Outcomes of comprehensive geriatric assessment and surgical management in head and neck cancers of the elderly: an observational study.

AIM: The aims of this study were to assess the survival benefit of optimal vs suboptimal management in elderly patients presenting with upper aerodigestive tract (UADT) cancer for which surgery was the standard of care, and determine if comprehensive geriatric assessment (CGA) was a prognostic factor for survival. MATERIALS AND METHODS: This single-center retrospective cohort study was conducted from January 2014 to December 2018. Included patients were aged 70 or older at the time of diagnosis, and presented with UADT cancer with a theoretical indication for curative-intent surgery according to international guidelines. RESULTS: A total of 188 patients were included, with a median age of 78 years. Treatment included surgery in 67.6% of cases and was considered optimal in 60.6% of patients. The overall 3-year survival was 55.2%, and was significantly better in case of optimal vs suboptimal treatment (74.5% vs 25.8%, p < 0.001). In univariate analysis, factors associated with a significantly improved 3-year survival included surgery (p < 0.001), age < 80 years, performance status < 2 and G8 score > 14. In multivariate analysis, CGA was associated with a better survival. CONCLUSIONS: In patients aged over 70 presenting with UADT cancer for which the standard of care is surgery, an optimal management is associated with better overall survival. Receiving a CGA seems to provide a survival benefit in patients with a G8 score ≤ 14, through an optimization of the care pathway before and after the cancer treatment.

Oncological outcomes and prognostic factors of squamous cell carcinoma of the upper gingiva and hard palate: a retrospective study.

PURPOSE: Despite sharing the same staging system as oral cavity cancers, upper gingiva and hard palate (UGHP) squamous cell carcinoma (SCC) have several features that make them a different entity. We aimed to analyze oncological outcomes and adverse prognostic factors of UGHP SCC, and assess an alternate T classification specific to UGHP SCC. METHODS: Retrospective bicentric study including all patients treated by surgery for a UGHP SCC between 2006 and 2021. RESULTS: We included 123 patients with a median age of 75 years. After a median follow-up of 45 months, the 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 57.3%, 52.7% and 74.7%, respectively. Perineural invasion, tumor size, bone invasion, pT classification and pN classification were statistically associated with poorer OS, DFS and LC on univariate analysis. On multivariable analysis, the following variable were statistically associated with a poorer OS: past history of HN radiotherapy (p = 0.018), age > 70 years (p = 0.005), perineural invasions (p = 0.019) and bone invasion (p = 0.030). Median survivals after isolated local recurrence were 17.7 and 3 months in case of surgical and non-surgical treatment, respectively (p = 0.066). The alternate classification allowed better patient distribution among T-categories, however without improving prognostication. CONCLUSION: There is a broad variety of clinical and pathological factors influencing prognosis of SCC of the UGHP. A comprehensive knowledge of their prognostic factors may pave the way towards a specific and more appropriate classification for these tumors.

Adjuvant brachytherapy for oral squamous cell carcinomas: a single-center experience comparing low-dose and pulsed-dose-rate techniques.

OBJECTIVE: This study aims to assess the outcomes of adjuvant interstitial brachytherapy (BT) to the tumor bed for oral cavity squamous cell carcinoma (SCC), and to compare the oncological outcomes and toxicity profile of low-dose-rate (LDR) and pulsed-dose-rate (PDR) BT. DESIGN: This retrospective single-center study included all patients who underwent postoperative LDR- or PDR-BT to the tumor bed as the sole adjuvant treatment for an oral tongue or floor of the mouth SCC between January 2000 and December 2020. RESULTS: A total of 79 patients were eligible for this study. The cohort was divided into an LDR group (n = 38) and a PDR group (n = 41). The median time interval between surgery and brachytherapy was 55 days. Median delivered total dose was 55 Gy and median hospital stay was 5 days. Five patients (8.3%) experienced grade 3-4 early toxicity, 2 in the LDR group and 3 in the PDR group. Late toxicities were present in 28 patients (44.4%) and were dominated by grade 1-2 residual pain and dysesthesia, without a statistical difference between the groups. After a median follow-up of 65.1 months, 5­year local control (LC), disease-free survival (DFS), and overall survival (OS) for the whole cohort were 76.3% (95% CI = 63.4-85.1), 61.6% (95% CI = 49.0-72.0), and 71.4% (95% CI = 58.6-80.8), respectively. CONCLUSION: Adjuvant BT after excision of oral cavity SCC provides satisfactory oncological outcomes along with good tolerance. In our study, PDR-BT showed similar oncological and functional results to LDR-BT in this indication.

