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Urothelial carcinoma of the bladder comprises a spectrum of illnesses ranging from nonmuscle-invasive to muscle-invasive to advanced/metastatic disease. Each of these clinical states is characterized by a unique pathogenesis, prognosis and approach to treatment. However, given the heterogeneity of urothelial carcinoma, differences in biology and outcomes exist not only among these clinical states but also within each state. Personalized medicine, also commonly referred to as individualized or stratified medicine, offers the potential to optimize treatment for a given patient, based on the ability to accurately predict prognosis, response to treatment and tolerability of treatment. This review will discuss recent efforts, current challenges and future opportunities, for the personalized management of urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Background: Risk prediction models for hepatocellular carcinoma are available for individuals with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections who are at high risk but not for the general population with average or unknown risk. We developed five simple risk prediction models based on clinically available data from the general population.Methods: A prospective cohort of 428 584 subjects from a private health screening firm in Taiwan was divided into two subgroups-one with known HCV test results (n = 130 533 subjects) and the other without (n = 298 051 subjects). A total of 1668 incident hepatocellular carcinomas occurred during an average follow-up of 8.5 years. Model inputs included age, sex, health history-related variables; HBV or HCV infection-related variables; serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alfa-fetoprotein (AFP), as well as other variables of routine blood panels for liver function. Cox proportional hazards regression method was used to identify risk predictors of hepatocellular carcinoma. Receiver operating characteristic curves were used to assess discriminatory accuracy of the models. Models were internally validated. All statistical tests were two-sided.Results: Age, sex, health history, HBV and HCV status, and serum ALT, AST, AFP levels were statistically significant independent predictors of hepatocellular carcinoma risk (all P < .05). Use of serum transaminases only in a model showed a higher discrimination compared with HBV or HCV only (for transaminases, area under the curve [AUC] = 0.912, 95% confidence interval [CI] = 0.909 to 0.915; for HBV, AUC = 0.840, 95% CI = 0.833 to 0.848; and for HCV, AUC = 0.841, 95% CI = 0.834 to 0.847). Adding HBV and HCV data to the transaminase-only model improved the discrimination (AUC = 0.933, 95% CI = 0.929 to 0.949). Internal validation showed high discriminatory accuracy and calibration of these models.Conclusion: Models with transaminase data were best able to predict hepatocellular carcinoma risk even among subjects with unknown or HBV- or HCV-negative infection status. [ABSTRACT FROM AUTHOR]

There have been more drugs approved by the US Food and Drug Administration for the treatment of castration-resistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from "bench to bedside," the recent successes in the treatment of prostate cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castration-resistant disease are evaluated. This review will explore the shifting paradigm in drug development for castration-resistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease. [ABSTRACT FROM AUTHOR]

Pathological lymph node metastases (pN+) are an established prognostic factor in oral cavity squamous cell carcinoma (OSCC). We retrospectively examined the prognostic significance of lymph node (LN) density in pN+ OSCC patients who underwent neck dissection (ND) and postoperative adjuvant therapy. We examined 309 pN+ patients who underwent levels I-III ND and 148 pN+ patients treated with levels I-V ND. The 5-year control and survival rates served as the main outcome measures. The 5-year rates for patients treated with levels I-III and I-V NDs were as follows: local control, 79%, 74% (p=0.0630); neck control, 81%, 68% (p=0.0014); distant metastasis, 21%, 36% (p=0.0003); disease-free survival (DFS), 59%, 43% (p=0.0001); disease-specific survival (DSS), 66%, 46% (p<0.0001); and overall survival (OS), 49%, 37% (p=0.0048), respectively. Multivariate analysis demonstrated that an LN density 0.16 was an independent prognostic factor for 5-year neck control (all data presented as p, hazard ratio [95% confidence interval]) (0.003, 2.691 [1.412-5.128]), distant metastases (0.001, 2.831 [1.520-5.270]), DFS (<0.001, 2.464 [1.571-3.866]), and DSS (0.036, 1.781 [1.040-3.052]) in levels I-III ND patients. An LN density 0.048 was an independent predictor of 5-year local control (0.004, 4.871 [1.654-14.344]), neck control (0.002, 24.738 [3.367-181.771]), DFS (<0.001, 4.151 [2.264-7.610]), DSS (<0.001, 3.791 [2.017-7.125]), and OS (<0.001, 2.806 [1.706-4.613]) in levels I-V ND patients. Our findings demonstrate the prognostic value of LN density for guiding treatment strategies in OSCC patients who are to receive adjuvant therapy. [ABSTRACT FROM AUTHOR]

