Elderly Head-and-neck Squamous Cell Carcinoma Patients Research Articles

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

Background and purposeTumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population.Material and methodsSixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses.ResultsWhile there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels.ConclusionLAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.

Sarcopenia as a Prognostic Marker in Elderly Head and Neck Squamous Cell Carcinoma Patients Undergoing (Chemo-)Radiation.

Sarcopenia is associated with reduced survival and increased toxicity in malignant diseases. The prevalence of sarcopenia increases with age and is an important cause of functional decline. We analyzed sarcopenia and sarcopenia dynamics in elderly head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiation. Skeletal muscle mass of 280 elderly HNSCC-patients (&gt;65 yrs) receiving curative (chemo)radiation was manually outlined and quantified on CT scans at the level of the C3 (C3MA). Cross-sectional muscle area at L3 (L3MA) was calculated and normalized to height (L3MI). Frequency distributions of clinical parameters as well as overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were calculated regarding sarcopenia. Calculated L3MA correlated with pretherapeutic hemoglobin-levels (ρ = 0.280) bodyweight (ρ = 0.702) and inversely with patient-age (ρ = -0.290). Sarcopenic patients featured larger tumors (T3/4 69.0% vs. 52.8%, p &lt; 0.001), a higher burden of comorbidity (age-adjusted Charlson Comorbidity Index 4.8 vs. 4.2, p = 0.015) and more severe chronic toxicities (CTCAE grade 3/4 24.0% vs. 11.8%, p = 0.022). OS was significantly deteriorated in sarcopenic patients with a median of 23 vs. 91 months (logrank p = 0.002) (HR 1.79, CI 1.22-2.60, p = 0.003) and sarcopenia remained an independent prognostic factor for reduced OS in the multivariate analysis (HR 1.64, CI 1.07-2.52, p = 0.023). After therapy, 33% of previously non-sarcopenic patients developed sarcopenia, while 97% of pre-treatment sarcopenic remained sarcopenic. Median bodyweight decreased by 6.8%, whereas median calculated L3MA decreased by 2.4%. In contrast to pretherapeutic, post-therapeutic sarcopenia is no prognosticator for reduced OS. Pretherapeutic sarcopenia is a significant prognostic factor in elderly HNSCC patients undergoing (chemo-)radiation and should be considered in pretherapeutic decision-making. Its role as a predictive marker for tailored supportive interventions merits further prospective evaluation.

Radiotherapy Versus Chemoradiation in Elderly Head-and-Neck Squamous Cell Carcinoma Patients – A Retrospective International Multicenter Study

<h3>Purpose/Objective(s)</h3> While the proportion of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing, the evidence regarding the ideal treatment for this patient cohort is limited. The benefit of concomitant chemotherapy (CT) has been reported to decrease in elderly HNSCC patients; however, it remains unknown whether modern supportive treatments, state-of-the art radiotherapy (RT) techniques and the generally improved performance status of elderly patients nowadays may have altered this observation. <h3>Materials/Methods</h3> Elderly (≥65 years) patients with locoregionally advanced HNSCCs of the oral cavity, oropharynx, hypopharynx or larynx (cT3-4 and/or cN+) receiving definitive RT, with or without concomitant CT, between 2005 and 2019 were eligible for this analysis. Exclusion criteria were recurrent HNSCCs, distant metastases at the time of RT, or HNSCCs from the nasopharynx, salivary glands or the skin. <h3>Results</h3> A total of 824 elderly HNSCC patients from nine tertiary cancer centers met the inclusion criteria and were analyzed. The median age amounted to 72 years (range 65-96 years), and 568 patients (80% of the patients with known ECOG status, n=708) exhibited an ECOG performance status of 0 or 1. The median age-adjusted Charlson Comorbidity Index (CCI) ranged at 4 points (IQR 3-5). Only a minority of HNSCCs (n=140, 17%) exhibited p16 positivity. About half of the cohort suffered from oropharyngeal carcinomas (n=418, 51%), followed by cancers of the hypopharynx (n=151, 18%), oral cavity (n=124, 15%), larynx (n=102, 12%) and multi-level carcinomas (n=29, 4%). A positive smoking history was present in 473 patients (70% of the patients with known smoking status, n=674). Seven hundred thirty-six (89%) of the analyzed patients completed the pre-specified RT dose. OS/PFS amounted to 71%/56% at 1 year, 56%/45% at 2 years, and 46%/38% at 3 years, respectively. Chemoradiation (CRT) resulted in significantly improved OS (HR=0.49, <i>p</i><0.05) and PFS (HR=0.53, <i>p</i><0.05) compared to RT. Even for patients aged ≥75 years (n=329), CRT was associated with superior OS (HR=0.57, <i>p</i><0.05) and PFS (HR=0.61, <i>p</i><0.05). However, patients receiving concomitant CT were significantly younger (<i>p</i><0.05), exhibited a better ECOG performance status (<i>p</i><0.05) and fewer comorbidities (<i>p</i><0.05). In order to control for these disparities, a matched-pair analysis with the matching variables ECOG, CCI and age was conducted, resulting in 98 matching pairs (n=196): Here, both OS (HR=0.44, <i>p</i><0.05) and PFS (HR=0.45, <i>p</i><0.05) remained superior in the CRT compared to the RT group. <h3>Conclusion</h3> This analysis suggests a benefit of concomitant CT in elderly HNSCC patients receiving RT and does not support the usage of a strict age cut-off for CT. Structured assessment of patient performance and comorbidities may help to guide treatment decisions regarding CRT in elderly HNSCC patients.

