI) of the head and neck was performed for all patients to confirm the presence of suspicious lesions. Another MRI was performed before the third cycle of induction chemotherapy to confirm the efficacy of the treatment regimen. Patients, who were responsive to the induction therapy, were allowed to choose their respective sequential therapy regimen. The response was assessed using RECIST v1.1. Adverse reactions were evaluated according to CTCAE5.0. Results: The response to treatment of the 11 patients was assessed by the investigators. There was one patient with a complete response (9.1%), eight patients with a partial response (72.7%), and two patients with stable disease (18.2%). The objective response rate was 81.8% (9/11), and the disease control rate was 100%. Five of the nine patients with a partial or complete response opted for surgery after three cycles of induction chemotherapy. The pathological complete response rate was 100% (5/5). The most common grade 3 treatment-emergent adverse events (TEAE) were leukopenia (45.5%), neurotoxicity (36.3%), and anemia (18.2%). Grade 4/5 TEAEs were not observed. Conclusions: Based on the results of this retrospective study, the nab-paclitaxel + DDP/ NDP + S-1 was a safe and viable induction chemotherapy regimen for locally advanced hypopharyngeal cancer. It allowed more options for subsequent treatment. Further research is warranted to validate the findings of this study. [Table: see text]

Toxicity Outcome of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy versus Concurrent Chemoradiotherapy Alone for Locally Advanced Hypopharyngeal Cancer

Background: Concurrent chemoradiation has emerged as a mainstay of treatment for locally advanced hypopharyngeal cancer (stage III to IVB). However, induction chemotherapy is still an area of ongoing interest in attempt to decrease the likelihood of emergence of distant metastases, improve loco-regional control and support organ preservation. Method: This quasi-experimental study was carried out among 86 patients of locally advanced hypopharyngeal cancer patients from November 2021 to October 2022 and distributed into two different groups. Group A received induction chemotherapy (IC) with Paclitaxel and Carboplatin followed by concurrent chemoradiotherapy (CCRT) and group B received CCRT alone. Patients were assessed in every 3 weeks during induction chemotherapy after each cycle and weekly during chemoradiotherapy to assess toxicities. Result: Final assessment was done at 12 weeks after completion of treatment. Most commonly observed toxicities were skin toxicity, oral mucositis, dryness of mouth and neurotoxicity. Patients in both groups mainly developed grade 2 skin toxicity and oral mucositis (44.2% vs 34.9% and 45.6% vs 39.5% in group A and B respectively). However, grade 2 dryness of mouth was observed among twenty patients in group A and eighteen patients in group B. Similarly, grade 1 neuropathy was mostly seen in both the group (41.86% vs 25.58% in group A and B respectively), but statistically not significant (p&gt;0.05). 17(39.53%) and 05(11.63%) patients participated in group A developed grade 1 and grade 2 nephrotoxicity respectively, whereas 15(34.88%) and 03(06.98%) patients developed grade 1 and grade 2 nephrotoxicity respectively in group B. Statistically in significant (p&gt;0.05). Hematological toxicity was also seen frequently in both the arms but statistically insignificant. Conclusion: All skin toxicity, oral mucositis, dryness of mouth, neurotoxicity and hematological toxicity were comparable between the two arms. The toxicities were acceptable ....

Developing a predictive nomogram and web-based survival calculator for locally advanced hypopharyngeal cancer: A propensity score-adjusted, population-based study.

Understanding the clinical features and accurately predicting the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) is important for patient centered decision-making. This study aimed to create a multi-factor nomogram predictive model and a web-based calculator to predict post-therapy survival for patients with LA-HPSCC. A retrospective cohort study analyzing Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for patients diagnosed with LA-HPSCC was conducted and randomly divided into a training and a validation group (7:3 ratio). The external validation cohort included 276 patients from Sichuan Cancer Hospital, China. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was used to identify independent factors associated with overall survival (OS) and cancer-specific survival (CSS), and nomogram models and web-based survival calculators were constructed. Propensity score matching (PSM) was used to compare survival with different treatment options. A total of 2526 patients were included in the prognostic model. The median OS and CSS for the entire cohort were 20 (18.6-21.3) months and 24 (21.7-26.2) months, respectively. Nomogram models integrating the seven factors demonstrated high predictive accuracy for 3-year and 5-year survival. PSM found that patients who received surgery-based curative therapy had better OS and CSS than those who received radiotherapy-based treatment (median survival times: 33 months vs 18 months and 40 months vs 22 months, respectively). The nomogram model accurately predicted patient survival from LA-HPSCC. Surgery with adjuvant therapy yielded significantly better survival than definitive radiotherapy. and should be prioritized over definitive radiotherapy.

