Geriatric assessment and quality of life for 2 years in older patients with head and neck cancer.

Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC.EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer's (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months.In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score.There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. TRIAL REGISTRATION: NCT02025062.

[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

Effectiveness of Geriatric Assessment-Driven Interventions on Survival and Functional and Nutritional Status in Older Patients with Head and Neck Cancer: A Randomized Controlled Trial (EGeSOR).

This study assesses the efficacy of Geriatric Assessment (GA)-driven interventions and follow-up on six-month mortality, functional, and nutritional status in older patients with head and neck cancer (HNC). HNC patients aged 65 years or over were included between November 2013 and September 2018 by 15 Ear, Nose, and Throat (ENT) and maxillofacial surgery departments at 13 centers in France. The study was of an open-label, multicenter, randomized, controlled, and parallel-group design, with independent outcome assessments. The patients were randomized 1:1 to benefit from GA-driven interventions and follow-up versus standard of care. The interventions consisted in a pre-therapeutic GA, a standardized geriatric intervention, and follow-up, tailored to the cancer-treatment plan for 24 months. The primary outcome was a composite criterion including six-month mortality, functional impairment (fall in the Activities of Daily Living (ADL) score ≥2), and weight loss ≥10%. Among the patients included (n = 499), 475 were randomized to the experimental (n = 238) or control arm (n = 237). The median age was 75.3 years [70.4-81.9]; 69.5% were men, and the principal tumor site was oral cavity (43.9%). There were no statistically significant differences regarding the primary endpoint (n = 98 events; 41.0% in the experimental arm versus 90 (38.0%); p = 0.53), or for each criterion (i.e., death (31 (13%) versus 27 (11.4%); p = 0.48), weight loss of ≥10% (69 (29%) versus 65 (27.4%); p = 0.73) and fall in ADL score ≥2 (9 (3.8%) versus 13 (5.5%); p = 0.35)). In older patients with HNC, GA-driven interventions and follow-up failed to improve six-month overall survival, functional, and nutritional status.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

Tracheostomy in COVID-19 acute respiratory distress syndrome patients and follow-up: A parisian bicentric retrospective cohort.

BACKGROUND: Tracheostomy has been proposed as an option to help organize the healthcare system to face the unprecedented number of patients hospitalized for a COVID-19-related acute respiratory distress syndrome (ARDS) in intensive care units (ICU). It is, however, considered a particularly high-risk procedure for contamination. This paper aims to provide our experience in performing tracheostomies on COVID-19 critically ill patients during the pandemic and its long-term local complications. METHODS: We performed a retrospective analysis of prospectively collected data of patients tracheostomized for a COVID-19-related ARDS in two university hospitals in the Paris region between January 27th (date of first COVID-19 admission) and May 18th, 2020 (date of last tracheostomy performed). We focused on tracheostomy technique (percutaneous versus surgical), timing (early versus late) and late complications. RESULTS: Forty-eight tracheostomies were performed with an equal division between surgical and percutaneous techniques. There was no difference in patients' characteristics between surgical and percutaneous groups. Tracheostomy was performed after a median of 17 [12-22] days of mechanical ventilation (MV), with 10 patients in the "early" group (≤ day 10) and 38 patients in the "late" group (> day 10). Survivors required MV for a median of 32 [22-41] days and were ultimately decannulated with a median of 21 [15-34] days spent on cannula. Patients in the early group had shorter ICU and hospital stays (respectively 15 [12-19] versus 35 [25-47] days; p = 0.002, and 21 [16-28] versus 54 [35-72] days; p = 0.002) and spent less time on MV (respectively 17 [14-20] and 35 [27-43] days; p<0.001). Interestingly, patients in the percutaneous group had shorter hospital and rehabilitation center stays (respectively 44 [34-81] versus 92 [61-118] days; p = 0.012, and 24 [11-38] versus 45 [22-71] days; p = 0.045). Of the 30 (67%) patients examined by a head and neck surgeon, 17 (57%) had complications with unilateral laryngeal palsy (n = 5) being the most prevalent. CONCLUSIONS: Tracheostomy seems to be a safe procedure that could help ICU organization by delegating work to a separate team and favoring patient turnover by allowing faster transfer to step-down units. Following guidelines alone was found sufficient to prevent the risk of aerosolization and contamination of healthcare professionals.

