Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and ...cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in
(encoding pP53 protein),
(encoding cyclin dependent kinase inhibitor 2A),
(encoding FAT atypical cadherin 1), and
(encoding lysine methyltransferase 2D), with the exception of
(encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.
The aim of this study was to evaluate the reliability of magnetic resonance imaging (MRI) in detecting disc perforations in the temporomandibular joint (TMJ), and to establish diagnostic criteria for ...this purpose. The retrospective analysis included patients who had undergone preoperative MRI and TMJ arthroscopy at the same hospital. Direct and indirect signs of disc abnormalities on MRI were compared with arthroscopic findings of disc perforation. Out of 355 joints evaluated in 185 patients, arthroscopy confirmed disc perforations in 14.7% of cases. Several MRI findings were significantly associated with disc perforation, including anterior disc displacement without reduction (ADDwoR), signal alterations in the mid-disc area, disc deformity (SAMD), retrocondylar disc fragments, osteophytes, condylar bone marrow degeneration (CBMD), and joint effusion in both joint spaces (ESJS-EIJS). Regression analysis revealed that SAMD, osteophytes, and CBDM were strongly associated with disc perforation. The ROC curve showed that MRI had an AUC = 0.791, with a sensitivity of 88.5% and a specificity of 61.5%. Two diagnostic methods, one based on three findings (osteophytes, ADDwoR, and SAMD) and one based on two direct signs (ADDwoR and SAMD), yielded high sensitivity and specificity values of 80.4% and 69.8%, and 84.3% and 62.5%, respectively. In conclusion, MRI demonstrated acceptable accuracy in the detection of TMJ disc perforations, with specific diagnostic criteria offering high sensitivity and specificity. Significant MRI indicators of disc perforation included SAMD, osteophytes, and CBDM. This study provides valuable information on the use of MRI as a diagnostic tool for TMJ disc perforations.
Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our ...institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among
= 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among
= 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (
= 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (
= 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.
Background: Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is ...crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These issues can lead to functional impairments, including difficulties in chewing, swallowing, and speech. The fibula flap is widely used for mandibular reconstruction due to its long bone segment and robust vascular supply, though it may not always provide adequate bone height for optimal dental rehabilitation. This systematic review aims to determine if the double-barreled fibula flap (DBFF) configuration is a viable alternative for mandibular reconstruction and to evaluate the outcomes of dental implants placed in this type of flap. Materials and Methods: This study adhered to the Cochrane Collaboration criteria and PRISMA guidelines and was registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols Database (INPLASY2023120026). We included clinical studies published in English, Spanish, or French that focused on adult patients undergoing segmental mandibulectomy followed by DBFF reconstruction and dental rehabilitation. Data sources included Medline/PubMed, the Cochrane Library, EMBASE, Scopus, and manual searches. Two reviewers independently screened and selected studies, with discrepancies resolved by a third reviewer. Data extraction captured variables such as publication year, patient demographics, number of implants, follow-up duration, flap survival, implant failure, and aesthetic outcomes. The risk of bias was assessed using the JBI appraisal tool, and the certainty of evidence was evaluated using the GRADE approach. Results: A total of 17 clinical studies were included, evaluating 245 patients and 402 dental implants. The average patient age was 43.7 years, with a mean follow-up period of 34.3 months. Flap survival was high, with a 98.3% success rate and only four flap losses. The implant failure rate was low at 1.74%. Esthetic outcomes were varied, with only three studies using standardized protocols for evaluation. The overall certainty of evidence for flap survival was moderate, low for implant failure, and very low for aesthetics due to the subjective nature of assessments and variability in reporting. Conclusions: The primary limitations of the evidence included in this review are the observational design of the studies, leading to an inherent risk of bias, inconsistency in reporting methods, and imprecision in outcome measures. Additionally, the subjective nature of aesthetic evaluations and the variability in assessment tools further limit the reliability of the findings. The DBFF technique demonstrates excellent outcomes for mandibular reconstruction, with high flap survival and low implant failure rates, making it a viable option for dental rehabilitation. However, the evidence for aesthetic outcomes is less certain, highlighting the need for more rigorous and standardized research. This review supports the DBFF as a good alternative for mandibular reconstruction with successful dental implant integration, although further studies are needed to enhance the reliability of aesthetic evaluations.
Pembrolizumab (P) is approved in the first-line (1L) setting in patients with squamous cell carcinoma of the head and neck (SCCHN) with a CPS ≥ 1 and has shown promising activity in the ...locally-advanced (LA) setting. However, there are no alternatives for patients who are platinum-5FU (PF)-unfit and in need of a rapid tumor response. Taxanes are active agents in SCCHN that could effectively substitute 5FU as shown in Keynote-B10, Frail-Immune and DEPEND trials 1-3. We evaluated the combination of pembrolizumab plus platinum and taxanes (PCT) +/- prophylactic (p) G-CSF in PF-unfit patients at our institution.
Retrospective study of patients diagnosed with SCCHN and treated with PCT at Hospital Clínico Universitario San Carlos, Madrid (Spain). A descriptive study, as well as objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety in the 1L and in the LA setting, were analyzed.
