Long-term outcomes and prognosis of neuroendocrine neoplasms of the head and neck: a cohort from a single institution.

BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.

Femoral shaft displacement and Winquist classification provide predictive characteristics for combined femoral neck and femoral shaft fractures.

OBJECTIVES: The goal of this study is to establish radiographic features and characteristics of patient injury in cases of femoral shaft fractures that predict the presence of ipsilateral femoral neck fractures (IFNFs). METHODS: Patient data was retrospectively assessed from a single level I trauma center through the electronic health record using (Current Procedural Terminology) CPT codes for both isolated and combined ipsilateral femoral shaft and neck fractures. Demographic information, injury characteristics, and independently reviewed radiographic features were collected and compared against the same information from a group of isolated femoral shaft fractures. Multivariable logistic regression was performed to identify risk factors for concomitant IFNFs and their respective odds ratios. A probability algorithm for assessing ipsilateral femoral neck fractures based on independent multivariate predictors was constructed and used. RESULTS: A total of 113 patients with either isolated femoral shaft fractures or combined femoral shaft and IFNF (n = 33) met inclusion criteria and were identified for this study. Fracture displacement was most strongly associated with increased risk of combined injury with an aOR of 25.64 (95 %CI = 5.96-110.28) for every 100 % displacement. Motorcycle crash (MCC) was the mechanism associated with the highest risk of combined injury, with an aOR of 9.85 (95 % CI = 1.99-48.74). Combined injury was also correlated with lower Winquist score and presentation with a closed fracture, with aORs of 0.38 (95 %CI = 0.21 - 0.68) and 11.61 (95 %CI = 1.93-69.94), respectively. Presence of at least 3 of the statistically significant variables produced a positive predictive value (PPV) of ≥ 89 % for combined femoral shaft and IFNF. CONCLUSIONS: Identification of combined femoral shaft and IFNF is of critical importance when caring for orthopedic trauma patients. While diagnosis remains a challenging task, MCC mechanism, >100 % fracture displacement, and lower Winquist classification were found to be associated with combined injuries. The combination of these variables might assist in predicting the probability of combined injury and potentially guide decision making on the appropriateness of obtaining single sequence MRI or implementing prophylactic femoral neck fixation. LEVEL OF EVIDENCE: Level III.

Biomechanical evaluation of a central collinear entry reconstruction nail for femoral neck fracture prophylaxis.

INTRODUCTION: Reconstruction nails are commonly used to treat proximal femur fractures, with cephalic screw placement for femoral neck "prophylaxis" becoming standard practice. These implants are traditionally introduced through piriformis fossa (PF) or greater trochanter (GT) entry portals. A third "central collinear" (CC) portal has been proposed that allows entry along the femoral anatomic axis and central placement of cephalic screws. The present study aimed to quantify and compare the CC portal femoral neck strength with the two traditional (PF and GT) entry portals. MATERIALS AND METHODS: Eighteen cadaveric femur specimens (nine matched pairs) were divided into three groups using a balanced incomplete block design to control for variations in age and sex: (1) GT, (2) CC, and (3) PF entry points. Specimens and implants were cut to a standard length and instrumented with straight or valgus bend nails of appropriate laterality and two cephalic screws. Specimens were mounted on a custom jig replicating load distribution along the mechanical axis. A 100 N compressive preload was applied to the femoral head, followed by loading to failure at a rate of 10 mm/s until fracture, indicated by 30 % drop in axial force. RESULTS: THE THREE ENTRY POINTS DID NOT DIFFER IN LOAD-TO-FAILURE: GT (6378.7 ± 1494.9 N), P (6912.4 ± 4924.1 N) and CC (7044.2 ± 2911.4 N) (P = 0.948) or maximum displacement, stiffness, and toughness. Most PF specimens failed at the basicervical neck, whereas most GT specimens failed at the subcapital neck; these differences were not significant. CC specimens failed evenly split between subcapital and basicervical. CONCLUSION: There were no significant difference in femoral neck load-to-failure after placement of a reconstruction nail through a CC entry portal when compared to both GT and PF entry. Clinically, this suggests the CC entry portal is a viable option when clinical considerations warrant its use.

Cattle hair as a bioindicator for short- and medium-chain chlorinated paraffin monitoring on cattle farms.

Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are hazardous industrial chemicals that tend to bioaccumulate in animal-derived foodstuffs through the food supply chain. However, the lack of reliable noninvasive bioindicators hinders the monitoring of farm animal exposure to CPs. In this study, 169 cattle hair samples were collected from beef cattle farms in six Chinese provinces, with further beef, feed, and soil samples being collected in Hebei province. Geographical differences in CP concentrations were observed in the hair samples, and CP concentrations in samples collected from Hebei province decreased in the following order: hair > feed > beef > soil. C10-11Cl6-7 and C14Cl7-8 were the predominant SCCPs and MCCPs, respectively, in all the hair, beef, feed, and soil samples. CP concentrations in hair samples significantly correlated with those in beef, feed, and soil samples, indicating that hair can be used as a bioindicator of cattle exposure to CPs. The possible health risks associated with exposure to CPs through beef consumption, especially for children and high-volume beef consumers, should be further investigated.

Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.

High-grade neuroendocrine head and neck cancer: Case series and review of the literature.

BACKGROUND: High-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years. METHODS: A retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre. RESULTS: During the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44-86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1-96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %. CONCLUSION: This case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.

Transcriptomic and epigenetic landscape of nimorazole-enhanced radiochemotherapy in head and neck cancer.

BACKGROUND: Hypoxia remains a challenge for the therapeutic management of head and neck squamous cell carcinoma (HNSCC). The combination of radiotherapy with nimorazole has shown treatment benefit in HNSCC, but the precise underlying molecular mechanisms remain unclear. PURPOSE: To assess and to characterize the transcriptomic/epigenetic landscape of HNSCC tumor models showing differential therapeutic response to fractionated radiochemotherapy (RCTx) combined with nimorazole. MATERIALS/METHODS: Bulk RNA-sequencing and DNA methylation experiments were conducted using untreated and treated HNSCC xenografts after 10 fractions of RCTx with and without nimorazole. These tumor models (FaDu, SAS, Cal33, SAT and UT-SCC-45) previously showed a heterogeneous response to RCTx with nimorazole. The prognostic impact of candidate genes was assessed using clinical and gene expression data from HNSCC patients treated with primary RCTx within the DKTK-ROG. RESULTS: Nimorazole responder and non-responder tumor models showed no differences in hypoxia gene signatures However, non-responder models showed upregulation of metabolic pathways. From that, a subset of 15 differentially expressed genes stratified HNSCC patients into low and high-risk groups with distinct outcome. CONCLUSION: In the present study, we found that nimorazole non-responder models were characterized by upregulation of genes involved in Retinol metabolism and xenobiotic metabolic process pathways, which might contribute to identify mechanisms of resistance to nitroimidazole compounds and potentially expand the repertoire of therapeutic options to treat HNSCC.

Tips for Transient Perivascular Inflammation of the Carotid Artery Syndrome.

BACKGROUND: Idiopathic carotidynia, also known as transient perivascular inflammation of the carotid artery (TIPIC) syndrome, is a rare, self-limited, clinical-radiologic entity. Over the years, the diagnosis of carotidynia has been controversial, but recent pathologic, radiologic, clinical, and laboratory findings support an inflammatory etiology. CASE REPORT: A 61-year-old woman with a history of hypertension, left lower extremity liposarcoma, and right internal jugular port placement 2 weeks prior with initiation of chemotherapy presented to the emergency department with right neck pain and swelling of the lateral neck and lower face for the past 3 days. Computed tomography-neck with IV contrast revealed marked mural thickening of the right common carotid artery, which can be seen with carotidynia (Fay syndrome and TIPIC syndrome) and vasculitis. The patient had elevated inflammatory markers and was treated clinically for carotidynia with ibuprofen, evaluated by vascular surgery, and discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The causes of acute neck pain are diverse, ranging from nonemergent to surgically emergent etiologies. As radiologists and emergency physicians, we believe TIPIC syndrome is a rare entity with important clinical impact deserving attention, as it is not typically included in medical training and is usually learned only through years of clinical experience and practice. TIPIC syndrome requires a unique combination of both clinical and radiologic findings to diagnose accurately and appropriately. It is important to be familiar with this diagnosis because treatment is focused on symptomatic relief without the need for invasive procedures. Our goal was to increase awareness of this uncommon diagnosis to improve patient care by preventing unnecessary invasive procedures and aid in timely and accurate diagnosis.