Elderly Patients with Head-and-Neck Squamous Cell Carcinoma: A Comparison between Surgery and Primary (Chemo)radiation

<h3>Purpose/Objective(s)</h3> Given the higher frequency of comorbidities and frailty, the optimal management of elderly patients with head-and-neck squamous cell carcinoma (HNSCC) is challenging. As randomized trials comparing surgery versus primary (C)RT for this patient population are difficult to perform, we aimed to compare the oncological outcomes between upfront surgery and definitive (C)RT within a large tertiary cancer center. <h3>Materials/Methods</h3> Elderly HNSCC patients (≥65 years) without distant metastases treated with upfront surgery or definitive (C)RT between 2010 and 2020 at a tertiary treatment center were included. Patient characteristics and tumor parameters were compared between both treatment groups using t-tests, Fisher's exact tests and chi-square tests. Overall survival (OS) and progression-free survival (PFS) were calculated, and Cox proportional hazard regression analyses of patient- und tumor-related variables were performed to assess the influence of the choice of primary treatment on survival. <h3>Results</h3> A total of 430 elderly HNSCC patients with a median age of 72 years met the inclusion criteria and were analyzed. Two hundred and seventy-six patients (64.2%) were treated with upfront surgery and risk-adapted adjuvant treatment, and 154 (35.8%) underwent primary (C)RT. Of the 276 patients treated with upfront surgery, 102 patients (37.0%) received adjuvant (C)RT, whereas 174 (63.0%) did not. Incomplete resection occurred in 11 cases (4.0% of the surgery group), while extracapsular spread was present in 33 patients (12.0%). Thirty-five patients (12.7% of the surgery group) received postoperative CRT. Patients receiving primary (C)RT exhibited a worse performance status, were more often smokers and had more often locoregionally advanced tumors (all <i>p</i><0.001). OS and PFS were superior in patients receiving surgery compared to patients treated by (C)RT (OS: HR=2.696, 95% CI 1.976-3.678, <i>p</i><0.001, PFS: HR=2.249, 95% CI 1.664-3.040, <i>p</i><0.001). Age, performance status, comorbidity burden, smoking status, T and N stage and HPV status were prognosticators for OS in the univariate analysis. In the multivariate analysis, choice of primary treatment (OS: HR=1.194, 95% CI 0.563-2.533, <i>p</i>=0.645, PFS: HR=1.112, 95% CI 0.564-2.194, <i>p</i>=0.760) did not constitute a significant parameter for OS or PFS. By restricting analysis to locoregionally advanced tumors (UICC=3-4, n=276), adjuvant (C)RT significantly improved OS compared to surgery alone (median OS: 68 vs. 97 vs. 103 months for surgery vs. surgery+adjuvant RT vs. surgery +postoperative CRT, respectively, <i>p</i><0.05 for surgery vs. surgery+adjuvant RT, <i>p</i>=0.07 for surgery+postoperative CRT). <h3>Conclusion</h3> In the multivariate analysis, upfront surgery with risk-adapted adjuvant treatment and primary (C)RT were comparable treatment approaches for elderly HNSCC patients in terms of oncological outcomes. Therefore, elderly HNSCC patients should be informed about both treatment options in order to ensure informed consent.