Oral cavity squamous cell carcinomas in patients with no identified risk factors: Feeling like an outsider.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCCs) mainly affect smokers and drinkers. However, oral cavity squamous cell cancers (OCSCCs) are increasingly affecting patients with no identified risk factors (NIRFs). This study aimed at characterising their experience of the disease. METHODS: Qualitative study based on semi-structured interviews of 20 survivors of OCSCC with NIRF. Methods used in grounded theory approach were applied. RESULTS: Patients with NIRF had a similar experience to that of patients with risk factors regarding treatments. The absence of identified causes led to stigma and led the patients to distance themselves, both from the stereotypic HNSCC cancer patient and the identity as a cancer patient. Furthermore, having no identified risk factors seemed to reinforce the fear of recurrence. CONCLUSION: This study is the first to address key gaps in knowledge regarding patients with NIRF having survived OCSCC. Their experience is similar to that of patients with orphan diseases. Owing to confrontation with other patients and the repeated questions of caregivers about tobacco/alcohol consumption, these patients felt stigmatised during their treatment. OCSCC patients with NIRF may benefit from guidance and support on how to engage in prevention.

Functional and oncological outcomes of salvage transoral robotic surgery: a comparative study.

PURPOSE: Transoral robotic surgery (TORS) as a first-line therapy has been well-documented but evidence is missing regarding salvage therapy. The aim of this study is to compare the oncological and functional outcomes of TORS as a primary and salvage therapy. METHODS: This retrospective monocentric study included 74 patients operated by a single surgeon and sorted out into two groups: primary treatment (PT) or Salvage treatment (ST) in case of previous history of radiation therapy. Patients were further stratified by tumour location: larynx and pharynx (lST vs lPT and pST vs pPT). RESULTS: Forty-eight patients were included in PT group (64.9%) and 26 in ST group (35.1%). ST patients had more frequent cTis/T1 tumours (57.7% vs 29.2%, p = 0.0164) and no clinical lymph disease (3.8% vs 37.5%, p = 0.0016). Tracheostomy was more often performed in the ST group (57.7% vs 16.7%, p = 0.0003) and the lST subgroup (88.9% vs 9.1%, p < 0.0001). Gastric feeding tube placement was more frequent in the ST group (76.9% vs 33.3%, p = 0.0003), the pST subgroup (64.7% vs 15.4%, p = 0.0009) and the lST subgroup (100% vs 54.5%, p = 0.0297). We observed a trend for more postoperative complications in the ST group (69.2% vs 47.9%, p = 0.0783). The overall survival was lower in the ST group (p = 0.0004), and in the pST subgroup (p < 0.0001). The disease-free survival rate was lower in the ST group (p = 0.0001), the pST subgroup (p = 0.0002) and the lST subgroup (p = 0.0328). CONCLUSION: This study confirms that survival and functional outcomes after salvage TORS are worse than in first line surgery.

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.

Toward a doxorubicin-loaded bioinspired bone cement for the localized treatment of osteosarcoma.

Aims: Osteosarcoma represents the second most common cause of death in children and young adults. No biomaterial allowing local drug delivery has been specifically developed. However, a biocompatible bioactive implantable material could prevent some amputations, and the local release of an antitumor agent could limit risks of relapse and metastasis. Methods: We propose a proof of concept of a self-setting paste combining amorphous calcium phosphate and doxorubicin-loaded particles of bone-like carbonated nanocrystalline apatite, as a means of local release. Results: The cement formulation and doping, first with folic acid and then with doxorubicin, was successful. Its physicochemistry was scrutinized. Preliminary in vivo data on an invasive osteosarcoma rat model suggest a limiting effect on metastatic events in the lungs without signs of toxicity.

