Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2.

AIMS: Salivary gland neoplasms (SGN) exhibiting the HMGA2::WIF1 fusion are recognized by their resemblance to histology found in canalicular adenoma. Recently, ~20% of cases among 28 HMGA2::WIF1-rearranged-SGN showed malignancy and adverse outcomes (recurrence, distant metastasis, and disease-specific mortality). Among them, MDM2/CDK4 amplifications were identified in one case. This outcome suggests that the MDM2/CDK4 amplifications could be useful to predict an aggressive course of carcinoma ex-pleomorphic adenoma (CEPA). METHODS AND RESULTS: We investigated the correlation between HMGA2 fusion and MDM2 amplification in four salivary gland neoplasms, providing detailed clinicopathological features and outcomes. Cases were selected from different institutions. Histological examination, immunohistochemistry, fluorescence in situ hybridization (FISH), RNA sequencing, and whole-exome capture were performed. The cohort included four CEPA cases, all female, aged between 32 and 89 years. Tumours arose from the parotid gland with an average size of 24.5 mm. None exhibited recurrence or distant metastases during the 4-5 months of follow-up. Pathologically, all cases displayed a peculiar atypical nuclei with 'gear-like appearance'. Immunohistochemically, tumours exhibited a biphasic pattern with myoepithelial and ductal differentiation markers. All cases showed HMGA2 overexpression and MDM2 amplification by FISH and RNA sequencing. In a control cohort of MDM2 nonamplified CEPA cases, not exhibiting the peculiar nuclear atypia. CONCLUSIONS: Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Transoral Laser Microsurgery versus Robot-Assisted Surgery for Squamous Cell Carcinoma of the Tongue Base (Oncological and Functional Results)-A Retrospective GETTEC Multicenter Study.

The base of the tongue (BOT) is the second most common site for squamous cell carcinoma (SCC) in the oropharynx. There are currently no clear guidelines for the management of BOT SCC. Our main objective was to compare the oncological outcomes of two minimally invasive approaches, transoral laser microsurgery (TLM) and transoral robot-assisted surgery (TORS). This was a retrospective French GETTEC (Groupe d'Études des Tumeurs de la Tête et du Cou) multicenter study of patients with BOT SCC removed surgically either by TLM or TORS between 2005 and 2021. The study group included 16 patients treated by TLM and 38 by TORS, with median follow-up times of 14.4 and 37.2 months, respectively. The overall survival (OS) rates at 2 and 3 years were 67% in the TLM group and 90% at 2 years and 86% at 3 years in the TORS group (p = 0.42, p = 0.20). There was no significant difference in recurrence-free survival (RFS) between the two techniques after 2 and 3 years. The tumors removed by TORS were significantly larger. Operative times were significantly shorter in the TLM group. There were no differences in feeding resumption; none of the patients in the TLM group required a tracheotomy. Postoperative hemorrhagic complication rates were similar in the two groups (12% for TLM and 13% for TORS). Both TORS and TLM showed encouraging oncological, functional, and safety results in BOT SCC even in recurrence or second primary cancer patients, without a technique being found superior in terms of OS or RFS. Tumors removed by TORS were larger without an increase in postoperative bleeding, extending the possibilities of transoral treatment.

A New Animal Model of Laryngeal Transplantation.

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

Osteocutaneous-flap-related osteomyelitis following mandibular reconstruction: a cohort study of an emerging and complex bone infection.

