Multi-planar dual adversarial network based on dynamic 3D features for MRI-CT head and neck image synthesis.

Objective.Head and neck radiotherapy planning requires electron densities from different tissues for dose calculation. Dose calculation from imaging modalities such as MRI remains an unsolved problem since this imaging modality does not provide information about the density of electrons.Approach.We propose a generative adversarial network (GAN) approach that synthesizes CT (sCT) images from T1-weighted MRI acquisitions in head and neck cancer patients. Our contribution is to exploit new features that are relevant for improving multimodal image synthesis, and thus improving the quality of the generated CT images. More precisely, we propose a Dual branch generator based on the U-Net architecture and on an augmented multi-planar branch. The augmented branch learns specific 3D dynamic features, which describe the dynamic image shape variations and are extracted from different view-points of the volumetric input MRI. The architecture of the proposed model relies on an end-to-end convolutional U-Net embedding network.Results.The proposed model achieves a mean absolute error (MAE) of18.76±5.167in the target Hounsfield unit (HU) space on sagittal head and neck patients, with a mean structural similarity (MSSIM) of0.95±0.09and a Frechet inception distance (FID) of145.60±8.38. The model yields a MAE of26.83±8.27to generate specific primary tumor regions on axial patient acquisitions, with a Dice score of0.73±0.06and a FID distance equal to122.58±7.55. The improvement of our model over other state-of-the-art GAN approaches is of 3.8%, on a tumor test set. On both sagittal and axial acquisitions, the model yields the best peak signal-to-noise ratio of27.89±2.22and26.08±2.95to synthesize MRI from CT input.Significance.The proposed model synthesizes both sagittal and axial CT tumor images, used for radiotherapy treatment planning in head and neck cancer cases. The performance analysis across different imaging metrics and under different evaluation strategies demonstrates the effectiveness of our dual CT synthesis model to produce high quality sCT images compared to other state-of-the-art approaches. Our model could improve clinical tumor analysis, in which a further clinical validation remains to be explored.

PET-CT-guided, symptom-based, patient-initiated surveillance versus clinical follow-up in head neck cancer patients (PETNECK2): study protocol for a multicentre feasibility study and non-inferiority, randomised, phase III trial.

BACKGROUND: Approximately 40% of treated head and neck cancer (HNC) patients develop recurrence. The risk of recurrence declines with time from treatment. Current guidelines recommend clinical follow-up every two months for the first two years after treatment, with reducing intensity over the next three years. However, evidence for the effectiveness of these regimes in detecting recurrence is lacking, with calls for more flexible, patient-centred follow-up strategies. METHODS: PETNECK2 is a UK-based multi-centre programme examining a new paradigm of follow-up, using positron emission tomography-computed tomography (PET-CT)-guided, symptom-based, patient-initiated surveillance. This paradigm is being tested in a unblinded, non-inferiority, phase III, randomised controlled trial (RCT). Patients with HNC, one year after completing curative intent treatment, with no clinical symptoms or signs of loco-regional or distant metastasis will be randomised using a 1:1 allocation ratio to either regular scheduled follow-up, or to PET-CT guided, patient-initiated follow-up. Patients at a low risk of recurrence (negative PET-CT) will receive a face-to-face education session along with an Information and Support (I&S) resource package to monitor symptoms and be in control of initiating an urgent appointment when required. The primary outcome of the RCT is overall survival. The RCT also has an in-built pilot, a nested QuinteT Recruitment Intervention (QRI), and a nested mixed-methods study on patient experience and fear of cancer recurrence (FCR). An initial, single-arm feasibility study has been completed which determined the acceptability of the patient-initiated surveillance intervention, the completion rates of baseline questionnaires, and optimised the I&S resource prior to implementation in the RCT. DISCUSSION: We hypothesise that combining an additional 12-month post-treatment PET-CT scan and I&S resource will both identify patients with asymptomatic recurrence and identify those at low risk of future recurrence who will be empowered to monitor their symptoms and seek early clinical follow-up when recurrence is suspected. This change to a patient-centred model of care may have effects on both quality of life and fear of cancer recurrence. TRIAL REGISTRATION: ISRCTN: 13,709,798; 15-Oct-2021.

Differential Immune Checkpoint Protein Expression in HNSCC: The Role of HGF/MET Signaling.

