Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We ...aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.
A 46-year-old female presented with a 4-month history of 5–30 mm subcutaneous nodules in the right supraclavicular, axillary, and pectoral areas (Fig. 1). She had undergone a lobo-isthmectomy for a ...20 mm right follicular adenoma performed 8 years earlier by robot-assisted transaxillary surgery (RATS). Benign colloid and thyroid cells were found in two successive fine needle aspirations. The CT scan revealed an ill-defined infiltrative lesion in the right central compartment with muscle and internal jugular vein invasion demonstrating a locally aggressive behavior. We suspected that malignant thyroid cells were seeding the tract of the transaxillary approach.
In patients with head and neck squamous cell carcinoma (HNSCC), cetuximab a monoclonal antibody targeting epidermal growth factor receptor (EGFR) has been shown to improve overall survival when ...combined with radiotherapy in the locally advanced setting or with chemotherapy in first-line recurrent and/or metastatic (R/M) setting, respectively. While biomarkers of resistance to cetuximab have been identified in metastatic colorectal cancer, no biomarkers of efficacy have been identified in HNSCC. Here, we aimed to identify biomarkers of cetuximab sensitivity/resistance in HNSCC.
HNSCC patients treated with cetuximab at the Curie Institute, for whom complete clinicopathological data and formalin-fixed paraffin-embedded (FFPE) tumor tissue collected before cetuximab treatment were available, were included. Immunohistochemistry analyses of PTEN and EGFR were performed to assess protein expression levels.
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mutations were analyzed using high-resolution melting (HRM) and Sanger sequencing. We evaluated the predictive value of these alterations in terms of progression-free survival (PFS).
Hot spot activating
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mutations were associated with poor PFS among HNSCC patients treated with cetuximab in the first-line R/M setting, but not among HNSCC patients treated with cetuximab in combination with radiotherapy. Loss of PTEN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and radiotherapy. High EGFR expression did not predict cetuximab sensitivity in our patient population.
Hot spot activating
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mutations predicted cetuximab resistance among HNSCC patients in the first-line R/M setting, whereas loss of PTEN protein expression predicted resistance to cetuximab when combined to radiotherapy.
Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to ...determine a robust biomarker for severe OCSCC, using a biology-driven strategy.
Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort.
Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1.
High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens.
This study aimed to assess the efficacy of utilizing the internal jugular vein (IJV) as the primary recipient site for venous anastomoses in head and neck oncological reconstruction. Patients who ...underwent a free flap reconstruction of the head and neck were retrospectively included. Venous anastomoses were preferentially performed less than 1 cm from the IJV, either end-to-side (EtS) on the IJV, or end-to-end (EtE) on the origin of the thyrolingofacial venous (TLF) trunk. When the pedicle length was insufficient to reach the IJV, anastomoses were performed EtE to a size-matched cervical vein.
Of the 246 venous anastomoses, 216 (87.8%) were performed less than 1 cm from the IJV, including 150 EtS on the IJV (61.0%), and 66 EtE on the TLF trunk (26.8%). Thirty veins (12.1%) were anastomosed EtE on other cervical veins more than 1 cm from the IJV. Two venous thromboses occurred (0.9%) and were successfully managed after revision surgery. There was no evidence of an increased thrombosis rate in high-risk or pre-irradiated patients. These findings suggest that the internal jugular vein is safe and reliable as a first-choice recipient vessel for free flap transfers in head and neck oncological reconstruction.
Nivolumab and pembrolizumab targeting programmed cell death protein 1 (PD-1) have recently been approved among patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) ...who failed platinum therapy. We aimed to evaluate the prognostic value of selected immune gene expression in HNSCC.
We retrospectively assessed the expression of 46 immune-related genes and immune-cell subpopulation genes including immune checkpoints by real-time polymerase chain reaction among 96 patients with HNSCC who underwent primary surgery at Institut Curie between 1990 and 2006. Univariate and multivariate analyses were performed to assess the prognostic value of dysregulated genes.
The Median age of the population was 56 years range: 35–78. Primary tumour location was oral cavity (45%), oropharynx (21%), larynx (18%) and hypopharynx (17%). Twelve patients (13%) had an oropharyngeal human papillomavirus–positive tumour. Most significantly overexpressed immune-related genes were TNFRSF9/4-1BB (77%), IDO1 (75%), TNFSF4/OX40L (74%) and TNFRSF18/GITR (74%), and immune-cell subpopulation gene was FOXP3 (62%). Eighty-five percent of tumours analysed overexpressed actionable immunity genes, including PD-1/PD-L1, TIGIT, OX40/OX40L and/or CTLA4. Among the immune-related genes, high OX40L mRNA level (p = 0.0009) and low PD-1 mRNA level (p = 0.004) were associated with the highest risk of recurrence. Among the immune-cell subpopulation genes, patients with high PDGFRB mRNA level (p < 0.0001) and low CD3E (p = 0.0009) or CD8A mRNA levels (p = 0.004) were also at the highest risk of recurrence.