Osteocutaneous flap (OCF) mandible reconstruction is at high risk for surgical site infection. This study aimed to describe diagnosis, management, and outcome of OCF-related osteomyelitis. All patients managed at our institution for an OCF-related osteomyelitis following mandible reconstruction were included in a retrospective cohort study (2012-2019). Microbiology was described according to gold-standard surgical samples, considering all virulent pathogens, and potential contaminants if present on at least two samples. Determinants of treatment failure were assessed by logistic regression and Kaplan-Meier curve analysis. The 48 included patients (median age 60.5 (IQR, 52.4-66.6) years) benefited from OCF mandible reconstruction mostly for carcinoma ( n = 27 / 48 ; 56.3 %) or osteoradionecrosis ( n = 12 / 48 ; 25.0 %). OCF-related osteomyelitis was mostly early ( ≤ 3 months post-surgery; n = 43 / 48 ; 89.6 %), presenting with local inflammation ( n = 28 / 47 ; 59.6 %), nonunion (wound dehiscence) or sinus tract ( n = 28 / 47 ; 59.6 %), and/or bone or device exposure ( n = 21 / 47 ; 44.7 %). Main implicated pathogens were Enterobacteriaceae ( n = 25 / 41 ; 61.0 %), streptococci ( n = 22 / 41 ; 53.7 %), Staphylococcus aureus ( n = 10 / 41 ; 24.4 %), enterococci ( n = 9 / 41 ; 22.0 %), non-fermenting Gram-negative bacilli ( n = 8 / 41 ; 19.5 %), and anaerobes ( n = 8 / 41 ; 19.5 %). Thirty-nine patients (81.3 %) benefited from surgery, consisting of debridement with implant retention (DAIR) in 25 / 39 (64.1 %) cases, associated with 93 (IQR, 64-128) days of antimicrobial therapy. After a follow-up of 18 (IQR, 11-31) months, 24 / 48 (50.0 %) treatment failures were observed. Determinants of treatment outcomes were DAIR (OR, 3.333; 95 % CI, 1.020-10.898) and an early infectious disease specialist referral (OR, 0.236 if ≤ 2  weeks; 95 % CI, 0.062-0.933). OCF-related osteomyelitis following mandibular reconstruction represents difficult-to-treat infections. Our results advocate for a multidisciplinary management, including an early infectious-disease-specialist referral to manage the antimicrobial therapy driven by complex microbiological documentation.

Resection and reconstruction of the carotid artery for head and neck squamous cell carcinoma: a GETTEC study.

OBJECTIVES: Main: To describe 1-year overall survival (OS) after primary or salvage management of head and neck squamous cell carcinoma (HNSCC) invading the common or internal carotid artery (CCA/ICA). Secondary: To assess disease control rate, treatment morbidity, and radio-anatomopathologic correlation. METHODS: Retrospective study of 67 patients, treated between 1999 and 2020 for N3bM0 HNSCC invading the CCA/ICA as identified by CT-scan. Tumors that could not have been resected with a complete en-bloc resection sacrificing and reconstructing the CCA/ICA were excluded. Patients were separated into two groups (primary or salvage treatment) and studied according to the type of treatment they received: radiotherapy/radiochemotherapy (RT/RCT), surgery, or systemic therapy (ST). RESULTS: For newly treated patients, the 1-year OS was significantly better after RT/RCT (73%) than after surgery (40%, p < 0.0001). In the salvage setting, the 1-year OS after surgery (40%) was better than after ST (14%, statistically suggestive difference with p = 0.0241). Surgery improved cervical control, but distant metastases occurred in more than 50% of cases regardless of treatment. No neurological complication occurred after carotid reconstruction. Perioperative mortality was 7% (1/15). The carotid invasion was confirmed by pathological examination in all five patients with an arterial deformation on CT-scan, in seven among eight patients with CCA/ICA encasement greater than 270°, and in four out of seven patients with CCA/ICA encasement between 180° and 270°. CONCLUSION: Neck dissection with carotid resection and reconstruction is technically feasible with acceptable neurovascular morbidity. For newly treated patients, survival is better after RT/RCT. For salvage treatment, surgery could be proposed to selected patients.

Circulating Tumor Cell Detection during Neoadjuvant Chemotherapy to Predict Early Response in Locally Advanced Oropharyngeal Cancers: A Prospective Pilot Study.