Although inhibitors targeting the PD1/PD-L1 immune checkpoint are showing comparably good outcomes, a significant percentage of head and neck squamous cell carcinoma (HNSCC) patients do not respond to treatment. Apart from using different treatment strategies, another possibility would be to target other immune checkpoints operating in these non-responding tumors. To obtain an overview of which checkpoint ligands are expressed on HNSCC tumor cells and if these ligands are affected by HGF/MET signaling, we used mRNA sequencing and antibody-based techniques for identifying checkpoint ligands in six HNSCC tumor cell lines. Furthermore, we compared our results to mRNA sequencing data. From the checkpoint ligands we investigated, VISTA was expressed the highest at the RNA level and was also the most ubiquitously expressed. PD-L2 and B7-H3 were expressed comparably lower and were not present in all cell lines to the same extent. B7-H4, however, was only detectable in the Detroit 562 cell line. Concerning the effect of HGF on the ligand levels, PD-L2 expression was enhanced with HGF stimulation, whereas other checkpoint ligand levels decreased with stimulation. B7-H4 levels in the Detroit 562 cell line drastically decreased with HGF stimulation. This is of interest because both the checkpoint ligand and the growth factor are reported to be connected to epithelial-mesenchymal transition in the literature.

Intratumoral microbiome of adenoid cystic carcinomas and comparison with other head and neck cancers.

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.

Setting up a nurse-led 2-week-wait head and neck cancer diagnostic service.

The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.

Intramuscular injections of human placental extract versus conventional symptomatic approaches in radiation-induced oral mucositis, in patients with head and neck cancers, on definitive chemoradiotherapy - A ray of hope?

BACKGROUND: Despite the availability of a wide range of agents, no single treatment exists for the management of radiation-induced oral mucositis, in patients, with head and neck malignancies, on radical chemoradiation; a debilitating and limiting sequela. Human placental extract is one option that has been proposed. AIMS AND OBJECTIVES: This study aimed at evaluating the therapeutic benefits of human placental extract (Placentrex) in the management of radiation-induced oral mucositis in patients on curative intent treatment for head and neck cancers with concurrent chemoradiation, and to compare the observations with other conventional approaches. MATERIAL AND METHODS: Patients presenting to the Department of Radiation Oncology, of a tertiary cancer care center, with biopsy-proven carcinoma of the oral cavity, oropharynx, and hypopharynx, planned for definitive, curative intent chemoradiation, between January 2020 and June 2021, were recruited for this study. The interventional group received a deep intramuscular injection of 2 ml of Placentrex to the deltoid muscle, once-a-day from the 11th fraction of radiation till completion, on treatment and non-treatment days. The control group received supportive, symptomatic, conventional treatments for mucositis. The response was assessed every week during treatment and at the third and sixth months of follow-up and was compared. RESULTS: The study comprised 26 patients, 15 in the interventional group and 11 in the control group. On completion of treatment, 40% in the interventional arm and 81.82% in the control arm had progressed to grade 2 and 3 mucositis (P < 0.05). Treatment interruption was seen in 13% in the interventional arm and 55% in the control arm (P < 0.001). CONCLUSIONS: Results from this study show that human placental extract, injection Placentrex, had a significant effect in decreasing the severity of radiation-induced mucositis and thereby reducing any interruption or delay in treatment when compared to other conventional methods.

Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

AIM: The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. MATERIALS AND METHODS: ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. RESULTS: It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. CONCLUSION: The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

Diagnostic efficacy of dynamic contrast-enhanced magnetic resonance perfusion imaging in detecting local tumor recurrence in patients with head and neck malignancies after definitive treatment.

BACKGROUND AND AIM: Accurate interpretation of post-treatment imaging in head and neck malignancies poses a challenge due to treatment sequelae. Magnetic resonance (MR) perfusion helps in this scenario by evaluating the hemodynamic characteristics of lesions. This study aimed to elucidate the diagnostic efficacy of dynamic contrast-enhanced (DCE)-MR perfusion imaging in detecting recurrence in patients after they underwent definitive treatment for head and neck tumors. MATERIALS AND METHODS: Thirty patients who had received definitive curative-intent treatment for histopathology-proven malignant head and neck tumors and in whom recurrent tumor was detected on precontrast MR imaging (MRI) were accrued in the study. Patients underwent DCE-MR perfusion imaging. Time to peak (TTP), relative maximum enhancement (RME), and relative washout (RWO) ratio were calculated by using time-intensity curve (TIC). The diagnostic accuracy was compared with histopathology. RESULTS: A cut-off value of ≥125.3 for RME showed a sensitivity of 76.2% and specificity of 66.7% for differentiating post-radiation changes and recurrence. The optimal cut-off for RWO ratio was ≥-6.24 with a sensitivity of 76.2% and specificity of 55.6%. The optimal cut-off of TTP was ≤45.8 s with a sensitivity of 61.9% and specificity of 77.8%. Diagnostic accuracies of RME, RWO, and TTP were 73.3%, 70%, and 66.7%, respectively. CONCLUSIONS: DCE-MRI had significant diagnostic accuracy in detecting and differentiating recurrences. TIC analysis of high-temporal resolution DCE-MRI can provide information regarding microcirculation of tumors, and hence can be considered as an imaging modality of choice for assessment of early local tumor recurrence in head and neck tumors.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

BACKGROUND: Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. METHOD: Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. RESULT: Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. CONCLUSION: Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

p16, p53 and EGFR expression in head and neck squamous cell carcinoma and their correlation with clinicopathological parameters.

