Diverse alterations associated with resistance to KRAS(G12C) inhibition.

Inactive state-selective KRAS(G12C) inhibitors1-8 demonstrate a 30-40% response rate and result in approximately 6-month median progression-free survival in patients with lung cancer9. The genetic basis for resistance to these first-in-class mutant GTPase inhibitors remains under investigation. Here we evaluated matched pre-treatment and post-treatment specimens from 43 patients treated with the KRAS(G12C) inhibitor sotorasib. Multiple treatment-emergent alterations were observed across 27 patients, including alterations in KRAS, NRAS, BRAF, EGFR, FGFR2, MYC and other genes. In preclinical patient-derived xenograft and cell line models, resistance to KRAS(G12C) inhibition was associated with low allele frequency hotspot mutations in KRAS(G12V or G13D), NRAS(Q61K or G13R), MRAS(Q71R) and/or BRAF(G596R), mirroring observations in patients. Single-cell sequencing in an isogenic lineage identified secondary RAS and/or BRAF mutations in the same cells as KRAS(G12C), where they bypassed inhibition without affecting target inactivation. Genetic or pharmacological targeting of ERK signalling intermediates enhanced the antiproliferative effect of G12C inhibitor treatment in models with acquired RAS or BRAF mutations. Our study thus suggests a heterogenous pattern of resistance with multiple subclonal events emerging during G12C inhibitor treatment. A subset of patients in our cohort acquired oncogenic KRAS, NRAS or BRAF mutations, and resistance in this setting may be delayed by co-targeting of ERK signalling intermediates. These findings merit broader evaluation in prospective clinical trials.

Comprehensive transcriptome-wide analysis of spliceopathy correction of myotonic dystrophy using CRISPR-Cas9 in iPSCs-derived cardiomyocytes.

CTG repeat expansion (CTGexp) is associated with aberrant alternate splicing that contributes to cardiac dysfunction in myotonic dystrophy type 1 (DM1). Excision of this CTGexp repeat using CRISPR-Cas resulted in the disappearance of punctate ribonuclear foci in cardiomyocyte-like cells derived from DM1-induced pluripotent stem cells (iPSCs). This was associated with correction of the underlying spliceopathy as determined by RNA sequencing and alternate splicing analysis. Certain genes were of particular interest due to their role in cardiac development, maturation, and function (TPM4, CYP2J2, DMD, MBNL3, CACNA1H, ROCK2, ACTB) or their association with splicing (SMN2, GCFC2, MBNL3). Moreover, while comparing isogenic CRISPR-Cas9-corrected versus non-corrected DM1 cardiomyocytes, a prominent difference in the splicing pattern for a number of candidate genes was apparent pertaining to genes that are associated with cardiac function (TNNT, TNNT2, TTN, TPM1, SYNE1, CACNA1A, MTMR1, NEBL, TPM1), cellular signaling (NCOR2, CLIP1, LRRFIP2, CLASP1, CAMK2G), and other DM1-related genes (i.e., NUMA1, MBNL2, LDB3) in addition to the disease-causing DMPK gene itself. Subsequent validation using a selected gene subset, including MBNL1, MBNL2, INSR, ADD3, and CRTC2, further confirmed correction of the spliceopathy following CTGexp repeat excision. To our knowledge, the present study provides the first comprehensive unbiased transcriptome-wide analysis of the differential splicing landscape in DM1 patient-derived cardiac cells after excision of the CTGexp repeat using CRISPR-Cas9, showing reversal of the abnormal cardiac spliceopathy in DM1.

Using the Patient Health Questionnaire-2 to improve depression screening in head and neck cancer patients.