Nodal Metastases in Stage 3 Head and Neck Melanoma: Patterns of Metastases and Patterns of Failure.

OBJECTIVE: Stage 3 patients with clinically positive nodal metastasis are treated with therapeutic neck dissection and adjuvant systemic therapy. The aim of our study was to examined the predictability of pre-operative CT as a nodal drainage assessment tool. METHODS: Retrospective review of all patients with clinically positive head and neck cutaneous melanoma between 2010 and 2019. Clinical disease was diagnosed as radiological suspicious, biopsy-proven node. A pre-operative CT evaluation for nodal metastasis was compared to pathology report. RESULTS: A total of 53 patients were included. Forty patients (75.5%) were males with a mean age of 59 (SD 15.52). The majority of patients (26.4%) had an unknown primary site. The most common sites for primary were the cheek in eight patients (15.1%) followed by forehead (9.4%) and lateral neck (9.4%). Preoperative CT predicted nodal disease in 84.6% of cases. The primary region that mainly failed from the previously described clinical prediction was the upper anterior neck with 83.3% parotid involvement. A total of 10 patients (18.9%) were diagnosis with non-clinical nodes on pathology with a median non-clinical node of 1 (range 1-2). Of them, 9 (90%) were in the same clinical levels detected by CT. Pre-operative CT was associated with a neck level accuracy of 98.1%. CONCLUSION: Stage 3 head and neck melanoma with clinically positive nodal metastasis that are eligible for an adjuvant systemic treatment, may benefit from a highly selective neck dissection according to their pre-operative imaging studies. This should be further evaluated in a large-scale clinical trial. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Primary phenotypic features associated with caudal neck pathology in warmblood horses.

BACKGROUND: Detailed descriptions of clinical signs associated with radiological findings of the caudal cervical vertebral column are not available. OBJECTIVES/HYPOTHESES: Describe the clinical features associated with neck pain or stiffness, neck-related thoracic limb lameness, proprioceptive ataxia consistent with a cervicothoracic spinal cord or nerve lesion, and their frequency of occurrence compared with control horses. ANIMALS: A total of 223 Warmblood horses. METHODS: Case-control study. Controls and cases were recruited prospectively. All horses underwent predetermined lameness and neurologic examinations. The frequency of occurrence of each clinical feature was compared between cases and controls and relative risk (RR) were calculated. RESULTS: Ninety-six cases and 127 controls were included. Forty-seven (49%) of the cases were classified as neurologic, 31 (32.3%) had thoracic limb lameness, and 18 (18.7%) had neck stiffness or pain or both. Focal caudal cervical muscle atrophy (46, 47.9%), hypoesthesia (38, 39.6%), patchy sweating (16, 16.7%), hyperesthesia (11, 11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (58, 60.4%) were only observed in cases (P < .001). Sideways flexion of the neck was restricted in a higher proportion of cases (47/96, 49%) compared with controls (40/127, 31.8%; P = .009, RR 1.5). Hopping-type thoracic limb lameness was only observed in cases, (30, 31.6%). Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (41.9%) cases. CONCLUSIONS AND CLINICAL IMPORTANCE: Systematic clinical evaluation using the methods described should enable clinical differentiation between horses with caudal cervical lesions and horses with other causes of gait abnormalities.

Negative Pressure Wound Therapy with Instillation and Dwell Time for Pharyngocutaneous Fistula.

Pharyngocutaneous fistula is a critical complication of head and neck cancer reconstruction and it is often difficult to manage. We herein report two cases of pharyngocutaneous fistulas that developed after oropharyngeal reconstruction and were successfully treated with negative pressure wound therapy with instillation and dwell time (NPWTi-d), an advanced form of traditional NPWT. NPWTi-d may be a useful nonsurgical treatment for pharyngocutaneous fistula. Laryngoscope, 2024.

Impact of subclinical neck pain on eye and hand movements in goal-directed upper limb aiming movements.