Within the period August 2019 - October 2023, 18 patients (1L: n=6; LA: n=12) were identified. Among 1L: Male/Female: 2/4; age: 65y (56-86). Subsite: oral cavity (OC): n=5, larynx (n=1). Median CPS: 40 (5-80). No. combo PCT cycles: 6 (2-9). No. maintenance P cycles: 4 (1-8). ORR: 67% (2 CR, 2 PR, 2 SD). After a median follow-up (F-U) of 9 months (m) (1 -25), median PFS and OS were 8 m (4.7 - 11.3) and NR (NR-NR), respectively. pG-CSF in 4/6 pts. G3/4 toxicity: G3 neutropenia: 4/6, G3 thrombopenia: 1/6. There were no toxic deaths. Among LA: Male/Female: 8/4; age: 72y (47-96). P + wkCBDCA-paclitaxel: n=10/12; P + 3wkCBDCA-paclitaxel: n=1/12, P + 3wkCDDP-docetaxel: n=1/12. Subsite: oropharynx: n=3, OC: n=5, CUP: n=1, Sinonasal: n=3. Median CPS: 30 (3-100). No. combo PCT cycles: 3 (2-4). No. maintenance P cycles: 0 (0-4). ORR after PCT (n=10): 90% (4 CR, 5 PR, 1 PD). Post-PCT Tx: Surgery: n=3; CRTx: n=5; Maint P: n=6. After a median follow-up (F-U) of 4 m (0-34), median PFS and OS were 6 m (NR - NR) and NR (NR-NR), respectively. pG-CSF in 6/12 pts. G3/4 toxicity: G3 neutropenia: 6/12, G3 thrombopenia: 4/12, G3 pneumonia: 1/12, G3 IR-colitis: 1/12, G4 IR-transaminitis: 1/12. There were no toxic deaths.
Updated results for the LA population (as of March 2024) will be presented at the meeting.
PCT and particularly weekly PCT +/- pG-CSF is a highly effective and safe chemoimmunotherapy option for PF-unfit patients in need of a rapid response and a positive CPS, both in the 1L and LA settings. Trials with weekly PCT should be conducted in comorbid and/or elderly patients with LA and R/M SCCHN not candidates for high-dose CT and in need of rapid response.
Purpose To assess the efficacy of neuro-reflexotherapy intervention (NRT) for treating temporomandibular joint dysfunction attributed to myofascial pain. Neuro-reflexotherapy intervention consists of ...the temporary implantation of epidermal devices in trigger points in the back and ear. It has shown efficacy, effectiveness, and cost-effectiveness in treating subacute and chronic common back pain. No study, however, has explored its efficacy in treating myofascial temporomandibular joint pain (MF/TMJP). Patients and Methods This was a randomized, double-blind, placebo-controlled trial. Patients with MF/TMJP for more than 3 months in spite of conservative treatment, and with no evidence of major structural damage in the joint, were recruited at the Maxillofacial Department of the Hospital Clínico Universitario, a teaching hospital in Madrid, Spain. Patients were randomly assigned to an intervention group and to a control group. Patients in the treated group underwent 2 NRTs, immediately after baseline assessment and 45 days later. Sham interventions in the control group consisted of placement of the same number of epidermal devices within a 5-cm radius of the target zones. In both groups, conservative treatment during follow-up was allowed and recorded. Patients underwent clinical evaluations on 4 occasions: 5 minutes before intervention, 5 minutes after intervention, and 45 and 90 days later. The preintervention assessment was performed by the physician at the hospital service who included the patient in the study. The 3 follow-up assessments were performed independently by 1 of 2 physicians who had no connection with the research team, and who were blinded to patients' assignments. The primary outcome variable was level of pain severity during jaw movements at the last assessment (90 days), and the key comparison of interest was change in pain over time (pain levels at baseline and at 90 days). Level of pain was measured using a visual analog scale (VAS). Results Fifty-one patients with MF/TMJP were recruited into the study. Random assignment allocated 27 patients to the intervention group, and 24 to the control group. Differences in pain severity in favor of the intervention group appeared immediately after the intervention, persisted for 45 days, and increased after the second intervention. Differences at last follow-up were highly clinically and statistically significant (4 to 5 points on the VAS, P = .000), allowing for patients in the intervention group to cease drug treatment ( P = .005). There were no differences in the evolution of crepitus or clicking in the joint. There were no clinically relevant side effects associated with the intervention. Conclusions For patients in whom conservative treatment has failed, NRT improves the chronic pain associated with MF/TMJP syndrome.
Mandibular third molar (MTM) extraction is one of the most frequently performed surgeries in the oral cavity. Establishing the level of surgical difficulty pre-operatively is an essential step to ...ensure correct treatment planning. In Spain, MTM extraction - especially in cases presenting greater difficulty - is normally performed by doctors specializing in oral and maxillofacial surgery, or by dentists with postgraduate qualifications in oral surgery. The present work set out to analyze the extent to which perceptions of surgical difficulty of the said intervention vary in relation to professional training.
This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal-Wallis test) were applied.
A total of 213 surveys were available for analysis. Both groups awarded the greatest importance to clinical experience, followed by anatomical and radiographic factors, root morphology obtaining the highest score among anatomical factors (9.01±1.42), while proximity of the MTM to the inferior alveolar nerve was regarded as the least important anatomical factor (8.11±2.54). Significant differences were only found for patient age, whereby maxillofacial surgeons awarded this factor more importance than dentists.
The different training received by dentists specialized in oral surgery and maxillofacial surgeons did not influence either perceptions of surgical difficulty of MTM extraction, or opinions as to the factors influencing surgical difficulty.
Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fiuoropyrimide-ineligible patients with recurrent or metastatic squamous cell ...carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2,80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients all grade 3 (anemia, neutropenia, thrombopenia, hypertension). The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN. Key words: chemoimmunotherapy, pembrolizumab, anti-programmed cell death protein 1, carboplatin, paclitaxel, head and neck cancer
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