Contribution of narrow band imaging in delineation of laryngopharyngeal superficial cancer spread: a prospective study.

PURPOSE: The aim of this study was to assess the performance of Narrow Band Imaging (NBI) added to White Light (WL) in the delineation of laryngopharyngeal superficial cancer spread during office-based transnasal flexible endoscopy. METHODS: This bi-centric prospective study was conducted between October 2014 and December 2017. We included consecutive patients with laryngopharyngeal malignant tumors. Transnasal flexible endoscopy was performed by two endoscopists who were blinded to each other's assessments and who examined each patient independently. The first endoscopist only performed a WL examination, while the second endoscopist carried out both WL and NBI. The extent of tumor involvement was reported based on predefined anatomical sub-units. Biopsies in NBI + /WL- sub-units were subsequently performed during panendoscopy. RESULTS: Eighty-four patients were included in the study. A total of 72 NBI + /WL- sub-units were sampled in 38 patients, and 37 of the biopsies were positive (51.4%): 16 for invasive carcinoma, 17 for high-grade dysplasia/carcinoma in situ and 4 for low-grade dysplasia. Ultimately, 26.2% of patients had at least one positive biopsy in an NBI + /WL- sub-unit and, therefore, a better tumor delineation. The clinical T stage was upgraded in 4.8% of cases examined. CONCLUSION: Adding NBI to WL imaging during transnasal flexible endoscopy in patients presenting with laryngopharyngeal pre-malignant or malignant lesions improves the delineation of superficial cancer spread, thereby leading to better adapted treatments. Clinicaltrials.gov registration number: NCT02035735.

Multicentre evaluation of the interest in planned surgery for mandibular reconstruction with fibula free flap: a retrospective cohort study.

PURPOSE: The aim of this study was to determine the impact and cost-effectiveness of virtual surgical planning during fibula free flap mandibular reconstruction on peri- and postoperative data. METHODS: We conducted a retrospective cohort study from January 2012 to December 2016 in four French university centres. RESULTS: Three hundred fibula free flaps for mandibular reconstruction were performed in 294 patients. Surgeries were planned in 29.7% of cases (n = 89). There was no significant difference in the rate of negative-margins excision, median length of hospital stay, operative time, and early complications between planned and non-planned surgeries. Morphological analysis revealed a higher rate of centred occlusion in planned patients (satisfactory alignment of interincisal points: Planned 65.5% vs Non-Planned 33.3%, p = 0.006). CONCLUSION: In mandibular reconstruction by fibula free flap, the additional cost generated by virtual surgical planning does not seem to be balanced by savings resulting from a shorter operative course, a reduced hospital stay, or a reduction in postoperative complications. However, virtual surgical planning may provide a higher rate of centred occlusion. Long-term benefits should be assessed by further studies.

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.

The super thin external pudendal artery (STEPA) free flap for oropharyngeal reconstruction - A case report.

The radial forearm flap is one of the most used micro-anastomotic flaps in cervicofacial reconstruction in a carcinological context. This flap is an ideal in terms of reliability and fineness; it has, however, some disadvantages in terms of the functional and aesthetic complications of its donor site. In alternative to a radial forearm free flap, we report the use of the free super thin external pudendal artery flap (STEPA flap) for an oropharyngeal reconstruction. The aim was to decrease the donor site morbidity. A 71-years-old man with a T2N0M0 oropharyngeal squamous cell carcinoma has undergone surgical treatment. A left STEPA free flap was performed to reconstruct a defect about 8 × 6 cm2 . This flap was designed as a half-scrotal free flap sized 9 × 7 cm2 and was inset after tunneling of the pedicle at the floor of the mouth. A surgical revision was needed on the 15th day postoperative for disunion. There was no skin flap failure. After 12 month of follow-up, no complication was observed at the donor site and no erectile dysfunction was recorded. Its characteristics in terms of fineness, flexibility, ease of conformation, and pedicle length are similar to those of the radial forearm flap with less aesthetic and functional sequelae of the donor site. The STEPA flap may be a promising free flap in oropharyngeal or oral cavity reconstruction.

Interaction of Folic Acid with Nanocrystalline Apatites and Extension to Methotrexate (Antifolate) in View of Anticancer Applications.