Donor site sequelae and patient satisfaction after head and neck reconstruction with a radial forearm free flap.

PURPOSE: Radial forearm free flap (RFFF) being a workhorse flap in head and neck reconstruction, we investigated its donor site delayed consequences. METHODS: Multicentric case series evaluating 189 patients who underwent RFFF for carcinologic reasons at least 6 months before. Patients and surgeon's appreciation regarding the aesthetic and functional consequences of the flap harvest on their daily life were evaluated by questionnaires using likert scales. Medical data were collected from patients' charts retrospectively. RESULTS: Thirty percent of patients had at least one sequelae. Experiencing a graft necrosis did not worsen long-term results. Cosmetic satisfaction was significantly worst for women, according to patients' and surgeons' opinion. For 81% and 92% patients, respectively, the flap harvest had no impact on daily life nor sport practice. Ratio between the benefits of reconstruction and the sequelae at the donor site was judged "excellent" for 77% patients. CONCLUSIONS: Although objectively important, RFFF morbidity has little impact in head and neck cancer patient's life.

Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases.

BACKGROUND: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival. PATIENTS AND METHODS: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015. RESULTS: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis. CONCLUSION: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

[Diagnostic and treatment pitfalls and guidelines for variants of squamous cell carcinomas of the head and neck: on behalf of the REFCOR]. / Variants des carcinomes épidermoïdes dans les voies aérodigestives supérieures (VADS), implications pour le diagnostic et la prise en charge, selon les référentiels du REFCOR.

Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas.

Macrophages in the microenvironment of head and neck cancer: potential targets for cancer therapy.

The microenvironment of solid tumors has become a promising target for future therapies modulating immune cells. Patients with advanced head and neck cancer, which still portends a poor outcome, are particularly in need of innovative approaches. In oral squamous cell carcinoma, high density of tumor-associated macrophages (TAMs) appears consistently associated with poor prognosis, whereas data are currently limited for other head and neck sites. Several approaches to block TAMs have been investigated, including TAMs inactivation by means of the colony stimulating factor 1 (CSF-1)/CSF-1 receptor (CSF-1R) inhibitors or strategies to reprogram TAMs from M2 protumoral phenotype toward M1 antitumoral phenotype. This review focuses on both prognostic and therapeutic aspects related to TAMs in head and neck carcinomas.

[A rare endolaryngeal tumor]. / Une tumeur rare endolaryngée.

We report the case of a 65-year-old woman who presented with a dysphonia. ENT tomography and laryngoscopy showed an endolaryngeal tumoral lesion extended to the right supraglottis. Biopsy of the lesion revealed dense lymphoid infiltrate in the lamina propria, without necrosis or ulceration of the mucosa. The infiltrate showed many CD3+, CD5+, CD4+, CD8+ lymphocytes and plasmocytes. Larger lymphoid cells with cytologic atypia expressed CD56 and cytotoxicity markers such as TIA1 and granzyme B. In situ hybridization for EBV revealed numerous positive cells. The diagnosis of extranodal NK/T cell lymphoma was proposed. The primary laryngeal localization of this disease is exceptionally rare. Heavy admixture of inflammatory cells may mimic inflammatory process and delay the diagnosis.

Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study.

AIMS: To evaluate the impact of human papillomavirus (HPV) status, tobacco smoking and initial treatment approach on progression-free survival (PFS) and overall survival (OS) for oropharyngeal cancer (OPC) in France, a country where smoking declines started late (1990s). METHODS: 340 OPC patients (median age: 60years) from 14 French hospitals were followed up (median 26.7months). PCR-based positivity for both HPV DNA and E6/E7 mRNA was used to distinguish HPV-positive OPC (27.1%). Hospital-stratified hazard ratios (HR) and corresponding 95% confidence intervals (CI) were used to compare PFS and OS according to HPV and other prognostic factors in hospital-stratified unadjusted and multivariate models. The combined effect of HPV status with either smoking, stage, or initial treatment on PFS was also evaluated. RESULTS: PFS in multivariate analysis was better in HPV-positive patients (HR=0.42; 95% CI: 0.24-0.73) and worse in older patients (HR for 5-year age increase=1.12) and those having had firstly radiotherapy (HR=1.86; 95% CI: 1.19-2.92) or induction chemotherapy (HR=1.73; 95% CI: 1.08-2.79) instead of upfront surgery. Findings for OS were similar. Loco-regional recurrences were less frequent in HPV-positive (10.5%) than HPV-negative patients (26.0%) but distant recurrences were similarly frequent. HPV status did not modify the influence of smoking or stage on PFS but the impossibility to perform upfront surgery may be more relevant for HPV-negative patients. CONCLUSIONS: HPV-positive OPC patients fare better than HPV-negative OPC and may benefit from toxicity-sparing. Whether HPV-negative patients responded less well to radiation and chemotherapy because of more severe genomic damage or bulkier tumours is unclear.