The prognosis of well-differentiated oral cavity squamous cell carcinoma (OSCC) is better than less-well-differentiated neoplasms. The aim of this retrospective study was to identify prognostic factors in patients with well-differentiated OSCC. The 5-year outcomes of 467 patients with well-differentiated OSCC who underwent radical surgery and neck dissection were analyzed. In the entire cohort, the presence of pathological node metastases (pN+ vs. pN0) was an independent predictor of 5-year outcomes. In pN0 patients, tumor depth (8mm) was the only independently prognostic factor for 5-year survival rates on multivariable analysis (disease-free survival [DFS], P=0.001, hazard ratio [HR]=2.634, 95% confidence interval [95% CI]=1.496-4.636; disease-specific survival [DSS], P<0.001, HR=6.794, 95% CI=2.364-19.525). In pN+ patients, level IV/V neck nodal metastases (DFS, P<0.001, HR=47.483, 95% CI=8.942-252.122; DSS, P<0.001, HR=14.301, 95% CI=5.337-38.323), and 3 positive nodes (DFS, P=0.037, HR=2.107, 95% CI=1.047-4.242; DSS, P=0.044, HR=2.093, 95% CI=1.020-4.295) were independently associated with 5-year outcomes. Our results suggest that a tailored treatment approach in well-differentiated OSCC patients should take into account the presence of either pN0 or pN+ disease. [ABSTRACT FROM AUTHOR]