PURPOSE: The purpose of this study is to examine the use of the Patient Health Questionnaire-2 (PHQ-2) to screen for depression in patients undergoing treatment for head and neck cancer and to evaluate potential patient-specific risk factors that may contribute to depression. MATERIALS AND METHODS: This is a retrospective study at a tertiary-level hospital of outpatient adult patients with head and neck cancer who completed the PHQ-2/9 from 2019 to 2020. Patients were given a PHQ-2 during a surveillance visit. A positive PHQ-2 screen (score ≥ 3) prompted further evaluation with a PHQ-9. Patients were stratified into either low risk (PHQ-2 score < 3) or high risk (PHQ-2 score ≥ 3) for depression. Univariate regression was performed on all variables, and a multivariate logistic regression was performed on statistically significant variables (P < 0.05). RESULTS: In total, 110 patients were included in this study. Fifteen (14 %) patients had a positive PHQ-2 screen with a score ≥ 3 and underwent evaluation with a PHQ-9. The median PHQ-9 score was 15 (6-26). The PHQ-2 ≥ 3 group were significantly younger (59 years vs. 67 years; P = 0.03) and had a greater number of patients with a psychiatric history (33 % vs. 8 %; P < 0.01). CONCLUSIONS: There is a strong association between a PHQ-2 score ≥ 3 and detection of depressive symptoms among patients with head and neck cancer. Younger age and pretreatment mental illness are significant risk factors for developing depression following treatment. Early screening and treatment should be considered for all patients to mitigate the burden of depression and suicide in this patient population. Further research is warranted to investigate utilization of the PHQ-2/9 to detect depression and barriers that exist for timely screening and interventions.

The clinical behavior and genomic features of the so-called adenoid cystic carcinomas of the solid variant with basaloid features.

Classic adenoid cystic carcinomas (C-AdCCs) of the breast are rare, relatively indolent forms of triple negative cancers, characterized by recurrent MYB or MYBL1 genetic alterations. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a rare variant of AdCC yet to be fully characterized. Here, we sought to determine the clinical behavior and repertoire of genetic alterations of SB-AdCCs. Clinicopathologic data were collected on a cohort of 104 breast AdCCs (75 C-AdCCs and 29 SB-AdCCs). MYB expression was assessed by immunohistochemistry and MYB-NFIB and MYBL1 gene rearrangements were investigated by fluorescent in-situ hybridization. AdCCs lacking MYB/MYBL1 rearrangements were subjected to RNA-sequencing. Targeted sequencing data were available for 9 cases. The invasive disease-free survival (IDFS) and overall survival (OS) were assessed in C-AdCC and SB-AdCC. SB-AdCCs have higher histologic grade, and more frequent nodal and distant metastases than C-AdCCs. MYB/MYBL1 rearrangements were significantly less frequent in SB-AdCC than C-AdCC (3/14, 21% vs 17/20, 85% P < 0.05), despite the frequent MYB expression (9/14, 64%). In SB-AdCCs lacking MYB rearrangements, CREBBP, KMT2C, and NOTCH1 alterations were observed in 2 of 4 cases. SB-AdCCs displayed a shorter IDFS than C-AdCCs (46.5 vs 151.8 months, respectively, P < 0.001), independent of stage. In summary, SB-AdCCs are a molecularly heterogeneous but clinically aggressive group of tumors. Less than 25% of SB-AdCCs display the genomic features of C-AdCC. Defining whether these tumors represent a single entity or a collection of different cancer types with a similar basaloid histologic appearance is warranted.

Total laryngectomy negatively impacts sinonasal and olfactory-specific quality of life.

PURPOSE: The purpose of this study is to characterize deficits in olfactory-specific and sinonasal-specific QoL after total laryngectomy (TL) with validated patient reported outcome measures. METHODS: Thirty patients who had a TL were prospectively enrolled. Patient demographics, as well as scores from the Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and the Sino-nasal Outcome Test-22 (SNOT-22) were collected. Univariate analysis was performed to assess associations between patient characteristics and QoL scores. RESULTS: The average QOD-NS score was 37.9 ± 11.4 (<38.5 is considered abnormal) and average SNOT-22 score was 32.0 ± 3.8 (>20 indicates a moderate/severe impact on QoL). The abnormal QOD-NS group had a greater percentage of former smokers compared to the normal group (77.8% vs. 58.1%; P = 0.56) and more median days from surgery compared to the normal group (904 vs. 477 days; P = 0.24). CONCLUSIONS: Olfactory dysfunction associated with TL results in blunting of olfactory-specific QoL.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

BACKGROUND: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. METHODS: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. RESULTS: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). CONCLUSIONS: With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in the Muscle of DM1 Mice.