OX40L and PDGFRB overexpression was associated with poor outcomes, whereas PD-1 overexpression was associated with good prognosis in patients with HNSCC treated with primary surgery, suggesting their relevance as potential prognostic biomarkers and major therapeutic targets.
•Most significantly overexpressed genes were 4-1BB, IDO1, OX40L, GITR and FOXP3.•Eighty-five percent of tumours overexpressed actionable genes such as PD-1/PDL-1, TIGIT, OX40/OX40L and/or CTLA4.•High OX40L or PDGFRB mRNA level was associated with the highest risk of recurrence.•Low PD-1 or CD3E or CD8A mRNA levels were associated with the highest risk of recurrence.
Objectives To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node ...involvement among tumor characteristics. Methods All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses. Results Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution. Conclusion Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement. Level of Evidence IV Laryngoscope , 2024
Reconstruction post-orbital exenteration serves the dual purpose of expediting healing, laying the groundwork for cosmetic restoration, and minimising complications such as orbitosinusal fistulae. ...The aim of this study was to introduce a modified "Ice cream cone" (ICC) design of the Radial Forearm Free Flap (RFFF) technique used for reconstruction of orbital exenteration cavity, along with the oncological, functional, and aesthetic outcomes.
The authors conducted a retrospective study between January 2005 and December 2020. Inclusion criteria encompassed patients treated for orbitosinusal malignancies undergoing exenteration with subsequent ICC design of RFFF reconstruction.
Twenty-two patients underwent exenteration with the ICC design of RFFF. At the follow-up conclusion, 65% of patients regularly used orbital prosthesis. The average waiting time until the prosthesis was 10 months. Quality of life questionnaires yielded average RFFF POSAS scores of 23.5 (SD 13,6), cervical POSAS scores of 8 (SD 13,2), and orbital cavity rehabilitation scores of 5.9 (SD: 3,32).
ICC design of RFFF is a reliable technique. It can be proposed in cases of extended exenteration with a high risk of cerebrospinal fluid (CSF) but more generally in cases of total exenteration. This technique facilitates optimal postoperative wound healing and accommodates early radiotherapy. Importantly, the bowl-shaped aspect of the orbital socket supports effective prosthetic rehabilitation for patients opting for orbital prosthesis post-surgery.
Limited evidence exists regarding the 2‐deoxy‐2‐fluorine‐18‐fluoro‐D‐glucose (FDG) avidity of Warthin tumors, the second most common benign parotid gland tumor. This study aims to clarify this aspect ...by analyzing patients who underwent FDG positron emission tomography/computed tomography (PET/CT) and quantifying tumor standardized uptake values (SUV). Medical records of 29 patients with fine needle aspiration (FNA)‐confirmed Warthin tumors who underwent FDG‐PET/CT near the diagnosis of Warthin tumor were reviewed. Key parameters included cancer history, cytologic diagnosis of Warthin tumor, maximum SUV on FDG PET/CT, and tumor localization. Among the cohort, 18 males and 11 females (average age: 67.9 years) were included. Most patients had malignant neoplasms (lung, head and neck, breast, others). One patient had synchronous liver cancer. Three individuals had bilateral Warthin tumors, and three had bifocal tumors, resulting in 35 tumors for analysis. Tumors were located in the parotid gland (28) and vicinity (7). SUVmax for the Warthin tumors ranged from 3.6 to 26.8, with an average SUVmax of 10.1. Warthin tumors exhibit significant and variable FDG accumulation, exceeding expectations and mimicking high‐grade malignancies. Awareness of this phenomenon is crucial for accurate staging and timely management. In cases of positive FDG PET/CT uptake in periparotid, perimandibular, and upper jugular areas, FNA is recommended to avoid misinterpretation or delays in management.
Surgery for head and neck cancer often requires free flap reconstructions, whose harvesting site often requires a thin-skin graft. Wounds from the thin-skin donor site are comparable to an ...intermediate or deep second-degree burn. This is uncomfortable and can lead to complications such as a long healing time, local infections and pain. Since they are reproducible, these wounds may serve as a model for an objective assessment of new healing medical devices. The acellular fish skin matrix is a new medical device designed to improve healing quality and time.
We compared the outcomes between standard procedure and the use of this matrix placed on the split-thickness skin graft (STSG) donor site, in patients operated on in our centre for radial forearm free flap reconstruction for head and neck wounds.
There were 21 patients included. The healing time was halved when using the acellular fish skin matrix, from 68 to 32 days on average. Acellular fish skin matrix reduced pain levels and local infection. The visual analogue pain scale (VAS) was ≥3 at five days (p=0.0034) and infection rate reduced from 60% to 0% (p=0.0039).
These results are extremely encouraging. However, it is important to take into account the relatively high cost of this matrix for its future indications. A larger study including an overall cost estimation and an assessment on different wound types would be interesting, to better target the indications of the acellular fish skin matrix.
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