Individuals with untreated, mild-to-moderate recurrent neck pain or stiffness (subclinical neck pain (SCNP)) have been shown to have impairments in upper limb proprioception, and altered cerebellar processing. It is probable that aiming trajectories will be impacted since individuals with SCNP cannot rely on accurate proprioceptive feedback or feedforward processing (body schema) for movement planning and execution, due to altered afferent input from the neck. SCNP participants may thus rely more on visual feedback, to accommodate for impaired cerebellar processing. This quasi-experimental study sought to determine whether upper limb kinematics and oculomotor processes were impacted in those with SCNP. 25 SCNP and 25 control participants who were right-hand dominant performed bidirectional aiming movements using two different weighted styli (light or heavy) while wearing an eye-tracking device. Those with SCNP had a greater time to and time after peak velocity, which corresponded with a longer upper limb movement and reaction time, seen as greater constant error, less undershoot in the upwards direction and greater undershoot in the downwards direction compared to controls. SCNP participants also showed a trend towards a quicker ocular reaction and movement time compared to controls, while the movement distance was fairly similar between groups. This study indicates that SCNP alters aiming performances, with greater reliance on visual feedback, likely due to altered proprioceptive input leading to altered cerebellar processing.

Proton therapy re-irradiation outcomes and genomic landscape of patients with recurrent head and neck cancer.

INTRODUCTION: Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is challenging. We describe clinical outcomes and toxicity of proton therapy (PT) for recurrent HNC, and report genomic alterations associated with patterns of failure. MATERIALS & METHODS: We performed a retrospective analysis of rHNC patients treated with PT. Outcomes were estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA) were performed to assess multiple patient factors. Next-generation sequencing and genomic analyses were performed on available samples. RESULTS: Eighty-nine patients treated with PBS-PT for rHNC with a median follow-up of 12 mo (0-71 mo) were included. The 1- and 2-y local control (LC) rates were 80.8 % (95 % CI: 70.8-90.8) and 66.2 % (95 % CI: 50.7-81.7), and 1- and 2-y distant metastasis-free survival (DMFS) were 41.0 % (95 % CI: 30.0-52.0) and 26.3 % (95 % CI: 15.7-36.9). The median overall survival (OS) was 13 mo (95 % CI: 9.3-16.7). On UVA and MVA, smaller gross tumor volume (GTV) was associated with improved OS (HR 1.002, P = 0.004), DMFS (HR 1.002, P = 0.004), and PFS (HR 1.002, P = 0.014). There were 35 late Gr3 + toxicity events (30.3 %). Patients with higher candidate gene-specific mutation burden (genes with [OR] > 2, P < 0.05) had inferior PFS. TP53, NOTCH4, and ARID1B mutations were associated with inferior DMFS (OR > 2, P < 0.05). CONCLUSIONS: PBS-PT is effective at achieving LC for rHNC with favorable toxicity. Distant metastases are common, and associated with TP53, NOTCH4, and ARID1B mutations. Inclusion of genomic alterations in the clinical decision process may be warranted.

Lymph node metastasis burden identifies head and neck squamous cell carcinoma patients benefiting from adjuvant chemoradiation: A propensity score-matching.

INTRODUCTION: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. RESULTS: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. CONCLUSION: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V.

The partial adaptation strategy for online-adaptive proton therapy: A proof of concept study in head and neck cancer patients.