INTRODUCTION: Oral squamous cell carcinoma is a major cause of death throughout the developed world. Human papillomavirus (HPV) type 16 has also been suggested to play a role in etiology of head and neck squamous cell carcinoma (HNSCC). p16 expression is now being used as a surrogate marker of HPV infection in squamous cell carcinoma. Dysfunction in the p53 tumor suppressor gene is implicated in many cancers, including head and neck cancer. Overexpression or mutation of EGFR is found in 80%-100% of the patients with HNSCC, and is associated with poor prognosis and decreased survival. MATERIALS AND METHODS: In this cross-sectional observation study, total of 100 cases of HNSCC were taken. p16, p53, and EGFR expression was determined by immunohistochemical staining and correlated with clinicopathological parameters. p16 expression was also correlated with expression of p53 and EGFR. The obtained results were analyzed and evaluated using Chi-square test, value of P < 0.05 was taken significant. RESULTS: p16, p53, and EGFR were positive in 60%, 44%, and 58% cases, respectively. A statistically significant association was observed between p16 with age, site of the tumor, abnormal sexual habits and lymph node involvement. Significant expression also seen between p53 with age and abnormal sexual habits and immunohistochemical expression of p16 with p53 and EGFR. CONCLUSION: Immunohistochemical expression of p16 can be used as a surrogate marker of HPV. Study of p16, p53, and EGFR expression may provide clinicians with more exact information in order to evaluate tumor aggressiveness and treatment modalities.

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3.

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Tumor-associated genetic amplifications impact extracellular vesicle miRNA cargo and their recruitment of nerves in head and neck cancer.

Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between the nervous system, developing malignancies, and their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head and neck squamous cell carcinomas (HNSCCs) recruit loco-regional nerves to the tumor. sEVs contain a diverse collection of biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in HNSCC, CCND1, and PIK3CA, impact the sEV miRNA cargo and, subsequently, sEV-mediated tumor innervation. To test this, we individually overexpressed these genes in a syngeneic murine HNSCC cell line, purified their sEVs, and tested their neurite outgrowth activity on dorsal root ganglia (DRG) neurons in vitro. sEVs purified from Ccnd1-overexpressing cells significantly increased neurite outgrowth of DRG compared to sEVs from parental or Pik3ca over-expressing cells. When implanted into C57BL/6 mice, Ccnd1 over-expressing tumor cells promoted significantly more tumor innervation in vivo. qPCR analysis of sEVs shows that increased expression of Ccnd1 altered the packaging of miRNAs (miR-15-5p, miR-17-5p, and miR-21-5p), many of which target transcripts important in regulating axonogenesis. These data indicate that genetic amplifications harbored by malignancies impose changes in sEV miRNA cargo, which can influence tumorc innervation.

Management of large head and neck defects in the vessel-depleted neck.

PURPOSE OF REVIEW: Surgery, radiation, and chemotherapy are often utilized in the treatment of head and neck cancer. These treatments can cause extensive scarring within the neck and can limit the viability of recipient vessels for further microvascular reconstruction. Patients with vessel-depleted necks provide a significant challenge for microvascular surgeons and are a topic of much discussion in the field. RECENT FINDINGS: While reconstruction in the vessel-depleted neck is an active area of interest, the patient population is rare. Therefore, single institution series with small numbers comprise the majority of published literature. Recent publications describe techniques for identifying adequate recipient vessel options outside of the field of treatment with excellent free flap outcomes. Further, recent summary articles describe techniques for addressing issues with pedicle length that can arise when using vessels that are far from the defect to be reconstructed. SUMMARY: When viable vessel options are available within the treatment field, these recipient vessels can be used with good reliability and free flap success. If in-field recipient vessels are not available, minimal access incisions can be used to identify superficial temporal, angular, contralateral facial, or transverse cervical vessels. Further away from the treatment field, internal mammary vessels can be harvested through open or robotic approaches. If the use of these distant vessels creates issues with pedicle length, interposition vein grafts, arteriovenous (AV) loops, or flow-through flaps can be used to augment vessel length.