Patients with locally advanced oropharyngeal carcinoma treated with neoadjuvant chemotherapy are reassessed both radiologically and clinically to adapt their treatment after the first cycle. However, some responders show early tumor progression after adjuvant radiotherapy. This cohort study evaluated circulating tumor cells (CTCs) from a population of locally advanced oropharyngeal carcinoma patients treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) induction chemotherapy or DCF with a modified dose and fractioned administration. The counts and phenotypes of CTCs were assessed at baseline and at day 21 of treatment, after isolation using the RosetteSepTM technique based on negative enrichment. At baseline, 6 out of 21 patients had CTCs (28.6%). On day 21, 5 out of 11 patients had CTCs (41.6%). There was no significant difference in the overall and progression-free survival between patients with or without CTCs at baseline (p = 0.44 and 0.78) or day 21 (p = 0.88 and 0.5). Out of the 11 patients tested at day 21, 4 had a positive variation of CTCs (33%). Patients with a positive variation of CTCs display a lower overall survival. Our findings suggest that the variation in the number of CTCs would be a better guide to the management of treatment, with possible early changes in treatment strategy.

CD44, γ-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma.

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.

Airway management during transoral robotic surgery for head and neck cancers: a French GETTEC group survey.

PURPOSE: The aim of the survey was to define the indications for preventive tracheostomy in transoral robotic surgery (TORS) for head and neck cancers. METHODS: From October 2019 to January 2020, an online questionnaire was e-mailed to French surgical ENT teams with considerable experience of the TORS procedure (Gettec group). A descriptive analysis of the answers was performed. RESULTS: Eighteen French surgical teams answered the questionnaire. For 77.8% of the surgical teams, a past history of radiotherapy with residual edema was an indication for prophylactic tracheostomy, and for 88.9%, > 75 mg of antiplatelet medication or anticoagulation treatment was an indication. CONCLUSION: Early preventive tracheostomy during TORS can protect airway from uncommon but potentially life-threatening complications, such as transoral hemorrhage or airway edema. We recommend it in high-risk situations, such as a past history of radiotherapy or antiplatelet therapy associated with large resections. Further studies are needed to establish evidence-based recommendations.

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.

Functional outcomes of soft palate free flap reconstruction following oropharyngeal cancer surgery.

INTRODUCTION: The objective of this study was to assess the impact of surgical resection and free flap reconstruction of soft palate cancer on speech, swallowing and quality of life, and to identify the factors influencing functional outcomes and quality of life. MATERIAL AND METHODS: Patients treated with surgical resection of squamous cell carcinoma and free-flap reconstruction of the soft palate were reviewed at least 12 months after surgery. Speech was assessed using the Hirose intelligibility scoring system, nasalance scoring, GRBAS scoring and the Voice Handicap Index 30 (VHI30) questionnaire. Swallowing was assessed by fiberoptic endoscopy and the Deglutition Handicap Index (DHI). Quality of life was assessed using EORTC QLQ-C30 and QLQ-H&N35 questionnaires. RESULTS: 29 patients were included. Speech outcomes were satisfactory, demonstrating normal or slightly below normal speech intelligibility in 75.9% of the patients, moderate or no rhinolalia in 72.4% of the patients and mean overall VHI30 scores indicative of slight or no handicap in 86.2% of the patients. Swallowing outcomes were satisfactory, with mean overall DHI scores indicative of slight or no handicap in 82.8% of the patients. Patient quality of life was preserved as demonstrated by mean quality of life and functioning scales scores all superior to 80%. CONCLUSION: The sequelae arising from surgical resection and free-flap reconstruction of soft palate cancer are tolerable, involving slight handicap in terms of speech and swallowing and relatively little impact on quality of life.

History of tonsillectomy and risk of oropharyngeal cancer.

OBJECTIVE: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). MATERIALS AND METHODS: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference. RESULTS: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results. CONCLUSION: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.

Influence of postoperative radiotherapy target volumes in unilateral head and neck carcinoma of unknown primary: A multicentric study using propensity score.