Objectives: Androgen receptor targeted therapies (ARTs) are widely preferred over taxane chemotherapy due to their good tolerability and similar efficacy. However, there is a paucity of data that support the use of ART therapy or describe end-of-life (EOL) outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) with reduced performance status (PS) (European Cooperative Oncology Group [ECOG] ≥2)., Methods: We performed a retrospective, single-institution study of 142 patients with mCRPC who received ART therapy between 2010 and 2021. We assessed each record for baseline demographic and clinical information, ART treatment course, and survival and EOL outcomes. Our primary aim was to compare overall survival (OS) between the two groups (ECOG ≥2 vs 0 to 1), and our secondary aim was to describe EOL outcomes. Fisher exact tests and Wilcoxon signed-rank tests were used to compare baseline characteristics. Cox regression was used to compare OS for patients with ECOG ≥2 at the start of treatment with those who had an ECOG of 0 or 1. Descriptive analyses were performed to assess EOL outcomes between the groups., Results: Patients with mCRPC and decreased PS experienced shorter OS on ART compared with those with higher PS. Moreover, when examining EOL outcomes, a near majority of these patients died in the hospital, with a greater percentage among those with an ECOG ≥2., Conclusion: These findings highlight the need for continual assessment of PS, improved shared decision-making in ART treatment, and additional research exploring the association between PS and EOL outcomes., Competing Interests: V.G.P. is a full-time employee at Arvinas. He has received consulting fees from Seagen and Astellas. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery., Methods: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV., Results: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05)., Conclusions: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC., Methods: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis., Results: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001)., Conclusions: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity., Methods: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC., Results: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P =0.016), rash (OR: 13.4, CI: [1.35-134.81]; P =0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P =0.019)., Conclusions: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden., Competing Interests: V.G.P. is a full-time employee of Arvinas. He has received consulting fees from Seagen and Sanofi Genzyme. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities., Patients and Methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted., Results: A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively., Conclusion: The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors., Competing Interests: Disclosure None of the authors disclose any potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Oral submucous fibrosis is a global health concern associated with betel quid use and results in trismus, which can be either primary or secondary in origin. Severe cases often require trismus release with free-flap reconstruction. This study examined longitudinal outcome trends following trismus release and compared the outcomes of patients with primary and secondary oral submucous fibrosis-related trismus., Methods: We conducted a retrospective cohort study by including patients who underwent trismus release between 2013 and 2022. All procedures were performed by a single surgical team to ensure technique standardisation. We measured the maximum mouth opening, the interincisal distance, perioperatively and 1, 2, 3, 4, 6 and 12 months post-operatively. Data were analysed using generalised estimating equations., Results: A total of 35 patients were included in the study, 17 with primary and 18 with secondary oral submucous fibrosis-related trismus. Initially, patients with primary oral submucous fibrosis-related trismus had greater interincisal distance gains than those with secondary oral submucous fibrosis-related trismus (p = 0.015 and p = 0.025 at 3 and 4 months post-operatively, respectively). However, after 12 months, this initial advantage faded, with comparable interincisal distance improvements in patients with primary and secondary disease, despite the more complex surgical procedures required in secondary cases., Conclusion: Surgeons should carefully consider the benefits of trismus release procedures for patients with secondary oral submucous fibrosis-related trismus by recognising the changes in post-operative outcomes., Competing Interests: Conflict of Interest Statement None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC)., Methods: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145)., Results: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001., Conclusions: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm., Methods: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted., Results: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398)., Conclusions: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: This study evaluates serial radiographic changes in the maxillary sinus of patients with oral cancer after an inferior maxillectomy and a soft tissue free flap reconstruction., Methods: Fifty-six patients were evaluated between Oct 2005 and Mar 2017 from an institutional database. Preoperative and surveillance imaging was reviewed at set time-points. Maxillary sinus scores were allotted based on a modification of the Lund-MacKay staging system. Patients were evaluated for change in sinus score. A univariate (UV) and multivariate (MV) analysis was performed., Results: There were 53.5% T3/T4 category tumors and 68% received adjuvant treatment. Median follow-up was 24.4 months. Preoperative mean sinus score was 0.27 ± 0.44 and postoperative mean sinus score at 24 months was 1.2 ± 1.3 (p = <0.001). On UV analysis advanced T-stage at 12 months (OR 6.7, 95% CI 1.2-50.3, p = 0.01) and 24 months (OR 5.2, 95% CI 1.03-36.8, p = 0.04) was associated with significantly higher sinus score. On MV analysis, advanced T-stage continued to be associated with increased odds for higher sinus score (OR 4.9, 95% CI 1.1-26.8, p = 0.039)., Conclusion: A mild increase in postoperative sinus score is seen in this cohort of patients. Advanced T-stage is associated with increased odds for higher sinus scores., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Reconstruction of the oral cavity commonly results in trismus and lip incompetence., Aim and Objectives: In this study, we aim to describe an innovative design of a radial forearm free flap for resurfacing bilateral buccal defects and simultaneous functional lower lip reconstruction in a single stage., Materials and Methods: Between January 2010 and December 2019, 6 males underwent simultaneous buccal and lower lip reconstruction with a radial forearm free flap. The mean age of the patients was 57.3 years (range, 50-68 years). The defects were caused by trismus release and due to previous treatments. The mean size of the defects was 17.9 cm in length and 3.25 cm in width. Flaps were harvested, including the proximal perforators of the radial vessels, and the inset began in the buccal area opposite the anastomosis side., Results: Flap size ranged from 16 to 21 × 2 to 4 cm. The recipient vessels used were the superficial temporal (4) and facial (2). All flaps survived. Lip infection was seen in 2 cases and managed conservatively. The mean follow-up was 19.2 months (range, 12-28 months). The mean increase in the interincisal distance was 10.7 mm. Oral continence was good in all patients. Speech intelligibility was considered total in 4 patients and partial in the remaining 2., Conclusion: The radial forearm flap constitutes an option for simultaneous lower lip reconstruction and resurfacing of bilateral buccal areas after trismus release. The procedure provides a thin and pliable reconstruction using only 1 donor site and 1 set of recipient vessels., Competing Interests: Conflicts of interest and sources of funding: All authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria., Methods: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO)., Results: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%)., Conclusions: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.

