HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Regional lymph node changes on breast MRI in patients with early-stage breast cancer receiving neoadjuvant chemo-immunotherapy.

PURPOSE: Establishing breast MRI imaging patterns associated with neoadjuvant immunotherapy is needed to monitor response. We analyzed serial breast MRIs in patients receiving neoadjuvant chemo-immunotherapy on the I-SPY2 clinical trial. METHODS: Patients with stage 2-3 HER2-negative breast cancer were randomized to weekly paclitaxel (control), weekly paclitaxel and pembrolizumab, or weekly paclitaxel, pembrolizumab and intra-tumoral injection of SD-101, a TLR9 agonist. All patients received AC. Regional lymph nodes were retrospectively evaluated on breast MRI at baseline, 3, 12 and 20 weeks by a single blinded radiologist. MRIs were assessed for development of new regional lymphadenopathy, or increase in the longest diameter or cortical thickness of the largest abnormal regional lymph node. RESULTS: Between 12/2015 and 4/2021, a total of 43 patients enrolled in the control (n = 16) and paclitaxel + pembrolizumab ± SD-101 (n = 27) arms. 12 of 27 patients (44.4%) receiving chemo-immunotherapy experienced increased lymphadenopathy within the first 12 weeks compared to 1 of 16 patients (6.3%) in the control group (p = 0.014). Most patients with increased lymphadenopathy were in the SD101/pembro arm (n = 10, p = 0.002). Increased lymphadenopathy was observed despite concomitant decrease in breast tumor size at all time points. 11 of 12 patients with increased lymphadenopathy had pathologically negative nodes at surgery. There was no association between lymphadenopathy and lower residual cancer burden or immune-related toxicity. CONCLUSIONS: The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery.

Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node-negative, human epidermal growth factor receptor 2-positive breast cancer: A Surveillance, Epidemiology, and End Results population-based study.

BACKGROUND: Persistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking. METHODS: Data on patients with T1cN0M0-stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well-balanced cohorts for the NAT and AT groups. Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT. RESULTS: After PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35-0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37-0.98; p = .041). A logistic regression model revealed that White race and hormone receptor-negative status independently predicted pCR. CONCLUSIONS: For patients with T1cN0M0-stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

OBJECTIVE: To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. METHOD: This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. RESULTS: The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. CONCLUSION: For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

Low back pain characteristics in adolescent patients with early-stage spondylolysis: a prospective study.

PURPOSE: Early-stage spondylolysis (ESS) is a common cause of acute low back pain (LBP) in adolescents. When treating patients with ESS, early diagnosis is essential, yet difficult without magnetic resonance imaging. This study evaluates a self-reported questionnaire for detecting ESS. METHODS: We evaluated a total of 69 adolescents (≤ 18 years old) with acute LBP (≤ 1 month) with plain radiography, magnetic resonance imaging and a questionnaire including the following parameters: exercise frequency per week, daily training time, the necessity for stopping sports activity, pain-producing situations, pain quality, pain response to hyperextension or hyperflexion, pain location, and pain extent. Patients with obvious pathological findings other than ESS (e.g., disk herniation or infection) were excluded. The correlation of each question and gender, regarding ESS was determined, to evaluate the value of the originally developed questionnaire. RESULTS: 24 out of 69 patients were diagnosed with ESS (ESS group), with a mean age of 13.9 years old and 21 males and 3 females in the group. 45 patients had NS-LBP, with a mean age of 14.6 years old, and 28 males and 17 females in the group. Correlation analyses showed weak associations between ESS and higher frequency of exercise per week, longer training time per day, and pain-producing situations. There was also a moderate association between ESS and male gender. CONCLUSION: Exercise frequency, training time, pain-provoking situations, and gender could be important factors to detect ESS within this questionnaire.

Metamodel for Groundwater Leaching Assessment in Europe.