PEP503 (NBTXR3), a radioenhancer, in combination with concurrent chemoradiation (CCRT) in locally advanced or recurrent head and neck squamous cell carcinoma (HNSCC): Dose-finding of a phase 1b/2 trial.

e18041 Background: PEP503 (aka NBTXR3), a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is designed for intratumoral injection to increase radiation energy deposition within solid tumors and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test the feasibility and the recommended phase 2 dose (RP2D) of PEP503 intratumoral injection when added with low-dose (LD) weekly cisplatin-containing chemoradiation (CCRT) in HNSCC. Methods: Patients who had T3-4 locally advanced HNSCC suitable for CCRT were eligible. An intratumoral single injection of PEP503 was performed 24 to 72 hours before the start of CCRT: consisting of IMRT (70̃72 Gy, 2-2.12 Gy/fraction) and weekly cisplatin (low dose, 40 mg/m2) concurrently during IMRT. Traditional 3+3 design was planned for dose escalation and 5 levels of PEP503 were planned, including 5%, 10%, 15%, 22%, and 33% of the baseline GTV by MRI. PEP503 Intra-tumor dispersion was anayzed by CT-scan. Results: Twelve (12) patients (male/female: 11/1; oral cavity/oropharynx: 11/1) were enrolled, with 3, 6, and 3 patients at 5%, 10%, and 15% PEP503 dose levels, respectively, in combination with LD cisplatin CCRT. DLTs were observed in one patient at 10% dose level which were G3 ALT and G3 AST increased. Common G3 AEs observed across dose levels were stomatitis (50.0%), WBC decreased (33.3%), decreased appetite (16.7%), neutrophil count decreased (16.7%), and leukopenia (16.7%), and only one G4 AE (hyponatraemia) was observed. CT images demonstrated PEP503 within the tumor contour after injection throughout the CCRT period. Hafnium, for all patients, was either not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 intratumoral injection, and not found in urine. DCR was achieved in 100% of patients with responding patients for an ORR of 58.3%. No subjects received salvage surgery after study treatment. Study was terminated early before MTD and RP2D could be determined. Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for patients with locally advanced or recurrent LA-HNSCC. RP2D was not reached due to study early termination. Clinical trial information: NCT02901483.

Feasibility and quality of life of postoperative concurrent radiotherapy and toripalimab in elderly patients with head and neck squamous cell carcinoma (IMPORT trial).

6066 Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. Aimed to seek out a feasible regimen for concurrent treatment, we evaluated the feasibility and quality of life of postoperative concurrent radiotherapy and toripalimab (anti-PD-1 antibody) in elderly HNSCC patients. Methods: The IMPORT trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at 3 hospitals in China. We randomly assigned (1:1) patients aged＞65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). Following stratification by PS(0-1 vs 2) and pathological adverse features (extranodal extension or positive margin vs others), patients were randomly assigned using a computer-generated randomization list. Acute toxicities were reported. Quality of life were evaluated by EORTC QLQ-C30 and QLQ-H&amp;N35 at baseline, week3, week6 and 1 month after radiotherapy, and the standard scores were compared between groups by linear mixed-effects models. Results: Between September 2020 and December 2021, 38 patients randomly assigned(19 per group). The median age were 70 years (range 66-81) for the RT+PD-1 group and 73 years (range 67-78 years) for RT group. 16 (84.2%) patients in the RT+PD-1 group and 15 (78.9%) patients in the RT group complete the planed radiation dose. In the RT+PD-1 group, 13 (68.4%) patients completed 3 cycles of toripalimab, 3 (15.8%) patients completed 2 cycles due to adverse events and 3 (15.8%) patients declined toripalimab; The most common adverse events of grade 3-5 was oral mucositis (55.6% vs 58.8%) and lymphocyte count decreased(61.1% and 41.2%) in RT+PD-1 group and RT group. In the RT+PD-1 group, only 1 patients experienced grade 3 immune-related enteritis. As to the quality of life scores evaluated by QLQ-C30, no difference was found in standard score of global health status, as well as in most functional scales including: physical, emotion, cognitive and social, except for role functioning (p = 0.045). As to the symptom scale scores evaluated by QLQ-H&amp;N35, no difference was found in standard score of pain, swallowing, dry mouth, opening mouth, and stick saliva, except for speech problem (p = 0.032). Conclusions: For elderly patients with locally advanced HNSCC, postoperative concurrent radiotherapy and toripalimab was safe and feasible. Concurrent toripalimab did not worsen quality of life scores in the majority of cases. Clinical trial information: NCT04523883.

Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients.

Simple SummaryThe aim of this study was to find predictors for adherence to a therapy recommended by a multidisciplinary tumour board regarding 1125 elderly patients (70–100 years) with head and neck squamous cell carcinoma (HNSCC). The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). Nonadherent patients were significantly more often smokers, drinkers, and had a worse tumour stage and lower health status (Karnofsky performance status). In contrast to the chronological patient age, the biological age (Charlson Comorbidity Index) was a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004–2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥ 6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Age-specific oncogenic pathways in head and neck squamous cell carcinoma-are elderly a different subcategory?

In recent clinical practice, an increasing number of elderly patients suffering from head and neck squamous cell carcinoma (HNSCC) of unknown pathophysiology is observed. The majority of HNSCC patients can roughly be divided into three subcategories. First, a small group of young patients who present with variants of genomic aberrations and inheritable diseases like Fanconi anaemia. Second, an increasing population of HPV-related HNSCCs that are regarded as genomic stable tumours with a more favourable prognosis. Though HPV-related tumours used to be more common among younger males, a notable rise in the elderly population is observed. The third subcategory, that of HPV-negative tumours, has been shown to be more heterogeneous with involvement of a variety of oncogenic pathways related to lifestyle factors like smoking and alcohol consumption, often seen in middle-aged males. Some of these pathways could be related to age, such as TP53 alterations, EGFR activation, apoptotic pathway alterations and field cancerization. In this narrative review, we provide an overview of established and newly discovered age-specific pathophysiological mechanisms underlying HNSCC. We propose a fourth subcategory of patients with a suspected different pathophysiology: elderly (HPV-negative) HNSCC patients without a history of tobacco and alcohol consumption. In this subcategory, carcinogenesis seems to be a multi-step process based on genomic instability, immunosenescence, cell cycle disruption and telomere shortening. To conclude, we discuss suggestions for future research to fill the knowledge gap about age-dependent HNSCC carcinogenesis.

Patterns-of-Care Analysis for Radiotherapy of Elderly Head-and-Neck Cancer Patients: A Trinational Survey in Germany, Austria and Switzerland.

ObjectivesThe number of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing, and clinical trials defining the standard of care either excluded or underrepresented elderly patients. This leaves physicians with a challenging and highly individual treatment decision largely lacking clinical evidence.MethodsA tri-national patterns-of-care survey was sent to all members of the German (DEGRO), Austrian (ÖGRO), and Swiss (SRO/SSRO) national societies of radiation oncology. The online questionnaire consisted of 27 questions on the treatment of elderly HNSCC patients, including 6 case-based questions. Frequency distributions and subgroup comparisons were calculated using SPSS statistics software.ResultsA total of 132 answers were collected, including 46(35%) form universities, 52(39%) from non-university-hospitals and 34(26%) from private practices. 83(63%) treat 1-5 and 42(32%) >5 elderly HNSCC patients per month. Target volumes are defined analog current guidelines by 65(50%) of responders and altered based on age/comorbidities or tumor stage by 36(28%) and 28(22%), respectively. Chemotherapy is routinely administered by 108(84%) if indicated, with weekly 40mg/m2 of cisplatin being the favored regimen by 68(53%) in the definitive situation and 60(47%) in the adjuvant setting. Hypofractionation and hyperfractionation/acceleration are used by 26(20%) and 11(9%), respectively. Only 7(5%) clinicians routinely recommend inpatient treatment for elderly HNSCC patients. In a typical definitive patient case, 73(63%) responders recommended chemoradiation with bilateral elective node irradiation analog current guidelines. In an adjuvant example case recommendations regarding elective volume and chemotherapy were heterogeneous. Differences between responders’ institutions concern the frequency of PET-CT in staging, preventive port-catheter and PEG implantation, the choice of chemotherapy regimens and the use of alternative fractionations.ConclusionTreatment of elderly HNSCC-patients in the German-speaking countries mainly follows guidelines established for younger patients. Algorithms for patient stratification and treatment de-escalation for “unfit” elderly patients are needed.

