PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.

Objective: This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Methods: Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. Conclusion: In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial.

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Laryngectomy plus postoperative radio(system)therapy versus primary radio(system) therapy for the treatment of locally advanced laryngeal and hypopharyngeal cancer - results from the University Clinical Cancer Registry Regensburg.

BACKGROUND: There are few adequate randomized clinical trials directly comparing the therapeutic options of primary laryngectomy (pLE) vs. primary radio(system)therapy (pR(S)T) in patients with locally advanced laryngeal and hypopharyngeal carcinoma and thus little clear scientific evidence to decide which patients will benefit most from which procedure. AIMS/OBJECTIVES: Aim was to compare survival between the therapeutic options and to learn from the limitations of this study, especially in the context of improved clinical assessment. MATERIAL AND METHODS: The clinical data of patients treated between January 2010 and February 2022 were obtained from the electronic database of the University Hospital Regensburg. Overall survival (OS) and progression-free survival (PFS) were compared between the treatment groups. RESULTS: The study included 193 patients (pLE n = 68, pR(S)T, n = 125). Median OS was 31.2 months and median PFS was 24.7 months with no significant difference between the treatment groups (p > .050). Patients who did not receive complete treatment as recommended by the tumor conference (n = 47, 24.4%) had a higher risk of death (p = .024). CONCLUSIONS AND SIGNIFICANCE: The results of our study are consistent with the survival data reported in the literature. More detailed systematic data in clinical routine (e.g. relevant comorbidities) are required to ensure guideline-based recommended therapy.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Matched-pair analysis of survival in patients with poorly differentiated versus well and moderately differentiated hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HPSCC) is among the most common malignances of the head and neck and is associated with a poor prognosis. Although both differentiation and tumor-node-metastasis stage affect tumor aggressiveness, the effect of differentiation on the prognosis of HPSCC at different stages is unclear. The aim of this study was to compare survival outcomes between patients with poorly differentiated versus well-differentiated and moderately differentiated HPSCC. Patients with well/moderately differentiated and poorly differentiated HPSCC were matched based on age, sex, smoking status, alcohol use, comorbidity score, tumor stage, and therapeutic strategies. The Kaplan-Meier curve and Cox proportional hazards model were used to analyze survival. A total of 204 patients with newly diagnosed HPSCC were included after matching 102 well/moderately differentiated cases and 102 poorly differentiated cases from Peking Union Medical College Hospital. Patients with well/moderately differentiated HPSCC had significantly better disease-specific survival (P = .003) and overall survival (P = .006) than patients with poorly differentiated HPSCC. Additionally, multivariable analysis indicated that increased differentiation was associated with a significantly reduced risk of overall death (adjusted hazard ratio, 0.51; 95% confidence interval, 0.34-0.78, P = .002), and death due to disease (adjusted hazard ratio, 0.44; 95% confidence interval, 0.28-0.69, P < .001). Survival outcomes differed significantly between the well/moderately differentiated and poorly differentiated HPSCC patients. Treatment strategies based on the level of pathological differentiation might be necessary to improve survival outcomes in patients with HPSCC.

Response-Adapted Treatment Following Radiotherapy in Patients With Resectable Locally Advanced Hypopharyngeal Carcinoma.

Importance: Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear. Objective: To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC. Design, Setting, and Participants: This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded. Exposures: Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT. Main Outcomes and Measures: Five-year overall survival and survival with a functional larynx. Results: Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively; P < .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39; P = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84, P = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%. Conclusions and Relevance: In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.

Prognostic Factors of Potential Early Recurrence of Hypopharyngeal Carcinoma.

BACKGROUND/AIM: Prognostic factors of hypopharyngeal carcinoma have been reported previously. However, recurrent cases of this disease occurring within 6 months of treatment have been excluded or poorly documented in many studies. We aimed to evaluate the prognostic factors of hypopharyngeal carcinoma recurrence within 6 months. PATIENTS AND METHODS: A total of 120 patients were eligible for this retrospective study. Recurrent cases of hypopharyngeal carcinoma occurring within 6 months of treatment were evaluated and compared with non-recurrent cases. RESULTS: Recurrence within 6 months was detected in 28/50 cases. In univariate analyses, classification markers (pT≥4a and cN≥2b) were statistically significant prognostic factors for early recurrence (p=0.04 and p=0.04, respectively); however, only pT≥4a was predictive of recurrence in multivariate analyses (p=0.02). CONCLUSION: Risk stratification according to the prognostic factor pT≥4a will allow physicians to identify patients who should be followed meticulously within the first 6 months.