Under Regulation (EC) 1107/2009, FOCUS leaching models forecast the concentration of plant protection product (PPP) active substances in groundwater, known as the predicted environmental concentration (PECGW), based on parameters like DT50, KOC, and application rate. This study used simulated PECGW from PEARL and PELMO for training with over 870 combinations of KOC and DT50 across 174 different crop-location-software scenarios. Generalized additive models (GAMs) were trained on these simulations, achieving 96-99% accuracy for in-sample and out-of-sample validation, comparing the predicted environmental concentration in GAM (PECGAM) with the simulated PECGW relative to the 0.1 µg/L regulatory limit. Our GAM approach offers rapid PEC calculations for numerous substances across 174 scenarios, significantly accelerating early-stage molecule development analogue selection.

MobileNet-V2 /IFHO model for Accurate Detection of early-stage diabetic retinopathy.

Diabetic retinopathy is a serious eye disease that may lead to loss of vision if it is not treated. Early detection is crucial in preventing further vision impairment and enabling timely interventions. Despite notable advancements in AI-based methods for detecting diabetic retinopathy, researchers are still striving to enhance the efficiency of these techniques. Therefore, obtaining an efficient technique in this field is essential. In this research, a new strategy has been proposed to improve the detection of diabetic retinopathy by increasing the accuracy of diagnosis and identifying cases in the initial stages. To achieve this, it has been proposed to integrate the MobileNet-V2 deep learning-based neural network with Improved Fire Hawk Optimizer (IFHO). The MobileNet-V2 network has been renowned for its efficiency and accuracy in image classification tasks, making it a suitable candidate for diabetic retinopathy detection. By combining it with the IFHO, the feature selection process has been optimized, which is essential for identifying relevant patterns and abnormalities related to diabetic retinopathy. The Diabetic Retinopathy 2015 dataset has been used to evaluate the effectiveness of the MobileNet-V2/IFHO model. The study results indicate that the DRMNV2/IFHO model consistently outperforms other methods in terms of precision, accuracy, and recall. Specifically, the model achieves an average precision of 97.521 %, accuracy of 96.986 %, and recall of 98.543 %. Moreover, when compared to advanced techniques, the DRMNV2/IFHO model demonstrates superior performance in specificity, F1-score, and AUC, with average values of 97.233 %, 93.8 %, and 0.927, respectively. These results underscore the potential of the DRMNV2/IFHO model as a valuable tool for improving the accuracy and efficiency of DR diagnosis. Nevertheless, additional validation and testing on larger datasets are required to verify the model's effectiveness and robustness in real-world clinical scenarios.

Risk Factors for Positive Resection Margins in Breast-Conserving Surgery for Breast Cancer-Retrospective Analysis.

The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher's exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer.

Outcome Disparities in Patients with Early-Stage Laryngeal Cancer Depending on Localization, Tobacco Consumption, and Treatment Modality.

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is among most frequent malignancies of the head and neck. Recent oncologic research focusses on advanced rather than on early stages. Thus, we aimed to improve the knowledge concerning prognostic factors and survival in early glottic (GC) and supraglottic cancer (SGC). Methods: We retrospectively investigated patients diagnosed in 2007 to 2020 with stage I or II GC (ICD-10-C32.0) or SGC (ICD-10-C32.1, C32.8 or C32.9). For precise discrimination of GC and SGC, pathology reports about biopsy and definitive excision were closely examined and information on clinical characteristics and risk factors were collected before analyzing patterns of risk factors for overall survival (OS) in multivariate Cox regression analyses (mvCox). Results: The cohort included 220 patients with early GC (n = 183) and SGC (n = 37). The GC patients showed significantly improved 5-year OS compared to SGC patients (83.6% vs. 64.9%; p = 0.004), whereas survival according to UICC stage (I vs. II) was not different (p = 0.177). Surgical resection was superior to definitive radiotherapy (RT) for 5-year OS (p < 0.001). Cumulative tobacco consumption of greater than 10 pack years drastically impaired OS (p = 0.024), especially in patients receiving RT (p < 0.001). Supraglottic localization, smoking, and re-resection after initial R1 status consistently were independent prognostic factors in mvCox. Conclusions: Our cohort of early LSCC patients demonstrates significant negative impact of supraglottic localization, older age, tobacco consumption, poor tumor differentiation, and re-resection on OS. Further research is required as there is still lack of evidence on optimal decision-making and therapeutic strategies.