Development and External Validation of a Prognostic Classifier for Elderly Head-and-Neck Cancer Patients Undergoing (Chemo)radiation

Elderly head-and-neck squamous cell carcinoma (HNSCC) patients form a heterogeneous cohort, and survival estimation is often challenging due to underlying comorbidities. Prognostic classifiers and nomograms may therefore be useful for overall survival (OS) estimation in order to provide shared decision-making in the clinical routine.A total of 284 elderly HNSCC patients aged ≥65 years who received a curative (chemo)radiation between 2010 and 2020 at a tertiary cancer center were used for the development of a survival classifier. On the basis of a multivariate Cox regression analysis, significant parameters were identified for which points were given according to the beta regression values. The derived classifier was then validated in a second, external cohort consisting of 217 elderly HNSCC patients undergoing (chemo)radiation. Based on the cumulative data of 501 patients, a nomogram for the 2-year and 4-year OS was created. We then examined in a third independent cohort whether the classifier could also stratify the prognosis of surgically treated elderly HNSCC patients without adjuvant (chemo)radiation (n = 169).In the multivariate backward stepwise Cox regression with likelihood ratio tests using P < 0.1 as inclusion criterion, the Karnofsky Performance Status (KPS, HR = 2.654, P < 0.001), the age-adjusted Charlson Comorbidity Index (CCI, HR = 2.598, P < 0.001) and the pre-radiotherapy CRP serum concentration (HR = 1.634, P = 0.064) were significant prognostic parameters for OS. Following the beta regression values, a KPS ≤70% and a CCI ≥6 points were given 1 point, while a CRP concentration ≥5 mg/L was given 0.5 points. The median OS was 107 (0 points), 34 (0.5 points), 28 (1 point), 11 (1.5 points), 9 (2 points) and 6 months (2.5 points), respectively. In order to obtain considerably distinct prognostic subgroups, 3 prognostic groups were created: A favorable (0 points), an intermediate (0.5-2 points) and a poor (2.5 points) subgroup. While the median OS for the favorable group amounted to 107 months, it was 28 and 6 months for the intermediate and poor cohorts, respectively (P < 0.001, log-rank test). In the external cohort, the median OS was found to range at 130, 29 and 9 months for the favorable, intermediate and poor group, respectively (P = 0.005). Using the aggregated data of both cohorts, a nomogram based on the KPS, CCI and CRP was created for the 2-year and 4-year OS that exhibited a concordance index of 0.65 (Harrell's C). For the surgically treated cohort of elderly HNSCC patients, only the KPS ≤70% (HR = 5.950, P = 0.002) but not the CCI ≥6 points (HR = 1.937, P = 0.232) or the baseline CRP serum value (HR = 1.743, P = 0.328) were significant prognosticators.We developed and externally validated a clinically feasible survival score for elderly HNSCC patients undergoing (chemo)radiation. Both the score and nomogram may be useful aiding shared decision-making of radiation oncologists and medical oncologists treating elderly HNSCC patients.