A case of advanced hypopharyngeal cervical esophageal cancer treated by curative resection with management of tracheoesophageal fistula

Advanced esophageal cancer with tracheal invasion is fatal due to airway narrowing and the possibility of tracheoesophageal fistula (TEF) formation during the treatment process. If a TEF develops, palliative care is often chosen. It is very rare that curative treatment is performed including with chemoradiotherapy (CRT) or surgery in such cases. A 71-year-old man presented with dysphagia. He was diagnosed as having hypopharyngeal and cervical esophageal cancer with severe airway stenosis (cT4b [main bronchus, thyroid] N3 M0 cStage IIIC), and we initially created a tracheostomy. Second, we chose induction chemotherapy to avoid fistula formation by CRT, but after one course of chemotherapy, he developed a TEF due to remarkable tumor shrinkage. We strictly managed both his airway and nutrition by continuous suctioning over the cuff of the tracheal cannula and prohibiting swallowing of saliva and enteral nutrition via nasogastric tube. After three courses of chemotherapy were administered, we performed pharyngo-laryngo-esophagectomy followed by adjuvant chemotherapy. The patient remains alive and recurrence free at 9 years postoperatively. In cases of upper TEF caused by advanced hypopharyngeal and cervical esophageal cancer, radical treatment may be possible by effective induction chemotherapy combined with strict airway and nutritional management after prior tracheostomy.

Docetaxel-Cisplatin-Fluorouracil Induction Chemotherapy for Larynx Preservation in Patients with Locally Advanced Hypopharyngeal Cancer: Predictive Factors of Oncologic and Functional Outcomes.

The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

Prognostic Value of Controlling Nutritional Status Score in Advanced Hypopharyngeal Cancer.

The purpose of this study was to investigate the prognostic significance of the preoperative controlling nutritional status (CONUT) score in patients with resectable advanced hypopharyngeal cancer. This retrospective study included 113 advanced hypopharyngeal cancer patients who underwent curative resection in our hospital from 2013 to 2017. The association between the CONUT score and clinicopathological variables was evaluated. The association between CONUT score and survival was analyzed using Kaplan-Meier survival curves and Cox regression. The efficacy of the CONUT score and other immune-nutritional markers to predict prognosis was compared using a time-dependent receiver operating characteristic (ROC). Patients were divided into the high-CONUT score group (≥3) and the low-CONUT score group (≤2) according to ROC analysis. The CONUT score was associated with body mass index (p=0.047), monocyte (p=0.021), pharyngocutaneous fistula (p=0.045), flap repairment (p=0.034), tumor (T) classification (p=0.034), node (N) classification (p=0.036), subsite of tumor (p=0.035), and negative pathologic factors (p < 0.001). Tumor, node, metastasis (TNM) stage, negative pathologic factors, adjuvant radiotherapy, postoperative chemoradiotherapy, and CONUT score were independent prognostic factors for survival. Patients with a higher CONUT score had worse overall survival (OS) (hazard ratio: 2.76, 95% confidence interval [CI]: 1.44-5.29, p=0.002) and disease-free survival (hazard ratio: 2.51, 95% CI: 1.28-4.91, p=0.007). The area under the curve of the CONUT score (0.799) to predict 5-year OS wasgreater than those of Preoperative Nutritional Index (0.769), platelet-to-lymphocyte ratio (0.643), neutrophil-to-lymphocyte ratio (0.565), and lymphocyte-to-monocyte ratio (0.577). The CONUT score is a prognostic marker for patients with resectable advanced hypopharyngeal cancer. 3 Laryngoscope, 133:2613-2620, 2023.

MRI Radiomics for Predicting Survival in Patients with Locally Advanced Hypopharyngeal Cancer Treated with Concurrent Chemoradiotherapy.