Myotonic dystrophy type 1 (DM1) is caused by a CTG repeat expansion located in the 3' UTR of the DMPK gene. Expanded DMPK transcripts aggregate into nuclear foci and alter the function of RNA-binding proteins, leading to defects in the alternative splicing of numerous pre-mRNAs. To date, there is no curative treatment for DM1. Here we investigated a gene-editing strategy using the CRISPR-Cas9 system from Staphylococcus aureus (Sa) to delete the CTG repeats in the human DMPK locus. Co-expression of SaCas9 and selected pairs of single-guide RNAs (sgRNAs) in cultured DM1 patient-derived muscle line cells carrying 2,600 CTG repeats resulted in targeted DNA deletion, ribonucleoprotein foci disappearance, and correction of splicing abnormalities in various transcripts. Furthermore, a single intramuscular injection of recombinant AAV vectors expressing CRISPR-SaCas9 components in the tibialis anterior muscle of DMSXL (myotonic dystrophy mouse line carrying the human DMPK gene with >1,000 CTG repeats) mice decreased the number of pathological RNA foci in myonuclei. These results establish the proof of concept that genome editing of a large trinucleotide expansion is feasible in muscle and may represent a useful strategy to be further developed for the treatment of myotonic dystrophy.

Efficient CRISPR/Cas9-mediated editing of trinucleotide repeat expansion in myotonic dystrophy patient-derived iPS and myogenic cells.

CRISPR/Cas9 is an attractive platform to potentially correct dominant genetic diseases by gene editing with unprecedented precision. In the current proof-of-principle study, we explored the use of CRISPR/Cas9 for gene-editing in myotonic dystrophy type-1 (DM1), an autosomal-dominant muscle disorder, by excising the CTG-repeat expansion in the 3'-untranslated-region (UTR) of the human myotonic dystrophy protein kinase (DMPK) gene in DM1 patient-specific induced pluripotent stem cells (DM1-iPSC), DM1-iPSC-derived myogenic cells and DM1 patient-specific myoblasts. To eliminate the pathogenic gain-of-function mutant DMPK transcript, we designed a dual guide RNA based strategy that excises the CTG-repeat expansion with high efficiency, as confirmed by Southern blot and single molecule real-time (SMRT) sequencing. Correction efficiencies up to 90% could be attained in DM1-iPSC as confirmed at the clonal level, following ribonucleoprotein (RNP) transfection of CRISPR/Cas9 components without the need for selective enrichment. Expanded CTG repeat excision resulted in the disappearance of ribonuclear foci, a quintessential cellular phenotype of DM1, in the corrected DM1-iPSC, DM1-iPSC-derived myogenic cells and DM1 myoblasts. Consequently, the normal intracellular localization of the muscleblind-like splicing regulator 1 (MBNL1) was restored, resulting in the normalization of splicing pattern of SERCA1. This study validates the use of CRISPR/Cas9 for gene editing of repeat expansions.

New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats.

Myotonic Dystrophy type I (DM1) is caused by an abnormal expansion of CTG triplets in the 3' UTR of the dystrophia myotonica protein kinase (DMPK) gene, leading to the aggregation of the mutant transcript in nuclear RNA foci. The expanded mutant transcript promotes the sequestration of the MBNL1 splicing factor, resulting in the misregulation of a subset of alternative splicing events. In this study, we identify the DEAD-box RNA helicase p68 (DDX5) in complexes assembled onto in vitro-transcribed CUG repeats. We showed that p68 colocalized with RNA foci in cells expressing the 3'UTR of the DMPK gene containing expanded CTG repeats. We found that p68 increased MBNL1 binding onto pathological repeats and the stem-loop structure regulatory element within the cardiac Troponin T (TNNT2) pre-mRNA, splicing of which is misregulated in DM1. Mutations in the helicase core of p68 prevented both the stimulatory effect of the protein on MBNL1 binding and the colocalization of p68 with CUG repeats, suggesting that remodeling of RNA secondary structure by p68 facilitates MBNL1 binding. We also found that the competence of p68 for regulating TNNT2 exon 5 inclusion depended on the integrity of MBNL1 binding sites. We propose that p68 acts as a modifier of MBNL1 activity on splicing targets and pathogenic RNA.

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study.

BACKGROUND: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. OBJECTIVE: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. METHODS: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. CONCLUSIONS: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

Early Detection of Lymph Node Metastasis Using Primary Head and Neck Cancer Computed Tomography and Fluorescence Lifetime Imaging.