OBJECTIVE: To compare the impact of two radiation modalities on loco-regional control, survival and tumour emergence, after node dissection for an unilateral head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: This is a multicentric retrospective study of 138 patients with unilateral HNCUP treated between 2002 and 2017. The absence of primary tumour was assessed by a systematic panendoscopy and positron emission tomography. Neck dissection was initially performed for all patients. Radiation Therapy was delivered on ipsilateral lymph node areas in 62 cases (44%: UL-RT group) and on bilateral lymph node areas and the entire pharyngeal mucosa in 77 cases (56%: COMP-RT group). Impact of radiation modalities on locoregional control and overall survival was assessed using propensity score matching method in order to balance baseline characteristics between the two groups. RESULTS: The population included 80.4% men, 80.4% smokers, 32.6% P16 positive tumours and 71.0% extracapsular extension. After a median follow-up of 5 years, the locoregional control rate was 80.3% in the UL-RT group and 75.3% in the COMP-RT group (p = 0.688). The corresponding rate of contralateral lymph node recurrence was 0% versus 2.6% (p = 0.503) and the rate of tumour emergence was 11.5% versus 9.1% (p = 0.778). No significant difference was observed between the UL-RT and the COMP-RT groups for overall survival (p = 0.9516), specific survival (p = 0.4837) or tumour emergence (p = 0.9034). CONCLUSION: UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP post-operative management.

Zenker diverticulum treatment: retrospective comparison of flexible endoscopic window technique and surgical approaches.

INTRODUCTION: Different treatments exist for Zenker diverticulum. We compared flexible endoscopic myotomy of the cricopharyngeal muscle, using a technique called the "window technique" in order to improve the field of view, to surgical approaches. MATERIALS AND METHODS: Patients were retrospectively included and divided into a gastrointestinal group, with flexible endoscopic myotomy, and an ear-nose-throat treatments group with either rigid endoscopic treatment, either cervicotomy. We evaluated effectiveness in terms of quality of life (on a scale on 0 to 10) safety and technical aspects of each procedure. RESULTS: A total 106 patients who underwent 128 interventions were included. Rigid endoscopic procedures were the shortest (p < 0.001), with no difference for adverse event. Endoscopic approaches, flexible and rigid ones, were associated with shorter time to intake resumption (1 and 3 days, respectively, vs 6 after cervicotomy) and shorter length of hospital stay (3 and 4 days, respectively, vs 7 after cervicotomy) (p = 0.001). Post-operative QoL was better after flexible endoscopy (9/10) and open cervicotomy (9/10) than after rigid endoscopy (7/10) (p = 0.004). Patients declared fewer residual symptoms after open cervicotomy (77% of low symptomatic patients) and flexible endoscopy (80%) than after rigid endoscopy (43%) (p = 0.003). Conversion to open surgery was more frequent during rigid than flexible endoscopies (18% vs 0%, p = 0.0008). CONCLUSION: Flexible endoscopic approach of Zenker diverticulum treatment seems to be safe and effective and may be an alternative to surgical approaches. Myotomy can be eventually helped by the window technique.

Bilateral radical neck dissection with immediate reconstruction of the internal jugular vein.

Head and neck surgery for advanced neck disease may require ablation of critical structures, including the internal jugular vein (IJV). Although unilateral ligation of the IJV is not commonly associated with a significant increase in morbidity, bilateral sacrifice of the internal venous system may cause severe complications. We present the case of a 60-year-old man with a T4N2cM0 tumour of the left and right hypopharynx. The evolution of the disease required a bilateral modified radical neck dissection and sacrifice of both IJVs. We describe a vein grafting technique for the IJV using the external jugular vein as a donor vessel. Postoperative computed tomography imaging confirmed adequate blood perfusion. This report describes two new and accessible surgical options for immediate IJV grafting. Although this modification slightly increases the surgery time and technical difficulty, it allows immediate restoration of venous perfusion, which may improve the prognosis and patient outcomes.