Human papilloma virus prevalence in HIV patients with head and neck squamous cell carcinoma.

OBJECTIVE: The implication of human papilloma virus (HPV) in head and neck squamous cell carcinoma (HNSCC) is well established, especially in oropharyngeal SCC. HIV patients have a higher risk of persistent HPV infection. We investigated the role of HPV in HNSCC carcinogenesis in HIV population. DESIGN: Retrospective monocentric study. METHODS: We studied HIV patients who presented with HNSCC between 1994 and 2014. For each patient, tumor characteristics, HIV disease, and survival information were collected. Tumor HPV testing was performed using p16 immunohistochemistry (IHC), in-situ hybridization and PCR. We assessed the percentage of HPV in this population of HIV patients with HNSCC and compared HIV disease characteristics based on HPV status. RESULTS: Forty-seven patients were included: 11 women/36 men, the median age was 50 years. Tumor HPV testing was performed in 40 patients. Tumors were located in oropharynx (32%), oral cavity (32%), larynx (21%), and hypopharynx (11%). At the time of diagnosis, median CD4 level was 385 cells/µl, 31% of the patients were stage (Centers for Disease Control, stage C). The percentage of HPV linked to HNSCC for all locations in HIV patients was 30% (n = 12). HPV16 accounted for 50% of all HPV genotypes. HPV positive status was associated with a CD4 nadir of less than 200 (P = 0.026), but not with CD4 level at time of diagnosis (P = 0.414). HPV-negative tumors tend to be associated with poorer 5-year overall survival (hazard ratio = 2.9, P = 0.0711). CONCLUSION: HPV plays a critical role in HNSCC development in HIV population. HIV immunodeficiency may increase HPV persistence and progression of HNSCC.

Focus on the role of the CXCL12/CXCR4 chemokine axis in head and neck squamous cell carcinoma.

The human chemokine system includes approximately 48 chemokines and 19 chemokine receptors. The CXCL12/CXCR4 system is one of the most frequently studied that is also found overexpressed in a large variety of tumors. The CXCL12/CXCR4 axis has been increasingly identified as an important target in cancer growth, metastasis, relapse, and resistance to therapy. In this review, we highlight current knowledge of the molecular mechanisms involving chemokines CXCL12/CXCR4 and their consequences in head and neck squamous cell carcinoma (HNSCC). Overexpression of CXCL12/CXCR4 in HNSCC appears to activate cellular functions, including motility, invasion, and metastatic processes. Current findings suggest that CXCR4 and epithelial-mesenchymal transition markers are associated with tumor aggressiveness and a poor prognosis, and may be suitable biomarkers for head and neck tumors with high metastatic potential. Furthermore, knowledge of the role of CXCR4 in HNSCC could influence the development of new targeted therapies for treatment, aimed at improving the prognosis of this disease.

PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer.

Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3(+) T cells and programmed death-1 (PD-1)(+) T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1(+) T cells and the levels of PD-1(+) cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade.

Clinical outcome after a totally implantable venous access port-related infection in cancer patients: a prospective study and review of the literature.