Surgical treatment of T2-3 posterior hypopharyngeal carcinoma with preservation of laryngeal function.

BACKGROUND: Posterior hypopharyngeal carcinoma indicates a poor prognosis. Previous treatments predicted negative influence to the pronunciation and swallowing function. The present study focuses on improving survival rate while improving quality of life. AIM: To investigate on the surgical techniques of the preservation of laryngeal function of posterior hypopharyngeal carcinoma. METHODS: Eighteen patients with posterior hypopharyngeal carcinoma of T2-T3 were studied. All primary lesions were removed and the defects were repaired with the radial forearm free flap (RFFF). RESULTS: The 3-year overall survival rate was 51.9%. All patients could maintain daily caloric intake by feeding orally, and remove the gastric tube 28-61 days after operation. Assessed swallowing function by Fiberoptic endoscopic evaluations of swallowing. When eating solid food, 66.67% patients had food residue; no food entered airway, and all patients had Penetration-Aspiration Scale of level 1. As for liquid, 11.11% patients had level 5, 16.67% level 4, 27.78% level 2 and 44.44% level 1. CONCLUSIONS: By preserving the integrity of larynx and superior laryngeal nerve with repairing the defects of posterior wall of hypopharynx with RFFF, patients with T2 and T3 stage posterior hypopharyngeal carcinoma could live a better quality of life.

Prognostic significance of hypoxia-inducible factor-1α expression in advanced pharyngeal cancer without human papillomavirus infection.

OBJECTIVE: This study aimed to clarify the association between both hypoxia-inducible factor-1α and glucose transporter type-1 expression and survival outcome in advanced pharyngeal cancer without human papillomavirus infection. METHOD: Twenty-five oropharyngeal and 55 hypopharyngeal cancer patients without human papillomavirus infection were enrolled. All patients had stage III-IV lesions and underwent concurrent chemoradiotherapy or surgery. Hypoxia-inducible factor-1α and glucose transporter type-1 expression were investigated in primary lesions by immunohistochemistry. RESULTS: There were 41 and 39 cases with low and high hypoxia-inducible factor-1α expression, and 28 and 52 cases with low and high glucose transporter type-1 expression, respectively. There was no significant correlation between hypoxia-inducible factor-1α and glucose transporter type-1 expression. In univariate analysis, nodal metastasis, clinical stage and high hypoxia-inducible factor-1α expression, but not glucose transporter type-1 expression, predicted significantly worse prognosis. In multivariate analysis, hypoxia-inducible factor-1α overexpression was significantly correlated with poor overall survival, disease-specific survival and recurrence-free survival. CONCLUSION: High hypoxia-inducible factor-1α expression was an independent risk factor for poor prognosis for advanced human papillomavirus-unrelated pharyngeal cancer.

Presurgical platelet-lymphocyte ratio for prognosis in advanced hypopharyngeal squamous cell carcinoma in individuals undergoing radical resection.

BACKGROUND: Patient prognosis in hypopharyngeal carcinoma remains difficult to predict, necessitating new, readily available biomarkers. OBJECTIVE: Platelet-lymphocyte ratio (PLR)'s effects on recurrence-free survival (RFS) and overall survival (OS) were evaluated in individuals undergoing radical resection for advanced hypopharyngeal squamous cell carcinoma (HSCC). METHODS: A total of 89 patients were retrospectively assessed. PLR, and derived neutrophil-lymphocyte (dNLR) and neutrophil-lymphocyte (NLR) ratios were determined based on complete blood count. Then, the prognostic values of PLR, dNLR and NLR were assessed by univariate and multivariate Cox regression analyses adjusted for disease-specific prognostic factors. Endpoints of interest were RFS and OS. RESULTS: The optimal cutoff of PLR was 98.815, based on which individuals were categorized into the high- (PLR ≥98.815) and low- (PLR <98.815) PLR groups. High PLR (p = .022) had a significant association with reduced RFS, which still showed significance in multivariable analysis (HR = 2.020, 95%CI: 1.076-3.794, p = .029). In univariate analysis, PLR (p = .046) and positive surgical margin (p = .021) also had significant associations with OS. CONCLUSION: Elevated PLR has associations with increased risk of recurrence and reduced survival in advanced HSCC cases undergoing radical resection. High presurgical PLR may independently predict RFS. Therefore, further multi-institutional prospective studies are needed to better characterize the role of pre-operative blood PLR as prognostic factors in HSCC.