[Effectiveness and safety of multimodal analgesia in open gastrostomy in patients with end-stage head and neck cancer].

Objective: To investigate the effectiveness and safety of multimodal analgesia in patients with end-stage head and neck cancer in open gastrostomy surgery. Methods: This was a randomized controlled trial. From June to December 2023, 50 patients with end-stage head and neck cancer who underwent elective open gastrostomy surgery in Beijing Tongren Hospital Affiliated to Capital Medical University were prospectively selected. The patients were divided into multimodal analgesia group and local anesthesia group using the random number table method according to different anesthesia methods, with 25 cases in each group. In multimodal analgesia group, a multimodal analgesia regimen was adopted: ultrasound-guided abdominal wall nerve block (rectus sheath block and transverse abdominis plane block)+intravenous injection of oxycodone+intravenous injection of flurbiprofen axetil and dexamethasone. In local anesthesia group, local infiltration anesthesia with ropivacaine was adopted. The main outcome measure was the incidence of intraoperative pain numeric rating scale (NRS) score>3 points in the two groups. The secondary observation indicators included NRS score and hemodynamic indexes [mean arterial pressure (MAP) and heart rate (HR)] at various time points during surgery [before anesthesia (T0), at the time of incision (T1), 10 minutes after surgery (T2), during gastric body traction (T3), and at the end of surgery (T4)], incidence of adverse reactions, postoperative patient satisfaction score, as well as the NRS scores at rest and activity (coughing) within 24 hours after surgery. Results: The multimodal analgesia group included 21 males and 4 females, aged (61.4±9.9) years. There were 19 males and 6 females in the local anesthesia group, aged (58.6±10.8) years. The incidence of intraoperative NRS score>3 points and the incidence of salvage analgesia in the multimodal analgesia group were both 12.0% (3/25), which were lower than 60.0% (15/25) in the local anesthesia group, and the differences were statistically significant (all P<0.001); The NRS score [M (Q1, Q3)] at T3 in the multimodal analgesia group was 2 (2, 3) points, which were lower than 5 (3, 6) points in the local anesthesia group (P<0.05). There were smaller variabilities in MAP and HR in the multimodal analgesia group than those in the local anesthesia group (all P<0.05). The incidence of intraoperative tachycardia, surgical traction reaction, and nausea in the multimodal analgesia group was lower than that in the local anesthesia group (all P<0.05). The postoperative satisfaction score of patients in the multimodal analgesia group was (9.25±0.71) points, which were higher than (7.33±0.87) points in the local anesthesia group (P<0.001). NRS score during postoperative activity within 24 hours in the multimodal analgesia group were (2.36±0.75) points, which were lower than (3.03±0.81) points of the local anesthesia group (P=0.005). No adverse reactions such as urinary retention, nausea, vomiting and dizziness occurred in both groups. Conclusion: Compared with local anesthesia, the multimodal analgesic strategy could provide better analgesic effect and longer duration, better hemodynamic stability, and fewer intraoperative adverse reactions in patients with end-stage head and neck cancer undergoing open gastrostomy.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Anxiety symptoms predict head and neck cancer survival: Exploring mediation by systemic inflammation and tumor response to treatment.

BACKGROUND: Head and neck cancers (HNC) are associated with high rates of anxiety. Anxiety has been linked to biological pathways implicated in cancer progression, though little is known about its effects on overall survival. We hypothesized that higher pretreatment anxiety levels in patients with HNC would predict poorer 2-year overall survival and expected this relationship to be mediated by both systemic inflammation and tumor response to treatment. METHODS: Patients (N = 394) reported anxiety symptomatology via the GAD-7 at treatment planning. Pre-treatment hematology workup provided an index of systemic inflammation (SII; N = 292). Clinical data review yielded tumor response and overall survival. Logistic and multiple regressions and Cox proportional hazard models tested hypothesized relationships. RESULTS: Higher pretreatment anxiety levels were significantly associated with poorer 2-year survival (hazard ratio [HR], 1.039; 95% confidence interval [CI], 1.014-1.066, p = 0.002). The association between anxiety and SII was not significant, though anxiety was associated with poorer tumor response (odds ratio [OR], 1.033; 95% CI, 1.001-1.066, p = 0.043). Tumor response fully mediated the relationship between anxiety symptoms and 2-year survival (HR, 9.290, 95% CI, 6.152-14.031, p < 0.001). CONCLUSIONS: Anxiety was associated with overall survival. Tumor response, but not systemic inflammation, emerged as a potential biological pathway mediating this effect. Screening for anxiety may be beneficial to help prospectively address these concerns and ameliorate potentially detrimental impact on clinically meaningful cancer outcomes.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.