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions: Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Stratification of surgical margin distances by the millimeter on local recurrence in oral cavity cancer: A systematic review and meta-analysis.

There are limited data supporting the commonly suggested 5 mm margin cutoff as the optimum value in defining clear margins in oral cancer. A database search of Pubmed/Medline, Web of Science, and EBSCOhost was performed from inception to June 2022. A random-effects model was chosen for this meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed throughout this study. Seven studies met study criteria (2215 patients). The risk ratio was significantly higher for margins <5 mm when compared to those ≥5 mm (2.09 (95%CI: 1.53-2.86, I2  = 0.47)). Subgroup analysis (I2  = 0.15) of margin distances of 0.0-0.9, 1.0-1.9, 2.0-2.9, 3.0-3.9, and 4.0-4.9 mm calculated risk ratios for local recurrence of 2.96, 2.01, 2.17, 1.8, and 0.98, respectively. Margins between 4.0 and 4.9 mm had similar risk ratios for local recurrence compared to ≥5 mm, while margins <4.0 were significantly higher.

Virtual Tumor Boards for Remote Learning in Head and Neck Surgical Oncology.

Importance: In addition to their patient management value, multidisciplinary tumor boards have been recognized as effective learning tools. However, the value of using a virtual tumor board as a learning tool for head and neck surgical oncology fellows has not been studied. Objective: To describe the structure and content of the American Head and Neck Society (AHNS) Virtual Tumor Board and assess its educational value as perceived by attendees. Design, Setting, and Participants: All sessions of the AHNS Virtual Tumor Board from April 8, 2020, to June 1, 2022, were reviewed. Topics, presenters, participants, and viewership data were collected as of October 15, 2022, from session recordings posted to an online video sharing and social media platform. Additionally, an anonymous, 14-question online survey was designed to elicit feedback from head and neck surgery trainees on virtual tumor board engagement, strengths, and weaknesses. The survey was electronically distributed in June and July 2022 to the 101 fellows enrolled in AHNS-accredited programs between July 1, 2020, and June 30, 2022. Main Outcomes and Measures: The primary aim was to tabulate online viewership of the sessions. The secondary aim was to qualitatively assess the experience of head and neck trainees with the AHNS Virtual Tumor Board using a survey. Results: Forty-two sessions of the virtual tumor board were held between April 8, 2020, and June 1, 2022. Almost all sessions (41 [98%]) were case based. One hundred and sixteen cases were presented, representing 2 to 3 cases per session, by 75 unique faculty members. Each session was viewed a mean of 217 times (range, 64-2216 views). In the 2021 to 2022 academic year, a mean of 60 viewers (range, 30-92 viewers) attended each live session. In all, 29 survey responses were collected from 101 fellows in AHNS-accredited programs (29% response rate). Most respondents felt the format allowed for excellent teaching (18 of 26 respondents [69%]) and discussion (19 of 26 respondents [73%]). Most respondents (22 of 29 respondents [76%]) believed that practicing head and neck surgeons would benefit from the sessions. Conclusions and Relevance: This survey study found that the AHNS Virtual Tumor Board was well-attended and well-reviewed by head and neck surgical oncology trainees. The virtual tumor board format could be used as model of remote learning for other organizations.

Predictors of Health Care Utilization Following Major Head and Neck Oncologic Surgery in Older Patients.

OBJECTIVE: To identify patient factors in older patients associated with making posttreatment visits in the first year after major head and neck oncologic surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: Patients aged ≥60 years who underwent a neck dissection with or without a free flap reconstruction were retrospectively analyzed. Data collected included patient demographics, comorbidities, social variables, perioperative course, and clinical visits. RESULTS: Within a 1-year postoperative period, the 181 patients in our cohort had a mean ± SD 6.37 ± 3.6 postoperative clinic visits; 70% attended at least 4 visits. Multivariable regression analysis showed a significant association with distance closer to the hospital (P = .013): for every 10-mile increase in distance, the number of visits decreased by 0.15 (SE = 0.06). Additionally, receiving adjuvant radiation therapy (P = .0096) demonstrated significant associations: when compared with no adjuvant therapy, radiation therapy had on average 1.5 (SE = 0.56) more visits, and chemoradiation had 0.04 (SE = 0.73) more visits. CONCLUSION: Older patients who undergo major head and neck oncology surgery are more likely to attend posttreatment visits in the 1 year following surgery if they are discharged home rather than to a skilled nursing facility, live closer to the hospital, and undergo adjuvant radiation therapy.