Nanocrystalline apatites mimicking bone mineral represent a versatile platform for biomedical applications thanks to their similarity to bone apatite and the possibility to (multi)functionalize them so as to provide "à la carte" properties. One relevant domain is in particular oncology, where drug-loaded biomaterials and engineered nanosystems may be used for diagnosis, therapy, or both. In a previous contribution, we investigated the adsorption of doxorubicin onto two nanocrystalline apatite substrates, denoted HA and FeHA (superparamagnetic apatite doped with iron ions), and explored these drug-loaded systems against tumor cells. To widen their applicability in the oncology field, here we examine the interaction between the same two substrates and two other molecules: folic acid (FA), often used as cell targeting agent, and the anticancer drug methotrexate (MTX), an antifolate analogue. In a first stage, we investigated the adsorptive behavior of FA (or MTX) on both substrates, evidencing their specificities. At low concentration, typically under 100 mmol/L, adsorption onto HA was best described using the Sips isotherm model, while the formation of a calcium folate secondary salt was evidenced at high concentration by Raman spectroscopy. Adsorption onto FeHA was instead fitted to the Langmuir model. A larger adsorptive affinity was found for the FeHA substrate compared to HA; accordingly, a faster release was noticed from HA. In vitro tests carried out on human osteosarcoma cell line (SAOS-2) allowed us to evaluate the potential of these compounds in oncology. Finally, in vivo (subcutaneous) implantations in the mouse were run to ascertain the biocompatibility of the two substrates. These results should allow a better understanding of the interactions between FA/MTX and bioinspired nanocrystalline apatites in view of applications in the field of cancer.

Cetuximab-Carboplatin-5-Fluorouracil Regimen in Elderly Patients with Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A French Retrospective Survey.

BACKGROUND: The cetuximab plus platinum-based chemotherapy regimen is a standard of care in the treatment of recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The feasibility in the elderly population is currently unknown. METHODS: We performed a retrospective study in order to assess the efficacy and safety of the cetuximab plus platinum-based chemotherapy regimen in patients >65 years with recurrent or metastatic HNSCC. We performed a retrospective review of all medical records from recurrent or metastatic HNSCC patients >65 years treated with the cetuximab plus platinum-based chemotherapy regimen between September 2008 and December 2013 in our institution (Centre Paul Strauss, Strasbourg, France). RESULTS: A total of 59 patients were identified. Carboplatin in combination with 5-fluorouracil (FU) was the only cetuximab-associated chemotherapy regimen used for treating elderly patients. The median progression-free survival was 4 months (95% confidence interval [CI]: 2.9-4.7), and the median overall survival was 9.1 months (95% CI: 6.5-13.1). Grade 3 or 4 toxicity adverse events occurred in 52% (n = 31) of the patients (mostly hematologic toxicities and infections). CONCLUSIONS: This retrospective study suggests that the cetuximab plus carboplatin-5FU chemotherapy is an effective treatment option for elderly patients with recurrent or metastatic HNSCC.

The transverse musculo-cutaneous gracilis flap for breast reconstruction: How to avoid complications.

BACKGROUND: The transverse musculocutaneous gracilis (TMG) flap has become a common solution for breast reconstruction. However, the safe skin paddle limits are not yet understood. In this study, we attempted to address this issue based on our experiences with inferior and posterior skin paddle extension. METHODS: Forty-four breast reconstructions with TMG flaps performed between November 2010 and January 2014 were analyzed retrospectively. For the first 20 cases, the flap skin paddle was extended 3 cm posteriorly to the middle thigh (group 1). For the next 20 flaps (group 2), the posterior tip was limited to this line, whereas more fat was recruited inferiorly. In the four cases of group 3, the skin flap was extended posteriorly with a second vascular pedicle from the profunda artery perforator (PAP) flap. The weights and the dimensions of the flaps, operating durations, and postoperative complications of the entire series were analyzed. Groups 1 and 2 were statistically compared. RESULTS: Flap complications were statistically more frequent in group 1 compared with group 2 (45 vs. 0%, P = 0.0012); 40% posterior flap tip necrosis was observed in group 1. Conversely, donor site complications were statistically more frequent in group 2 than in group 1 (40 vs. 5%, P = 0.019) with 35% inner thigh dehiscence. In the TMG with extended PAP flap group, the operating duration was 77 min longer compared with the rest of the series with no donor site complications. In one case, limited necrosis occurred at the anterior skin tip. CONCLUSIONS: Harvesting the posterior portion of the TMG up to the middle of the posterior thigh may lead to partial flap necrosis. Extending subcutaneous fat removal under the inferior skin incision may increase the risk of donor site complications. Adding a second vascular pedicle from the PAP flap may improve posterior TMG tip perfusion at the expense of a longer operation.