BACKGROUND: The accuracy of intensity-modulated proton therapy (IMPT) is greatly affected by anatomy variations that might occur during the treatment course. Online plan adaptations have been proposed as a solution to intervene promptly during a treatment session once the anatomy changes are detected. The implementation of online-adaptive proton therapy (OAPT) is still hindered by time-consuming tasks in the workflow. PURPOSE: The study introduces the novel concept of partial adaptation and aims at investigating its feasibility as a potential solution to parallelize tasks during an OAPT workflow for saving valuable in-room time. METHODS: The proof-of-principle simulation study includes datasets from six head and neck cancer (HNC) patients, each consisting of one planning CT (pCT) and three contoured control CTs (cCTs). Robust 3-field normo-fractionated initial IMPT plans were generated on the pCTs with a standardized field configuration, delivering 66 Gy and 54 Gy to the high-risk and low-risk clinical target volume (CTVHigh and CTVLow), respectively. For each cCT, a dose-mimicking-based partial adaptation was applied: two fields were adapted on the current anatomy taking into account the background dose of the first non-adapted field supposedly delivered in the meantime. Fraction doses on the cCTs resulting from partially adapted plans with different first (non-adapted) field assignments were compared against those from non-adapted and fully adapted plans regarding target coverage and organs at risk (OARs) sparing. The robustness of partially adapted plans was also evaluated. RESULTS: Partially adapted plans showed comparable results to fully adapted plans and were superior to non-adapted plans for both target coverage and OAR sparing. Target coverage degradation in the non-adapted plans (median D98%: 95.9% and 97.5% for CTVLow and CTVHigh, respectively) was recovered by both partial (98.0% and 98.5%) and full adaptation (98.2% and 98.7%) in comparison to the initial plans (98.7% and 98.8%). The initial hotspot dose for the CTVHigh (median D2%: 101.8%) increased in the non-adapted plans (102.9%) and was recovered by the adaptive strategies (partial: 102.5%, full: 101.9%). The near-maximum dose (D0.01cc) to brainstem and spinal cord was within clinical constraints for all investigated dose distributions, but clearly increased for no adaptation and improved in the (both partially and fully) adapted plans with respect to the non-adapted ones. The parotids' median doses (D50) were mainly patient-specific depending on the proximity to the target region, but anyway lower for the partially and fully adapted plans compared to the non-adapted ones. OAR sparing was furthermore improved for the partially adapted plans in comparison to full adaptation. Robustness of the target dose metrics was preserved in all evaluated scenarios. CONCLUSIONS: For OAPT of HNC patients, partial adaptation is able to generate plans of superior conformity to non-adapted plans and of comparable conformity as fully adapted plans, while having the potential to speed up the online-adaptive workflows. Thus, partial adaptation represents an intermediate approach until fast online adaptation workflows become available. Furthermore, it can be applied in workflows where online treatment verification stops the delivery and triggers an online adaptation for the remaining fraction.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

Generative AI and Otolaryngology-Head & Neck Surgery.

The increasing development of artificial intelligence (AI) generative models in otolaryngology-head and neck surgery will progressively change our practice. Practitioners and patients have access to AI resources, improving information, knowledge, and practice of patient care. This article summarizes the currently investigated applications of AI generative models, particularly Chatbot Generative Pre-trained Transformer, in otolaryngology-head and neck surgery.

What are the costs of managing neck and low back pain in Brazil? Investigation of a ten-year period from the perspective of the Brazilian public health system.

INTRODUCTION: Considering the prospects of increased prevalence and disability due to neck and low back pain, it is relevant to investigate the care processes adopted, to assist future public policies and decision-making for a better allocation of resources. Objective: the aim of this study was to estimate the costs arising from inpatient and outpatient care of individuals with Neck Pain (NP) and Low Back Pain (LBP) in Brazil, between 2010 and 2019. METHODS: This is a cost-of-illness study from the perspective of the Brazilian public health system, based on health conditions with high prevalence (neck and low back pain). Data were presented descriptively using absolute and relative values. RESULTS: Between 2010 and 2019, the health system spent more than $600 million (R$ 2.3 billion) to treat NP and LBP in adults, and LBP accounted for most of the expenses. Female had higher absolute expenses in inpatient care and in the outpatient system. CONCLUSION: Our study showed that the costs with NP and LBP in Brazil were considerable. Female patients had higher outpatient costs and male patients had higher hospitalization costs. Healthcare expenses were concentrated for individuals between 34 and 63 years of age.

This study focused on understanding how much it cost to treat neck pain (NP) and low back pain (LBP) in Brazil between 2010 and 2019, from the point of view of the public health system (i.e. Unified Health System ­ SUS). The idea was to find out how much money was spent and where. It turned out that the SUS spent, in total, more than US$600 million (R$2.3 billion) with LBP responsible for most of these expenses. Furthermore, we noted that women had higher outpatient care costs, while men had higher hospitalization costs. Those costs were more concentrated in people aged between 34 and 63 years.

Tumor-stroma contact ratio - a novel predictive factor for tumor response to chemoradiotherapy in locally advanced oropharyngeal cancer.

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package "Spatstat". TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance. Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61). In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.