Tumor and Nodal Disease Growth Rates in Patients with Oropharyngeal Squamous Cell Carcinoma.

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012-2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

Anatomy-Specific Classification Model Using Label-Free FLIm to Aid Intraoperative Surgical Guidance of Head and Neck Cancer.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Potential of the predatory mite, Amblyseius swirskii to suppress the broad mite, Polyphagotarsonemus latus on the gboma eggplant, Solanum macrocarpon.

In Benin, the tarsonemid mite Polyphagotarsonemus latus (Banks) (Prostigmata: Tarsonemidae) is a key pest of gboma eggplant Solanum macrocarpon (L.) (Solanales: Solanaceae), a leafy vegetable on which it causes considerable damage to the plants and substantial reduction in yield. Predatory mites in the family Phytoseiidae have been successfully used in the biological control of numerous agricultural pests worldwide. In that respect, a population of the phytoseiid mite Amblyseius swirskii (Athias-Henriot) (Mesostigmata: Phytoseiidae) has been identified as a potential predator of P. latus, and is now a candidate for release against this pest in Benin. The objective of the present study is to determine, through laboratory experiments, the predation rate and life table parameters of A. swirskii when feeding on P. latus or alternative food such as maize pollen. Under laboratory conditions the mean number of P. latus consumed by A. swirskii, and daily oviposition, significantly increased as the number of prey increased. Total development time of A. swirskii was significantly shorter when it fed on P. latus than on maize pollen. Net reproduction rate, intrinsic rate of increase, mean generation time and the finite rate of increase of A. swirskii were were all significantly lower on P. latus than on maize pollen. However, doubling time was significantly higher on maize pollen. This study shows that A. swirskii is a good predator of P. latus, and that maize pollen can efficiently sustain A. swirskii populations when P. latus densities on plants become low. Consequently, A. swirskii can be used for the biological control of the broad mite P. latus on gboma eggplant, and on other solanaceous crops in Benin and elsewhere.

Gadolinium enhancement in brain magnetic resonance imaging in progressive multifocal leukoencephalopathy after natalizumab monotherapy: is it really atypical?

Progressive multifocal leukoencephalopathy (PML) generally occurs in patients with impaired cellular immunity. Monoclonal antibodies also predispose the patient to PML as they depress the immune system. PML was classically characterized by a lack of inflammation and absence of gadolinium enhancement. However, gadolinium enhancement of PML lesions was first described in HIV-positive patients under therapy. We present a case of gadolinium enhanced PML lesions occuring after natalizumab monotherapy of a relapsing multiple sclerosis. Radiologists must be aware of this particular feature, as confirmation of the diagnostic of PML becomes more challenging. Namely, distinction between starting PML and multiple sclerosis enhanced additional active lesion is difficult and diagnosis must be established by combined analysis of full clinical evolution, brain MRI scans, and polymerase chain reaction of cerebrospinal fluid.

Oropharyngeal reconstruction after transoral robotic surgery.

PURPOSE OF REVIEW: Transoral robotic surgery (TORS) has experienced an evolution in recent years. This technique has proved to be a safe and effective method for extirpation of select oropharyngeal tumors. Advances in technology as well as improved surgeon experience allow for the resection of larger, more complex cancers. Although healing by secondary intention remains the current standard for limited oropharyngeal defects, larger resections demand reconstruction with vascularized tissue to minimize morbidity and optimize functional outcomes. The objective of this review is to evaluate recent literature regarding oropharyngeal reconstruction after TORS. RECENT FINDINGS: A variety of reconstructive options to manage oropharyngeal defects exist. Several reconstructive algorithms have been suggested; however, careful consideration must be used to select the most ideal flap type. Locoregional flaps have shown excellent functional outcomes with limited morbidity. An increase in free flap reconstruction has been demonstrated, particularly among patients with larger TORS defects and following chemoradiation therapy. Despite limited data, robotic-assisted flap inset and microvascular anastomosis has recently shown promise. SUMMARY: Reconstruction and flap selection following TORS should be tailored to the patient and unique oropharyngeal defect. Functional outcomes are promising with low complication rates among these patients.