Morbidity and mortality after a totally implantable venous access port (TIVAP)-related infection in oncology patients have rarely been studied. We conducted this study to assess the incidence and factors associated with the following outcome endpoints: severe sepsis or septic shock at presentation, cancellation of antineoplastic chemotherapy, and mortality at week 12. We conducted a prospective single-center observational study including all adult patients with solid cancer who experienced a TIVAP-related infection between February 1, 2009, and October 31, 2010. Patients were prospectively followed for 12 weeks. Among 1728 patients receiving antineoplastic chemotherapy during the inclusion time, 72 had an episode of TIVAP-related infection (4.2%) and were included in the study (median age, 60 yr; range, 28-85 yr). The incidence of complications was 18% for severe sepsis or septic shock (13/72 patients), 30% for definitive cancellation of antineoplastic chemotherapy (14/46 patients who still had active treatment), and 46% for death at week 12 (33/72 patients). Factors associated with severe sepsis or septic shock were an elevated C-reactive protein (CRP) level and an infection caused by Candida species; 4 of the 13 severe episodes (31%) were due to coagulase-negative staphylococci (CoNS). Factors associated with death at week 12 were a low median Karnofsky score, an elevated Charlson comorbidity index, the metastatic evolution of cancer, palliative care, and an elevated CRP level at presentation. Hematogenous complications (that is, infective endocarditis, septic thrombophlebitis, septic pulmonary emboli, spondylodiscitis, septic arthritis, or organ abscesses) were found in 8 patients (11%). In conclusion, patients' overall condition (comorbidities and autonomy) and elevated CRP level were associated with an unfavorable clinical outcome after a TIVAP-related infection. Candida species and CoNS were responsible for severe sepsis or septic shock.

Prognostic value of the chemokine receptor CXCR4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue.

OBJECTIVE: The aim of this study was to evaluate the expression and the prognostic value of chemokine receptor 4 (CXCR4), its cognate ligand the CXCL12, and markers of epithelial-to-mesenchymal transition (EMT) in squamous cell carcinoma (SCC) of the mobile tongue. PATIENTS AND METHODS: Patients with primary SCC of the mobile tongue who underwent surgery in our center were screened retrospectively. Patients without prior treatment, who had pre-surgery TNM staging and available tumor samples, were eligible. Protein expression of CXCL12, CXCR4, CA9, E-cadherin, and vimentin was determined by immunohistochemical staining, scored, and correlated with clinical and pathological parameters and overall survival. Multivariate and Cox proportional hazards analyses were performed. RESULTS: Among 160 patients treated and screened, 47 were analyzed. CXCR4 and CXCL12 expression was high in tumor cells. CXCR4 expression in primary tumor samples was significantly higher in patients with high-grade tumors, lymph node metastases, and microscopic nerve invasion (p ≤ 0.05). There was a non-significant trend towards a correlation between high CXCL12 expression and pathologic tumor stage (p=0.07). Tumors with high CXCR4 expression correlated with poor overall survival (hazard ratio=3.6, 95% confidence interval 1.3-9.7; p=0.011), notably in the CXCR4(high)/vimentin-positive subgroup. Vimentin-positive tumors, characterizing EMT, were associated with lower survival (hazard ratio=4.5, 95% confidence interval 1.6-12.3; p=0.0086). Multivariate analysis confirmed vimentin (but not CXCR4) expression as an independent prognostic factor of poor overall survival (p=0.016). CONCLUSION: Our results suggest that CXCR4 is a marker of tumor aggressiveness and vimentin is an important and independent prognostic factor in patients with SCC of the mobile tongue.

The use of harmonic scalpel for free flap dissection in head and neck reconstructive surgery.

Surgeons conventionally use electrocautery dissection and surgical clip appliers to harvest free flaps. The ultrasonic Harmonic Scalpel is a new surgical instrument that provides high-quality dissection and hemostasis and minimizes tissue injury. The aim of this study was to evaluate the effectiveness and advantages of the ultrasonic Harmonic Scalpel compared to conventional surgical instruments in free flap surgery. This prospective study included 20 patients who underwent head and neck reconstructive surgery between March 2009 and May 2010. A forearm free flap was used for reconstruction in 12 patients, and a fibular flap was used in 8 patients. In half of the patients, electrocautery and surgical clips were used for free flap harvesting (the EC group), and in the other half of the patients, ultrasonic dissection was performed using the Harmonic Scalpel (the HS group). The following parameters were significantly lower in the HS group compared to the EC group: the operative time of flap dissection (35% lower in the HS group), blood loss, number of surgical clips and cost of surgical materials. This study demonstrated the effectiveness of the Harmonic Scalpel in forearm and fibular free flap dissections that may be extended to other free flaps.