Extensive resections of advanced stage oral cavity cancers can sometimes lead to significant through and through buccal defects with compromise of the oral commissure/lips. Post free flap reconstruction, such patients often require a secondary delayed commissuroplasty to assist with improved oral function and quality of life. In current literature, limited methods exist for free flap commissuroplasty with some key limitations, particularly their negative impact on buccal sulcus or oral vestibule. Our technique of the triangular cheek flap commissuroplasty allows the surgeon to reconstruct a neo-commissure without compromising the oral vestibular depth or decreasing mouth opening. Through this pictorial essay we describe a detailed surgical technique for secondary reconstruction of the oral commissure., (© 2023 Wiley Periodicals LLC.)

Purpose: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors., Methods: We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05., Results: Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; P = 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P = 0.0031)., Conclusions: Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Free flap monitoring is essential for postmicrosurgical management and outcomes but traditionally relies on human observers; the process is subjective and qualitative and imposes a heavy burden on staffing. To scientifically monitor and quantify the condition of free flaps in a clinical scenario, we developed and validated a successful clinical transitional deep learning (DL) model integrated application., Material and Methods: Patients from a single microsurgical intensive care unit between 1 April 2021 and 31 March 2022, were retrospectively analyzed for DL model development, validation, clinical transition, and quantification of free flap monitoring. An iOS application that predicted the probability of flap congestion based on computer vision was developed. The application calculated probability distribution that indicates the flap congestion risks. Accuracy, discrimination, and calibration tests were assessed for model performance evaluations., Results: From a total of 1761 photographs of 642 patients, 122 patients were included during the clinical application period. Development (photographs =328), external validation (photographs =512), and clinical application (photographs =921) cohorts were assigned to corresponding time periods. The performance measurements of the DL model indicate a 92.2% training and a 92.3% validation accuracy. The discrimination (area under the receiver operating characteristic curve) was 0.99 (95% CI: 0.98-1.0) during internal validation and 0.98 (95% CI: 0.97-0.99) under external validation. Among clinical application periods, the application demonstrates 95.3% accuracy, 95.2% sensitivity, and 95.3% specificity. The probabilities of flap congestion were significantly higher in the congested group than in the normal group (78.3 (17.1)% versus 13.2 (18.1)%; 0.8%; 95% CI, P <0.001)., Conclusion: The DL integrated smartphone application can accurately reflect and quantify flap condition; it is a convenient, accurate, and economical device that can improve patient safety and management and assist in monitoring flap physiology., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition., Methods: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation., Results: The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively., Conclusion: Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Trismus after oral cancer is frequent, with scarce evidence of surgical release treatment in these patients., Objectives: The objective of this study is to determine the results of trismus release and free flap reconstruction after oral cancer treatment, establish immediate and long-term results, and detect factors that influence outcome., Materials and Methods: A retrospective study was performed. Preoperative, intraoperative, and follow-up interincisal distances were measured. The intraoperative, long-term gain, and postoperative loss were calculated. Analysis of the long-term results with the preoperative and intraoperative variables was performed., Results: Surgical release immediately increased the interincisal distance by 29.25 mm. Sixty-six percent of this gain was lost due to trismus recurrence, giving a long-term interincisal gain of 9.90 mm. Worse results were observed in patients with previous high-stage tumors, maxillectomies, skin resections, and previous radiotherapy. The were no significant differences in the results depending on the type of release or reconstruction performed, with the exception of the reconstruction with the sural flap, which presented worse results. Patients with trismus of ≤10 mm could have more range for improvement after this surgery., Conclusions: The results of this surgery are moderate in the long term due to high trismus recurrence in spite of aggressive treatment., (© 2023 Wiley Periodicals LLC.)