FACTORS INFLUENCING TREATMENT OUTCOME OF NON-NASOPHARYNGEAL HEAD AND NECK SQUAMOUS CELL CARCINOMA IN GERIATRIC PATIENTS

Background: Head and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of malignancy. Their incidenceincreases with age. Therefore, elderly HNSCC patients represent a large population who need special care and treatment considerations.Aim of work:To correlate clinicopathologic factors of non-nasopharyngeal HNSCC geriatric patients with disease free survival (DFS) and overall survival (OS).Patients and methods:A retrospective analysis of fifty non-nasopharyngeal HNSCC elderly patients (≥ 65 years) treated at the head and neck cancer unit at the clinical oncology department, Ain Shams University Hospitals from June 2014 to June 2019. The study correlatedpatients’ age, comorbidities, tumor stage and Eastern Cooperative Oncology Group performance state (ECOG PS) with disease free survival (DFS) and overall survival (OS).Results:Three years DFS rate among the patients aged 65-75 years was 73% versus 40% among patients aged 76-80 years and three years OS rate decreased from 48.2% to 40% respectively. The median OS was 39.5 months for patients without co-morbidities compared to 32.5 months for patients with associated co-morbidities (P=0.9) and the median DFS was nearly about 40 months for both groups (p=0.7).Three years DFS was 78.7% among the patients with PS I and 54% among PS II and III (P=0.56) while three years OS rate was 60.7% among patients with PS I but it was 42% for PS II and III (p=0.5). The mean DFS dropped from 43.9 months to 18.4 months for early stages and locally advanced respectively but with no statistical significance association (P=0.49). There was marked decrease of 2years OS from 100% for early stages to 40.3% for locally advanced stages (p=0.009).Conclusion: In HNSCC geriatric patients age >75 years and locally advanced stages were poor prognostic factors for DFS and OS while co-morbidities and ECOG PS didn’t affect treatment outcome.

Development and validation of a novel prognostic score for elderly head-and-neck cancer patients undergoing radiotherapy or chemoradiation

Background and purposeTo establish a clinically feasible prognostic score and nomogram based on easily accessible clinical data that will aid decision-making in elderly head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. Material and methods284 elderly HNSCC patients (≥65 years) undergoing curative (chemo)radiotherapy were included for the development of a score predicting overall survival (OS) based on the beta regression coefficients from significant parameters in a multivariate Cox regression analysis with p < 0.1 as inclusion criterion. A second, external cohort of 217 elderly HNSCC patients receiving (chemo)radiotherapy was used for validation. Using the aggregated data (n = 501), a nomogram was developed to predict 2- and 4-year OS. ResultsKarnofsky Performance Status (HR = 2.654; p < 0.001), Charlson Comorbidity Index (HR = 2.598; p < 0.001) and baseline C-reactive protein (CRP) level (HR = 1.634; p = 0.068) were prognostic for OS in the multivariate analysis. An OS score based on beta regression coefficients was created, in which reduced performance status, increased comorbidity burden and increased CRP levels were included, leading to 3 distinct survival groups. The median OS for the 3 groups amounted to 107, 28 and 6 months, respectively (p < 0.001). The developed score was able to significantly differentiate between a favorable (median OS = 130 months), intermediate (29 months) and unfavorable prognosis (9 months) also in the external validation cohort (p = 0.005). ConclusionWe propose a novel, validated prognostic score based on easily accessible clinical data allowing stratification between prognostic groups of elderly HNSCC patients receiving (chemo)radiotherapy. The derived nomogram for the prediction of 2-year and 4-year OS may aid decision-making for this vulnerable population.

The Value of Laboratory Parameters for Anemia, Renal Function, Systemic Inflammation and Nutritional Status as Predictors for Outcome in Elderly Patients with Head-and-Neck Cancers.

The purpose of this study was to evaluate the value of routine blood markers regarding their predictive potential for treatment outcomes of elderly head-and-neck squamous cell carcinoma (HNSCC) patients. In total, 246 elderly HNSCC patients (≥65 years) undergoing (chemo)radiotherapy from 2010 to 2018 were analyzed for treatment outcomes, depending on their hemoglobin, glomerular filtration rate (GFR), C-reactive protein (CRP) and albumin values, representing anemia, kidney function, inflammation and nutrition status, respectively. Local/locoregional control, progression-free and overall survival (OS) were calculated using the Kaplan–Meier method. Cox analyses were performed to examine the influence of blood parameters on oncological outcomes. In the univariate Cox regression analysis, hemoglobin ≤ 12 g/dL (HR = 1.536, p < 0.05), a GFR ≤ 60 mL/min/1.73 m2 (HR = 1.537, p < 0.05), a CRP concentration > 5 mg/L (HR = 1.991, p < 0.001) and albumin levels ≤ 4.2 g/dL (HR = 2.916, p < 0.001) were significant risk factors for OS. In the multivariate analysis including clinical risk factors, only performance status (HR = 2.460, p < 0.05) and baseline albumin (HR = 2.305, p < 0.05) remained significant prognosticators. Additionally, baseline anemia correlated with the prevalence of higher-grade chronic toxicities. We could show for the first time that laboratory parameters for anemia (and at least partly, tumor oxygenation), decreased renal function, inflammation and reduced nutrition status are associated with impaired survival in elderly HNSCC patients undergoing (chemo)radiotherapy.