Initial negative resection margin versus revised negative resection margin in patients who underwent surgery without adjuvant therapy for early-stage oral tongue squamous cell carcinoma.

BACKGROUND: In cases of positive resection margin (RM), re-resection is generally recommended. There has been controversy about the oncologic impact of revised negative RMs after re-resection. The aim of this study was to investigate the oncologic impact of revised negative RM in patients who underwent surgery without adjuvant therapy for early-stage (pT1-2/N0) oral tongue squamous cell carcinoma (OSCC). METHODS: We retrospectively analyzed patients with pT1-2 N0 OSCC who did not receive adjuvant therapy (N=441). These patients were classified into an initial negative RM (R0, n = 380) group and a revised negative RM (R1-R0, n = 61) group. Demographic and clinical data (T stage, tumor length, depth of invasion [DOI], lymphovascular invasion [LVI], perineural invasion [PNI], and recurrence) were compared between the R0 and R1-R0 groups. RESULTS: Age, sex, T stage, DOI, LVI, PNI, and SUVmax were not significantly different between the two groups. Local recurrence was more frequent (P=0.045) in the R1-R0 group (13.1 %) than in the R0 group (5.5 %). Local recurrence-free survival was better in the R0 group than in the R1-R0 group (P=0.046). There was no significant difference in overall recurrence or overall survival. On multivariate analysis, initial positive RM was the independent significant risk factor (hazard ratio, 2.249; 95 % confidence interval, 1.025-4.935; P=0.043) for local recurrence. CONCLUSION: A revised clear RM after initial cut-through margin is a risk factor for local recurrence in early-stage OSCC. Cautious should be considered in early-stage OSCC patients with revised clear RM.

Appropriate Use Criteria (AUC) for Non-Small Cell Lung Cancer in a Central/Ultra-Central Location: Executive Summary of the American Radium Society's Systematic Review and Guidelines.

INTRODUCTION: Definitive radiation therapy is considered standard therapy for medically inoperable early-stage NSCLC. Nevertheless, for patients with tumors located near structures such as the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on managing medically inoperable NSCLC located in a central or ultracentral location relative to critical organs at risk. METHODS: Case variants regarding centrally and ultracentrally located lung tumors were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel. A comprehensive review of the English medical literature was performed from January 1 1946 to December 31 2023 to inform consensus guidelines. Modified Delphi methods were used by the panel to evaluate the variants and procedures, with at least three rating points from median defining agreement/consensus. The guideline was then approved by the ARS Executive Committee and released for public comment per established ARS procedures. RESULTS: The Thoracic ARS AUC Panel identified 90 relevant references and obtained consensus in all variants. Radiotherapy alone was considered appropriate, with additional immunotherapy to be considered primarily in the clinical trial setting. Hypofractionated radiotherapy in eight to 18 fractions was considered appropriate for ultracentral lesions near the proximal tracheobronchial tree, upper trachea, and esophagus. For other ultracentral lesions near the heart, great vessels, brachial plexus, and spine, or for non-ultracentral but still central lesions, five-fraction stereotactic body radiation therapy was also considered an appropriate option. Intensity-modulated radiotherapy was considered appropriate and three-dimensional-conformal radiotherapy inappropriate for all variants. Other treatment planning techniques to decrease the risk of overdosing critical organs at risk were also considered. CONCLUSIONS: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of stage I NSCLC in a central or ultracentral location.

Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data.

INTRODUCTION: Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients' quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan. METHODS: This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups. RESULTS: The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75-0.92, P = 0.0003). CONCLUSIONS: In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM. Graphical abstract available for this article.

Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.