Background: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC., Methods: Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment., Results: Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin., Conclusion: In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Marginal mandibulectomy with or without additional mandibulotomy could represent the alternatives to avoid segmental mandibulectomy in carefully selected tongue cancers., Aim and Objectives: This study investigated a subgroup of tongue cancers with suspected involvement to the alveolar bone because of the shallow and deformed mouth floor. We aimed to compare the functional outcomes, postoperative complications, and disease control efficacy between the 2 different marginal mandibulectomy approaches, with or without additional mandibulotomy., Materials and Methods: A retrospective study of 29 marginal mandibulectomies and 26 combined mandibulotomies for tongue cancer wide excisions and flap reconstruction at Chang Gung Memorial Hospital Linkou Branch during 2014 to 2019 was performed., Results: The combined mandibulotomy group had more advanced T-status ( P < 0.001) and greater tumor diameters ( P < 0.001) but not increased preexisting trismus, bone invasions, or positive margins. The additional mandibulotomy increased flap necrosis ( P = 0.044), late infections ( P = 0.004), and tongue movement limitations ( P = 0.044) but not osteoradionecrosis. Osteoradionecrosis was unrelated to the resected mandibular length or the mandibulotomy sites. Feeding tube dependence was greater in the combined group at discharge ( P = 0.014), but no long-term differences were noted. Kaplan-Meier overall survival ( P = 0.052) and disease-free survival ( P = 0.670) were both comparable between the 2 groups., Conclusions: The combined procedure of mandibulotomy and marginal mandibulectomy in large tongue cancers without bone invasions is associated with increased soft tissue-related complications but not bone-related complications. However, comparable disease control, survival, and long-term tube feeding outcomes were noted., Competing Interests: Conflicts of interest: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Large defects of the lower lip pose a difficult challenge for any reconstructive surgeon. When there is limited local tissue available to resurface the defects, free flaps are the preferred option., Aim and Objectives: We reported our experience in the reconstruction of extensive lower lip defects. The authors propose a new algorithm for microsurgical technique selection and assessment of the functional outcomes obtained., Materials and Methods: A retrospective review of all microsurgical reconstructions of extensive lower lip defects by the senior author for 10 years was performed. The functional outcomes assessed included speech, feeding, and oral continence. Patients were stratified according to their status of simultaneous mandible resection (none, marginal, segmental)., Results: Fifty-one patients were included in this study. Almost all patients (96.1%) achieved intelligible speech. Only 1 patient experienced severe drooling. Most patients could eat a solid or soft diet (72.5%). Mandible resection was associated with the worst feeding outcomes., Conclusions: Microsurgical reconstruction of extensive lip defects is safe and provides good results. Free flap selection should take into account the location of the defect, the resected structures, and the body mass index of the patient. Feeding status seems to be inversely correlated with the amount of mandibular resection., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC., Methods: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse., Results: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81])., Conclusion: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification., (© 2023. The Author(s).)

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance  =  0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively ( P   =  .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan., Materials and Methods: A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching., Results: The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p <0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p =0.0002; HR for 5-year overall survival [OS] = 1.17, p =0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p <0.0001; HR for 5-year OS = 1.48, p <0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p =0.0002; OS, 71%/68%, p =0.0269; after PS matching: DSS, 84%/72%, p <0.0001; OS, 75%/66%, p <0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7% / 57.0%, p <0.0001)., Conclusions: Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Lee, Lee, Ng, Liu, Chien, Lin, Wang, Terng, Hua, Chen, Chen, Tsai, Kang, Tsai, Chu, Lin, Fan, Wang, Hsieh, Yeh, Lin, Tsao, Yen, Cheng, Fang, Huang, Lee, Fang, Wang, Lin, Hsin and Wen.)