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

IntroductionThe number of aging cancer patients has increased continuously and will do so further in the future. The immune system of elderly people experiences critical changes over the time. Therefore, tumor-induced changes in the immune system are believed to differ in young and elderly cancer patients as well.MethodsThe effect of aging on the immune system was measured in peripheral blood lymphocytes (PBL) of healthy volunteers (n = 48, 21–84 yrs.) divided into three different age groups. Seventy years was set as a cut-off for defining subjects as elderly. Results were compared to two groups of adult cancer patients, which donated PBL and tumor infiltrating lymphocytes (TIL): young cancer patients (40–69 yrs.; blood: n = 13; TIL: n = 17) and elderly cancer patients (70–90 yrs.; blood: n = 20; TIL: n = 15) with head and neck squamous cell carcinoma (HNSCC). Frequencies and phenotypes of CD4+ and CD8+ T cells as well as regulatory T cells (Treg) were assessed by flow cytometry.ResultsWe observed lower frequencies of CD8+ cytotoxic T cells during aging in both groups. Frequencies of tumor infiltrating regulatory T cells were significantly higher than in the peripheral blood but showed a significant decline in older tumor patients. With increasing age, expression of immunosuppressive CD73 and CCR7 was lower and expression of PD1 elevated on peripheral T cells in healthy volunteers and tumor patients.ConclusionImmunosenescence takes place in healthy donors and cancer patients. Our results suggest that in elderly tumor patients, the immune system is impaired and the tumor-induced immune escape is less pronounced. The increased expression of PD1 implies the potential for effective immunotherapies in elderly, as treatment with checkpoint inhibitors could be more beneficial for elderly HNSCC patients.

Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer

ObjectivesSarcopenia is known as a geriatric syndrome associated with increased disability and decreased survival in elderly patients. In oncological patients, pretreatment low skeletal muscle mass (SMM), sometimes referred to as sarcopenia, is an emerging negative prognostic factor. Commonly, only SMM is assessed in cancer patients. Sarcopenia is defined as the combination of low SMM and low muscle function (MF). We investigated the relation between SMM, MF, sarcopenia (SMM and MF combined), and overall survival (OS) in a group of elderly patients with head-and-neck squamous cell carcinoma (HNSCC).Patients and methodsA retrospective study in elderly HNSCC patients treated between 2015 and 2018 was performed. The prognostic value of SMM and MF seperately, and sarcopenia was investigated.ResultsEighty-five patients were included of whom 48.2% had sarcopenia. The median OS was significantly worse for patients treated with curative intent with sarcopenia (12.07 months; IQR 3.64–21.82) compared to patients without sarcopenia (13.60 months; IQR 5.98-27.00) (HR 2.80; 95% CI 1.14–6.88; p = 0.03). SMM and MF seperately were not significant predictors of OS.ConclusionSarcopenia is associated with impaired OS in elderly HNSCC patients. Sarcopenia, defined as the combination of low SMM and low MF, appears to be a better predictor of OS than low SMM or low MF separately.

Demographic predictors of head and neck cancer survival differ in the elderly.

Head and neck squamous cell carcinoma (HNSCC) prognosis strongly correlates with demographic factors. This study aimed to determine whether demographic predictors of HNSCC survival differ between age cohorts, with an emphasis on the growing elderly demographic. Outcomes research. Adults with squamous cell carcinoma of the upper aerodigestive tract were identified from the Surveillance, Epidemiology and End Results 18 database. Demographic and oncologic factors were compared between three age groups: 18 to 49, 50 to 74, and >75 years. Factors associated with cancer-specific survival were assessed in each cohort using subdistribution hazard ratio (sHR) and 95% confidence interval (CI) produced by multivariate competing risk models. A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882 (14.3%) less than 50 years old. Older patients were more often female (35.4% vs. 25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and 75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and 51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%). In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95% CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated with lower mortality in all age groups but with diminishing effects (single sHR: young 1.52, middle 1.31, older 1.14). Elderly HNSCC patients have distinct effects from demographic prognostic factors and should be considered a separate subgroup with unique epidemiology, risks, and preferences. 2c Laryngoscope, , 129:146-153, 2018.