A reliable prognostic stratification of patients with locally advanced hypopharyngeal cancer who had been treated with concurrent chemoradiotherapy (CCRT) is crucial for informing tailored management strategies. The purpose of this retrospective study was to develop robust and objective magnetic resonance imaging (MRI) radiomics-based models for predicting overall survival (OS) and progression-free survival (PFS) in this patient population. The study participants included 198 patients (median age: 52.25 years (interquartile range = 46.88-59.53 years); 95.96% men) who were randomly divided into a training cohort (n = 132) and a testing cohort (n = 66). Radiomic parameters were extracted from post-contrast T1-weighted MR images. Radiomic features for model construction were selected from the training cohort using least absolute shrinkage and selection operator-Cox regression models. Prognostic performances were assessed by calculating the integrated area under the receiver operating characteristic curve (iAUC). The ability of radiomic models to predict OS (iAUC = 0.580, 95% confidence interval (CI): 0.558-0.591) and PFS (iAUC = 0.625, 95% CI = 0.600-0.633) was validated in the testing cohort. The combination of radiomic signatures with traditional clinical parameters outperformed clinical variables alone in the prediction of survival outcomes (observed iAUC increments = 0.279 [95% CI = 0.225-0.334] and 0.293 [95% CI = 0.232-0.351] for OS and PFS, respectively). In summary, MRI radiomics has value for predicting survival outcomes in patients with hypopharyngeal cancer treated with CCRT, especially when combined with clinical prognostic variables.

Induction TPF followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locally advanced hypopharyngeal cancer: a preliminary analysis of a randomized phase 2 trial

PurposeConcurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma.Methods and materialsPatients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS), distant metastasis-free survival (DMFS), and toxicities.ResultsUltimately, 113 of the 142 patients were analyzed. With a median follow-up of 45.6 months (interquartile range 26.8–57.8 months), the 3-year OS was 53.1% in the IC + CCRT group compared with 54.8% in the CCRT group (hazard ratio, 1.004; 95% confidence interval, 0.573–1.761; P = 0.988). There were no statistically significant differences in PFS, DMFS, and the larynx-preservation rate between the two groups. The incidence of grade 3–4 hematological toxicity was much higher in the IC+ CCRT group than in the CCRT group (54.7% vs. 10%, P < 0.001).ConclusionsAdding induction TPF to CCRT did not improve survival and the larynx-preservation rate in locally advanced hypopharyngeal cancer, but caused a higher incidence of acute hematological toxicities.Trial registrationClinicalTrials.gov, number NCT03558035. Date of first registration, 15/06/2018.

Prognostic impact of the number of metastatic lymph nodes after surgery in locally advanced hypopharyngeal cancer

BackgroundPostoperative chemoradiotherapy (CRT) is a standard therapy for patients with high-risk factors for head and neck squamous cell carcinoma, including positive margin and extra-nodal extension (ENE). However, the prognostic impact of the number of pathological metastatic lymph nodes (pLNs) in hypopharyngeal carcinoma (HPC) is unclear. Thus, this study aimed to investigate postoperative prognostic factors for locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) with a focus on the number of pLNs.MethodsWe retrospectively analyzed medical records of 99 consecutive patients with LA-HPSCC who underwent total pharyngo-laryngo-esophagectomy (TPLE) and bilateral neck dissection (ND) between December 2002 and May 2019.ResultsThe median follow-up time for all censored patients was 63.2 months. The median overall survival (OS) was 101.0 months (95% confidence interval [CI] 48.1–134.9). patients had pLNs ≥ 3. Forty-six (45.5%) patients were diagnosed with ENE. Twenty (20.2%) patients received postoperative CRT. The multivariate analysis revealed that pLNs ≥ 3 (median OS: 163.2 vs. 31.8 months, hazard ratio [HR] 2.39, 95% CI 1.16–4.94, p < 0.01) and ENE (median OS: 161.0 vs. 26.3 months, HR 4.60, 95% CI 2.26–9.36, p < 0.01) were significantly associated with poor prognosis and that postoperative CRT (HR 0.34, 95% CI 0.16–0.72, p < 0.01) was significantly associated with better prognosis. The cumulative incidence of distant metastasis was higher in patients with pLNs ≥ 3 than in those with pLNs < 3 (p < 0.01).ConclusionpLNs ≥ 3 and ENE were significant poor prognostic factors for patients with LA-HPSCC who underwent TPLE and bilateral ND.