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ± 0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background:  Superficial temporal vessels have been used successfully as recipient vessels for head and neck reconstruction. This study evaluates the impact of several treatment variables on flap failure and take-back rate when using these recipient vessels., Methods:  We conducted a retrospective study of all microsurgical reconstructions using superficial temporal vessels as recipient vessels in a period of 10 years. Variables collected included previous treatments (radiotherapy, chemotherapy, neck dissection, free flap reconstruction), type of flaps used (soft tissue, osteocutaneous), and vessel size discrepancy between donor and recipient vessels., Results:  A total of 132 patients were included in the study. The flap success rate was 98.5%. The take-back rate was 10.6%. The most frequent reason for take-back was venous congestion secondary to thrombosis. None of the studied variables was associated with flap failure. Reconstructions using osteocutaneous flaps and vein diameter discrepancy (ratio ≥ 2:1) had significantly higher take-back rates., Conclusion:  Flaps with a significant size discrepancy between donor and recipient veins (ratio ≥ 2:1) and fibula flaps (compared with soft tissue flaps) were associated with a higher risk of take-back. It is crucial to minimize venous engorgement during flap harvest and anastomosis, and limit vein redundancy during flap in-setting., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Patients affected by oral tongue squamous cell carcinoma (OTSCC) underwent a supraomohyoid neck dissection (SOHND) or modified radical neck dissection (mRND) according to the clinical nodal status (cN0 vs. cN+). We investigate whether the type of neck dissection affects survival with the presence of extranodal extension (ENE) and multiple nodal metastases (MNM)., Methods: We conducted a retrospective study enrolling surgically treated patients affected by cT1/T2 OTSCC and MNM or ENE. The outcomes assessed were: overall survival (OS), disease-free survival (DFS), and neck-control- and metastases-free survival (NC-MFS). Survival curves were plotted by the Kaplan-Meier method and the log-rank test. Furthermore, we conducted a multivariable analysis with the Cox regression model., Results: We included a total of 565 patients (36% cT1, 64% cT2). Of these, 501 patients underwent a SOHND, and 64 underwent an mRND. A total of 184 patients presented rpN+, with 28.7% of these in the SOHND group and 62.5% of these in the mRND group. We identified no significant differences in OS, DFS, and NC-MFS in the whole pN+ cohort, in the MNM, and the ENE subgroups. In the multivariable analysis, the type of ND did not affect OS and DFS., Conclusions: Treating cT1-2 N0/+ tongue cancer with SOHND is oncologically safe. ENE and MNM patients do not benefit from an mRND.

Objective: To test whether body mass index (BMI) amongst patients with metastatic castration-resistant prostate cancer (mCRPC) is associated with overall survival (OS) and cancer-specific survival., Methods: Individual patient data from 1577 men with mCRPC treated with docetaxel and prednisone from the control arms of ASCENT2, VENICE, and MAINSAIL were considered. The role of BMI on survival outcomes was investigated both as a continuous and categorical variable (≤24.9 vs. 25-29.9 vs. ≥30 km/m 2 ). BMI ≥ 30 kg/m 2 was considered obese. Analyses were adjusted for age, PSA, ECOG performance status, number of metastases and prior treatment. The Cox semi-proportional hazard model was used to predict OS, whereas competing risks regression was used for predicting cancer-specific mortality (CSM). To exclude any possible effect attributable to higher doses of chemotherapy (titrated according to body-surface area), we checked for eventual interactions between BMI and chemotherapy dose (both as continuous-continuous and categorical-continuous interactions)., Results: The median (IQR) age for the patient population was 69 (63,74) years with a median (IQR) BMI of 28 (25-31) kg/m 2 . Median follow-up for survivors was 12 months. Of the 1577 patients included, 655 were deceased by the end of the studies. Regarding OS, BMI emerged as a protective factor both as a continuous variable (HR: 0.96; 95% CI: 0.94, 0.99; p = 0.015) and as a categorical variable (obesity: HR: 0.71, 95% CI: 0.53, 0.96; p = 0.027, relatively to normal weight). The protective effect of high BMI on CSM was confirmed both as a continuous (SHR: 0.94; 95% CI: 0.91, 0.98; p = 0.002) and as a categorical variable (obesity SHR: 0.65; 95% CI: 0.45, 0.93; p = 0.018). No interaction was detected between the BMI categories and the docetaxel dose at any level in our analyses (all p » 0.05)., Conclusions: Obese patients with mCRPC had better cancer-specific and overall survival as compared to overweight and normal weight patients. The protective effect of BMI was not related to receiving higher chemotherapy doses. Further studies aimed at elucidating the biological mechanism behind this effect are warranted., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients., Methods: We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes., Results: We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR)., Conclusions: Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy., (© 2022. The Author(s).)