Videofluoroscopic swallowing study to detect pharyngeal leak after total (pharyngo-) laryngectomy: Retrospective assessment of a single-institution protocol.

BACKGROUND: We aimed to assess the effectiveness of a single-institution protocol of videofluoroscopic swallowing study (VFSS) for the detection of pharyngeal leak (PL) and its usefulness to mitigate evolution into subsequent pharyngocutaneous fistula (PCF) after total (pharyngo-) laryngectomy (TL). METHODS: This retrospective single-center study was conducted between February 2014 and December 2022. We included all patients who underwent TL and performed a VFSS between Day 7 and Day 14 postoperatively to detect a subclinical PL. RESULTS: Two-hundred and forty-eight patients met the inclusion criteria. Among the 186 patients (75%) with a negative VFSS, 11 patients (5.9%) developed a secondary PCF after oral intake resumption (false negative of VFSS). Among the 62 patients (25%) with a positive VFSS, the occurrence of a PCF was avoided in 59.7% of cases. CONCLUSION: This study showed a good effectiveness of VFSS in the detection of PL after TL, alongside a usefulness to mitigate evolution into subsequent PCF.

Prognostic implications of mucosal and deep margin distances according to T-status in oral tongue squamous cell carcinoma: A single-center retrospective study.

OBJECTIVE: To elucidate the prognostic implications of mucosal and deep margin distances in oral tongue squamous cell carcinoma (OTSCC), and to assess a different margin cut-off value in T1-T2 versus T3-T4 tumors. METHODS: This single-center retrospective study included 223 patients who received surgery for a primary OTSCC between January 2017 and December 2021. RESULTS: Multivariable analysis showed that deep margin distance ≥3 mm in T1-T2 tumors and ≥5 mm in T3-T4 tumors was significantly associated with better RFS and OS. Mucosal and deep margin distances were globally clinically useful for 2-year RFS prediction of T1-T2 tumors, for which deep margins seemed to have more clinical utility than mucosal margins. The influence of margin distances on 2-year RFS seemed greater for T1-T2 tumors than T3-T4 tumors. CONCLUSION: Mucosal and deep margin distances were associated with OS and RFS in OTSCC. Shorter deep margin distances may be aimed for in T1-T2 versus T3-T4 tumors.

Advanced Platelet Lysate Aerogels: Biomaterials for Regenerative Applications.

Human platelet lysate (HPL), rich in growth factors, is increasingly recognized for its potential in tissue engineering and regenerative medicine. However, its use in liquid or gel form is constrained by limited stability and handling difficulties. This study aimed to develop dry and porous aerogels from HPL hydrogel using an environmentally friendly supercritical CO2-based shaping process, specifically tailored for tissue engineering applications. The aerogels produced retained their three-dimensional structure and demonstrated significant mechanical robustness and enhanced manageability. Impressively, they exhibited high water absorption capacity, absorbing 87% of their weight in water within 120 min. Furthermore, the growth factors released by these aerogels showed a sustained and favourable biological response in vitro. They maintained the cellular metabolic activity of fibroblasts (BALB-3T3) at levels akin to conventional culture conditions, even after prolonged storage, and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Additionally, the aerogels themselves supported the adhesion and proliferation of murine fibroblasts (BALB-3T3). Beyond serving as excellent matrices for cell culture, these aerogels function as efficient systems for the delivery of growth factors. Their multifunctional capabilities position them as promising candidates for various tissue regeneration strategies. Importantly, the developed aerogels can be stored conveniently and are considered ready to use, enhancing their practicality and applicability in regenerative medicine.

[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.