Detection of human papillomavirus infection in laryngeal and hypopharyngeal carcinoma using droplet digital PCR and its correlation with prognosis.

OBJECTIVE: To use droplet digital polymerase chain reaction (ddPCR) to detect human papillomavirus (HPV) infection in squamous cell carcinoma of the larynx and hypopharynx (SCCLHP) and to analyze its association with the prognosis of patients with HPV. METHODS: We used ddPCR for HPV detection in 114 patients with SCCLHP; clinical data were collected, and the patients were followed-up for prognosis analysis. Univariate and multivariate Cox regression analyses were used to complete the analysis of risk factors. This clinical study was registered (clinical trial registration no. ChiCTR2000033032). RESULT: Of the total cases, 15.79% (18/114) were HPV-positive and 8 (8/18, 44.4%) patients had tumors with HPV-16. There was a significant correlation between HPV-16 and the T classification and Tumor-Node-Metastasis (TNM) (P = 0.025 and 0.036, respectively). The 3-year overall survival rates in the HPV-positive and HPV-negative patients were 39.8% and 48.6% (P = 0.776), respectively. In the univariate analysis, HPV infection was not associated with the relative risk of progression (hazard ratio [HR] = 1.109, P = 0.778). Patients with laryngeal carcinoma (HR = 1.805, P = 0.037), no alcohol consumption (HR = 0.430, P = 0.009), well-differentiated tumors (HR = 2.570, p = 0.006), TNM I-II (HR = 2.482, P = 0.003), and no lymph node metastasis (HR = 2.615, P = 0.001) had better prognoses. In the multivariate analysis, tumor location (HR = 3.044, P = 0.001), alcohol consumption (HR = 0.474, P = 0.022), tumor differentiation (HR = 2.131, P = 0.030), and lymph node metastasis (HR = 4.179, P < 0.001) were independent predictors of better overall survival in SCCLHP. CONCLUSION: ddPCR is an advanced technology that can accurately diagnose HPV infection with high specificity and sensitivity. The HPV infection rate in SCCLHP was low, and there was no significant difference in the prognosis of SCCLHP.

To what extent has the last two decades seen significant progress in the management of older patients with head and neck cancer?

INTRODUCTION: Life expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS: Patient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged ≥60 years diagnosed with HNSCC in 1990-1995 and 2010-2015 were compared using chi-square test and relative survival analysis. RESULTS: Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p = 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease. CONCLUSION: Relative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed.

Survival and complications with a surgical approach in advanced hypopharyngeal cancer.

BACKGROUND AND OBJECTIVES: The treatment paradigm for advanced hypopharyngeal cancer has shifted from surgical approaches to organ preservation. However, recent studies indicated that surgical approaches may be associated with better survival rates. This study aimed to conduct a head-to-head comparison of survival outcomes and complications with surgical versus nonsurgical approaches using a nationwide database. METHODS: Using a nationwide data set, we gathered 2196 propensity score-matched patients with stage III/IVa hypopharyngeal cancer. We compared survival rates and complications among patients with surgical and nonsurgical cancer treatment. RESULTS: Patients with stage III and IVa hypopharyngeal cancer who underwent initial surgery had significantly better 5-year overall survival and disease-free survival rates compared to their nonsurgical counterparts. There were no significant differences in long-term complications with regard to swallowing. CONCLUSIONS: These results suggest that patients who underwent initial surgery for advanced hypopharyngeal cancers had better survival rates and equivalent long-term function.