Tracheal reconstruction remains challenged in clinical. We aimed to fabricate scaffolded cartilage sheets with rigid and elastic supports for tracheal reconstruction. The chondrocyte cell infiltration activity was examined in poly-caprolactone sheet scaffolds with various thicknesses and pore sizes after seeding cells on the top surface of the sheet scaffolds. The expression of cartilage-related genes and accumulation of sulfated glycosaminoglycans were elevated in the cell-scaffold composites upon chondrogenic induction. The thicker cartilage sheets represented stronger mechanical properties than the thinner cartilage sheets. Two different cartilage sheets were orthotopically implanted into a trachea in a rabbit model for 2, 4, and 16 weeks. Cartilage-related sulfated glycosaminoglycans and type II collagen macromolecules were stably expressed in the tracheal implants. However, the invasive migration of fibrous tissue and profibrotic collagen fibers into cartilage implants and the peripheral space surrounding the implants were elevated in a time-dependent manner. At week 16 postimplantation, airway stenosis was noticed under the thicker sheet implants, but not the thinner implants, suggesting that the thinner (1 mm thick) scaffolded cartilage sheet was an optimal candidate for tracheal reconstruction in this study. Finally, cartilage sheets could be a reconstructive therapy candidate applied to reconstruct defects in the trachea and other tissues composed of cartilage. Impact statement Tissue engineering is a promising approach to generate biological substitutes. We aimed to develop cartilage sheets as tracheal prosthesis used in tracheal reconstruction or regional repairing in the animal model. The formation of microvessels and the dynamics of reepithelialization were monitored for 16 weeks in tracheal implants of the engineered cartilage sheets. In this study, it was demonstrated that the tissue-engineered cartilage sheets are potential substitutes applied in the reconstruction of the trachea and other tissues composed of cartilage tissue. The cartilage sheets were thought of as biomaterials for personalized regenerative medicine since the dimensions, thickness, and pore sizes of cartilage sheets were tunable to fit the lesions that need to be reconstructed.

The engineering of tracheal substitutes is pivotal in improving tracheal reconstruction. In this study, we aimed to investigate the effects of biomechanical stimulation on tissue engineering tracheal cartilage by mimicking the trachea motion through a novel radial stretching bioreactor, which enables to dynamically change the diameter of the hollow cylindrical implants. Applying our bioreactor, we demonstrated that chondrocytes seeded on the surface of Poly (ε-caprolactone) scaffold respond to mechanical stimulation by improvement of infiltration into implants and upregulation of cartilage-specific genes. Further, the mechanical stimulation enhanced the accumulation of cartilage neo-tissues and cartilage-specific extracellular macromolecules in the muscle flap-remodeled implants and reconstructed trachea. Nevertheless, the invasion of fibrous tissues in the reconstructed trachea was suppressed upon mechanical loading.

Background: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC., Methods: A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes., Results: On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0-3 were 70%/62%/50%/36% ( p < 0.0001) and 61%/52%/40%25%, respectively ( p < 0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% ( p < 0.0001) and 63%/51%/67%/33%, respectively ( p < 0.0001)., Conclusions: Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang, Wen, Lee, Ng, Tsai, Lee, Chu, Lin, Fan, Wang, Hsieh, Yeh, Lin, Tsao, Fang, Huang, Lee, Fang, Wang, Lin, Hsin, Yen, Cheng and Liao.)