Survival Patterns in Elderly Head and Neck Squamous Cell Carcinoma Patients Treated With Definitive Radiation Therapy

We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), and non-cancer-related death (NCRD) in elderly (aged ≥70years) head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiation therapy. The results were compared with those of younger patients, and the most important prognostic factors for survival endpoints were determined. Treatments may be better justified based on identification of the main differences in survival between young and elderly patients. Data were analyzed from all consecutive HNSCC patients treated with definitive radiation therapy (66-70Gy) in our department between April 2007 and December 2014. A total of 674 patients, including 168 elderly patients (24.9%), were included in the study. Multivariate association models were constructed to assess the effect of age on survival endpoints. Multivariate analysis was performed to identify potential prognostic factors for survival in elderly patients. A total of 674 consecutive patients, including 168 elderly patients, were analyzed. The 5-year OS and NCRD rates were significantly worse for elderly patients than for young patients: 45.5% versus 58.2% (P=.007) and 39.0% versus 20.7% (P<.001), respectively. In the multivariate association analysis on the relationship between age and OS, lymph node involvement and worse World Health Organization (WHO) performance status were identified as significant confounders. Multivariate association analysis between age and NCRD identified Union for International Cancer Control stage as a significant confounder. After correction for confounders, the effect of age on OS and NCRD increased. Worse WHO performance status, lymph node involvement, and specific tumor site were independent prognostic factors for OS and CSS in the elderly patient group. Of the elderly patients, 80 (47%) died during follow-up; 45% of these deaths were ascribed to the index tumor.For elderly patients, radiation therapy combined with systemic forms of treatment was significantly associated with adverse NCRD rate (hazard ratio, 8.02; 95% confidence interval, 2.36-27.2; P=.001) after we performed a multivariate association analysis. Elderly HNSCC patients have worse survival outcomes than young HNSCC patients. Age is an independent prognostic factor for OS, mainly due to an increase in non-cancer-related mortality and comorbid diseases. The differences in CSS between young and elderly patients are negligible.

Patterns of care in elderly patients with squamous cell carcinoma of the head and neck: A SEER-Medicare analysis.

5539 Background: Head and neck squamous cell carcinoma (HNSCC) is predominantly a disease of the elderly, however age and co-morbidity may affect therapy decisions. The purpose of this study was to assess the patterns of care of elderly HNSCC patients and identify factors associated with non-receipt of surgery and chemoradiation (CRT). Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007) we identified a retrospective cohort of non-metastatic HNSCC patients and categorized them into treatment cohorts. Comparisons were made between surgery vs. non-surgery, and CRT vs. non-CRT cohorts. Multivariate logistic regression models examined factors associated with non-receipt of treatment. Variables included tumor location, stage, year of diagnosis, age, gender, marital status, race, comorbidity, race-comorbidity interaction, SEER region, socioeconomic variables, and hospital affiliations. Results: The final cohort of 11,336 were 63% male and 83% white. 52% had no co-morbidities, 44% had oral cavity HNSCC, 52% were diagnosed between 2002 and 2007, 58% had surgery, and 21% received CRT. For the CRT vs. non-CRT model, increasing age (OR = 0.93; 95% CI 0.92 -0.94) and non-whites with co-morbidity (OR = 0.71; 95% CI 0.55 – 0.92) were associated with decreased likelihood of receiving CRT. More advanced staged disease, oropharyngeal tumor location, and diagnosis after 2002 were associated with increased likelihood of receiving CRT. For the surgery versus non-surgery model, age was not associated with receipt of surgery (OR 0.99; 95% CI 0.99-1.00), nor was existence of comorbidity in white patients (OR 0.97; 95% CI 0.88-1.05). However, recent year of diagnosis, non-oral cavity tumor location, and advanced stage were all associated with reduced likelihood of receiving surgery. During the 15 year surveillance period, patients were less likely to receive surgery, and CRT was used more often. Conclusions: Age may influence the non-receipt of CRT in this elderly cohort but does not appear to be significantly associated with the non-receipt of surgery. There has been an increasing trend in the receipt of CRT with a decrease in surgery over the past 15 years.