High pretreatment platelet-to-lymphocyte ratio is related to poor prognosis in the squamous cell carcinoma of the larynx and hypopharynx in male patients.

BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.

Survival and function following pharyngo-laryngo-oesophagectomy in Wales: a twelve-year case series.

OBJECTIVE: Treatment of locally advanced hypopharyngeal cancer can cause significant morbidity and late toxicity. Pharyngo-laryngo-oesophagectomy can achieve adequate surgical margins, but data on survival and functional outcome are limited, especially in Wales. This study aimed to describe mortality, morbidity and functional outcome following pharyngo-laryngo-oesophagectomy in a Welsh population. METHOD: This study was a retrospective case note review of pharyngo-laryngo-oesophagectomy cases in Wales over 12 years. RESULTS: Fifteen patients underwent pharyngo-laryngo-oesophagectomy; all but one underwent gastric pull-up. Median survival and disease-free survival were 17 months (range, 2-53 months) and 14 months. Censored 3-month, 1-year and 3-year survival was 93, 71 and 50 per cent, respectively. Common Terminology Criteria for Adverse Events grading of long-term dysphagia was 1 in 58 per cent, 2 in 33 per cent and 3 in 8 per cent, and 87.5 per cent achieved a 'moderate' or 'good' voice rehabilitation. CONCLUSION: These results demonstrate favourable survival and reasonable functional outcome following pharyngo-laryngo-oesophagectomy, suggesting pharyngo-laryngo-oesophagectomy should be considered in all appropriate surgical candidates.

Risk stratification of postoperative recurrence in hypopharyngeal squamous-cell carcinoma patients with nodal metastasis.

PURPOSE: To explore lymph node-related risk factors and investigate the benefit of different adjuvant therapy strategies in hypopharyngeal squamous-cell carcinoma (HPSCC) patients with nodal metastasis (N +). METHODS: We conducted a retrospective review covering 266 HPSCC patients with nodal metastasis. Kaplan-Meier curves and Cox proportional hazard models were utilized to evaluate recurrence-free survival (RFS) and independent risk factors. RESULTS: pT3-T4, extranodal extension, lymphovascular invasion, and lower lymph node involvement were high-risk factors leading to poorer RFS in N + HPSCC patients. Patients were classified into three groups based on the recursive-partitioning analysis (RPA). Postoperative chemoradiation significantly improved RFS in patients in the high-risk group (p < 0.001). For patients in the low- and intermediate-risk groups, the application of adjuvant therapies showed no significant benefit on RFS (p = 0.74 and 0.53, respectively). CONCLUSIONS: The novel risk stratification for N + HPSCC patients can predict the risk of postoperative recurrence effectively. Adjuvant chemoradiation is preferred for patients in the high-risk group as it lowers risk of recurrence. Conversely, for patients in the low- and intermediate-risk groups, regular observation and follow-up strategies are a valid form of treatment.

Improved Tumor Control Related to Radiotherapy Technological Development for Hypopharyngeal Cancer.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS: Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS: One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P < .001) beginning in the 2000s. The 24-month FFLR using two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and intensity-modulated RT (IMRT) was 52%, 55%, and 80%, respectively; 24-month PFS was 39%, 46%, and 73%, respectively; and 24-month OS was 27%, 40%, and 68%, respectively. OS (P = .01), PFS (P = .03), and FFLR (P = 0.02) were improved with IMRT over 2D-RT, and FFLR appeared to be improved over 3D-CRT (P = .06). Controlling for chemotherapy use and other major variables, IMRT produced a strong influence over FFLR (adjusted hazard ratio [HR] = 0.2, 95% confidence interval [CI]: 0.0-1.2, P = .08) and a benefit in OS (adjusted HR = 0.1, 95% CI: 0.0-0.4, P = .005). CONCLUSIONS: Across 6 decades, patient and tumor characteristics remained similar whereas use of chemoradiation increased and IMRT was adopted. The introduction of IMRT was associated with improved FFLR, PFS, and OS, and a reduction in acute toxicity as compared to earlier radiation technologies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E452-E458, 2021.