Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.

/pdf/tumour-inflammation-signature-and-expression-of-s100a12-and-ao5bgoe8sg.pdf

Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer.

Background Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis. Methods All randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments. Results DC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08-0.73), 0.43 (0.24-0.77), and 0.54 (0.27-1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24-0.88), 0.51 (0.34-0.77), and 0.49 (0.20-1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively. Conclusions Given its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

/pdf/the-most-efficacious-induction-chemotherapy-regimen-for-1jwwjih7ra.pdf

The Most Efficacious Induction Chemotherapy Regimen for Locoregionally Advanced Nasopharyngeal Carcinoma: A Network Meta-Analysis

Background There is uncertainty in the treatment options for resectable hypopharyngeal squamous cell carcinoma. Methods A systematic review of randomised controlled trials (RCTs) was performed. Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index, and Conference Proceedings databases and trial registries were searched until November 2020 for randomized controlled trials performed on resectable hypopharyngeal squamous cell carcinoma. Two systematic review authors independently identified studies and extracted data. The primary outcomes evaluated were overall survival, disease-free survival, any recurrence, local recurrence, loco-regional recurrence, distal recurrence and laryngectomy-free survival. The secondary outcomes were response rates following neoadjuvant treatment and comparison of treatment-related toxicity. Assessment of risk of bias was performed for the selected studies using Cochrane’s tool for assessing risk of bias. The studies were evaluated for the quality of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Risk ratios (RR), rate ratios, and hazard ratios (HR) were calculated along with 95% confidence intervals (95% CI). The Meta-analysis was performed using a random-effects model. Results Five RCTs met the inclusion criteria for this review. The risk of bias was unclear or high for the trials. Non-organ preservation(n = 140) versus organ preservation (n = 144) (two trials): no statistically significant difference could be identified for any of the primary outcomes. Concurrent chemoradiotherapy (n = 37) versus sequential chemotherapy followed by radiotherapy (n = 34) (one trial): no statistically significant difference was noted between the two treatment arms for overall survival, disease-free survival and loco-regional recurrence. Laryngectomy-free survival was found to be superior in concurrent chemoradiotherapy arm (HR:0.28, 95% CI 0.13, 0.57). Induction chemotherapy followed by concurrent chemoradiotherapy (n = 53) versus induction chemotherapy followed by radiotherapy (n = 60) (one trial): no statistically significant difference was noted between the treatment arms for overall survival, disease-free survival and laryngectomy-free survival. Preoperative radiotherapy (n = 24) versus postoperative radiotherapy (n = 23) (one trial): overall survival was found to be better in the postoperative radiotherapy arm (HR:2.44, 95% CI1.18, 5.03). No statistically significant difference was noted in terms of treatment-related toxicity. Conclusions There are considerable uncertainties in the management of resectable hypopharyngeal cancer. Trail registration PROSPERO registration: CRD42019155613.

/pdf/treatment-options-for-resectable-hypopharyngeal-squamous-3oa5i233.pdf

Treatment options for resectable hypopharyngeal squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy.239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS).HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%.The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation. 

https://link.springer.com/content/pdf/10.1007/s00405-022-07668-1.pdf

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy

Backround: The purpose of this study was to evaluate the outcomes of different radiotherapy techniques used in routine clinical practice for the radical treatment of hypopharyngeal cancer and to assess improvements over the last few decades. Methods: We compared the outcomes of patients with hypopharyngeal squamous cell carcinoma treated with curative radiotherapy (RT) or chemoradiotherapy between January 1992 and December 2020, using 2D-RT, 3D-CRT/IMRT, and VMAT techniques. A retrospective analysis was conducted on eighty-one patients with hypopharyngeal cancer. Results: The median follow-up time was 26 months (range: 6-290). In multivariate analysis, radiotherapy technique, Karnofsky Performance Status (KPS), nodal stage, and clinical stage were identified as statistically significant factors affecting overall survival and local-regional relapse-free survival. Grade 2-4 early and late side effects were significantly more frequent in Group I patients (treated with 2D Conventional Radiotherapy) (20.3%) compared to Group II patients (treated with 3DCRT/IMRT and VMAT techniques) (3.1%) Conclusion: KPS, stage, and advanced RT techniques independently significantly affected outcomes. Moreover, advanced RT techniques were associated with a significant reduction in side effects. 

Improvement of Outcomes over the Last Decades in Hypopharyngeal Carcinoma Treated by Radical Radiotherapy

Hypopharyngeal and laryngeal neoplasms are both fatal and hard to catch in early stages. Yet which treatment is the most efficacious one still remain unanswered. This network meta-analysis (NMA) was conducted to investigate effectiveness of six therapies being utilized in clinical practice nowadays. PubMed and Embase were retrieved to synthesize data. Direct and indirect evidence was combined to compare efficacy of treatments. A relative ranking of the six regimens was calculated by the surface under the curve ranking area (SUCRA). A total of 28 trials with 9109 patients were included in our NMA. Five endpoints investigated included 3/5-year overall survival (3/5-OS), 3/5-year disease free survival (3/5-DFS) and 5-year overall survival rate (5-OSR). In terms of all efficacy outcomes, radiotherapy combined with surgery (RT + S) proved to be better than other therapies while radiotherapy (RT) alone also performed well. Induction chemoradiotherapy (ICRT) was the best regarding 3-DFS (SUCRA = 0.846) while current chemoradiotherapy (CCRT) ranked first in 5-DFS (SUCRA = 0.933) according to SUCRA results. No significant differences were demonstrated in 5-DFS and 5-OSR as shown in the results of NMA. RT combined with surgery turned out to be optimal therapy of all the outcomes while the efficacy of RT was relatively poorer in the treatment of patients with larynx stage III-IV and hypopharynx stage II-IV. Also, the good performance of CCRT and ICRT in terms of DFS made them as secondary recommended therapies. There is no significant difference between surgery and transoral laser microsurgery (TLM) alone.

/pdf/comparative-efficacy-of-six-therapies-for-hypopharyngeal-and-1ioid9s4ek.pdf

Comparative efficacy of six therapies for Hypopharyngeal and laryngeal neoplasms: a network meta-analysis.

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Comparative efficacy of six therapies for Hypopharyngeal and laryngeal neoplasms: a network meta-analysis.