Oral and oropharyngeal cancer surgery with free-flap reconstruction in the elderly: Factors associated with long-term quality of life, patient needs and concerns. A GETTEC cross-sectional study.

OBJECTIVES: To assess the factors associated with long-term quality of life (QoL) and patient concerns in elderly oral or oropharyngeal cancer (OOPC) patients after oncologic surgery and free-flap reconstruction. METHODS: Patients aged over 70 years who were still alive and disease-free at least 1 year after surgery were enrolled in this cross-sectional multicentric study. Patients completed the EORTC QLQ-C30, -H&N35 and -ELD14 QoL questionnaires, and the Hospital Anxiety and Depression Scale (HADS). Patient needs were evaluated using the Patient Concerns Inventory (PCI). Factors associated with these clinical outcomes were determined in univariate and multivariate analysis. RESULTS: Sixty-four patients were included in this study. Long-term QoL, functioning scales and patient autonomy were well-preserved. Main persistent symptoms were fatigue, constipation and oral function-related disorders. Salivary and mastication/swallowing problems were the main patient concerns. The mean number of patient concerns increased with the deterioration of their QoL. Psychological distress (HADS score ≥ 15) and patient frailty (G8 score < 15) were significantly associated with poor QoL outcomes. CONCLUSIONS: We found a negative correlation between the number of patient concerns and QoL. Dental rehabilitation and psychological and nutritional supportive measures are of critical importance in the multidisciplinary management of elderly OOPC patients.

Hyperprogression and impact of tumor growth kinetics after PD1/PDL1 inhibition in head and neck squamous cell carcinoma.

Background: Hyperprogressive disease (HPD) rate in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI) was determined using tumor growth kinetics (TGK) and compared with rapidly progressive screen-failure (SF) patients. The impact of TGK on outcomes with salvage chemotherapy (SCT) was also evaluated. Results: HPD was found in 22/120 (18%) patients. Median TGK before the onset of immunotherapy (TGKpre) was 2.7 for SF patients and 4.8 for HPD patients, with no significant difference (p = 0.17). Disease control rate after initial progressive disease on ICI was 86% with SCT in case of tumor growth deceleration vs 39% in case of tumor growth acceleration. Conclusions: HPD was frequent, but TGK of HPD patients treated with ICI did not differ from SF patients, suggesting that there is no relevant causal relationship between HPD and ICI. After initial PD with ICI, tumor growth deceleration was associated with better outcomes, indicating that TGKR might be useful to detect late responders, meriting prospective investigations. Materials and Methods: TGK ratio (TGKR) was defined as the ratio of TGK on ICI (TGKpost) to TGKpre. HPD was defined as TGKR ≥ 2. TGKR >1 indicated tumor growth acceleration, while 0 < TGKR < 1 indicated tumor deceleration.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. METHODS AND MATERIALS: Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 µg (n = 56), 100 µg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). RESULTS: SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. CONCLUSIONS: Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

Evaluation of virtual surgical planning systems and customized devices in fibula free flap mandibular reconstruction.

PURPOSE: The purpose of this study was to evaluate the accuracy of virtual planning using customized surgical devices (VP3D) in fibula free flap mandibular reconstruction. METHODS: Fourteen patients received VP3D and 16 patients underwent conventional surgery (CS). Virtual planning was compared to postoperative scans using cephalometric and three-dimensional (3D) measurements. Operative times of both VP3D and CS groups were compared. RESULTS: Comparisons of cephalometric measurements revealed no significant difference between virtual planning and postoperative scans. 3D analysis demonstrated a high level of virtual planning accuracy. In the VP3D group, total operative time gain was 88 min (p < 0.001) and total ischemia time gain was 36 min (p = 0.04). CONCLUSION: Virtual surgical planning using customized devices enables 'tailored' surgery that is accurate and reliable and results in operative and ischemia time gain. CLINICAL TRIAL: NCT03869723.