Background: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC). Objective: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival. Design: Cohort study. Methods: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding. Results: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates. Conclusion: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.

Breast-preserving treatment leads to higher 10-year survival in early-stage breast cancer This study compared the long-term survival outcomes of breast-conserving therapy (BCT) and mastectomy for early-stage breast cancer. Analyzing data from over 3400 women diagnosed in 2004, researchers found that BCT recipients had higher 10-year overall and breast cancer-specific survival rates compared with mastectomy recipients. Adjusted models showed a 22% higher risk of all-cause death.

Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis.

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

Quantitative Biomarkers, Genomic Assays, and Demographics Associated with Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER-Negative Breast Cancer.

BACKGROUND: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups. METHODS: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS." Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%. RESULTS: Overall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94-0.97) or PR% (AOR=0.98, 95% CI 0.96-0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04-1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29-0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41-0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01-1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS. CONCLUSIONS: Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS.

Patients With Surgically Resectable Lung Cancer Who Opt for Radiation Have Worse Outcomes.

BACKGROUND: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves. RESULTS: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HRadj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HRadj 4.43; 95% CI: 3.57-5.50, p < 0.001). CONCLUSIONS: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality.

Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario.

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB-IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)-IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.

Sentinel lymph node biopsy in early-stage oral squamous cell carcinoma: A retrospective single-center analysis.

Sentinel lymph node biopsy (SLNB) is increasingly incorporated in European national guidelines for the management of the clinically node-negative neck (cN0) in early-stage oral squamous cell carcinoma (OSCC). In Germany, SLNB in OSCCs is not yet routinely performed. This study aimed to evaluate the clinical outcome of SLNB in a German cohort. Patients with primary early-stage OSCC who underwent tumor resection and SLNB were retrospectively analyzed. Clinical-pathological characteristics were documented. Primary endpoints were sensitivity and the negative predictive value (NPV). A total of 46 patients with a mean age of 62.3 (±14.5) years met the inclusion criteria. Most tumors were located in the tongue (63.0%). Bilateral drainage from a lateral tumor was observed in three cases (6.5%), and sentinel lymph node metastasis was detected in three patients (6.5%). Mean follow-up for all patients was 13.8 months (±9.6). One patient developed regional recurrence following a negative SLNB during the observation period, leading to an NPV of 0.98 and a sensitivity of 75.0%. The 2-year neck-specific relapse-free survival was 92.8%. SLNB in early-stage OSCC is a reliable diagnostic tool of the cN0 neck, ensuring a high NPV and RFS. SLNB can be advantageous in comparison to elective neck dissection due to the detection of contralateral lymph drainage.

LungPath: artificial intelligence-driven histologic pattern recognition for improved diagnosis of early-stage invasive lung adenocarcinoma.

Background: Early-stage invasive lung adenocarcinoma (ADC) characterized by a predominant micropapillary or solid pattern exhibit an elevated risk of recurrence following sub-lobar resection, thus determining histological subtype of early-stage invasive ADC prior surgery is important for formulating lobectomy or sub-lobar resection. This study aims to develop a deep learning algorithm and assess its clinical capability in distinguishing high-risk or low-risk histologic patterns in early-stage invasive ADC based on preoperative computed tomography (CT) scans. Methods: Two retrospective cohorts were included: development cohort 1 and external test cohort 2, comprising patients diagnosed with T1 stage invasive ADC. Electronic medical records and CT scans of all patients were documented. Patients were stratified into two risk groups. High-risk group: comprising cases with a micropapillary component ≥5% or a predominant solid pattern. Low-risk group: encompassing cases with a micropapillary component <5% and an absence of a predominant solid pattern. The overall segmentation model was modified based on Mask Region-based Convolutional Neural Network (Mask-RCNN), and Residual Network 50 (ResNet50)_3D was employed for image classification. Results: A total of 432 patients participated in this study, with 385 cases in cohort 1 and 47 cases in cohort 2. The fine-outline results produced by the auto-segmentation model exhibited a high level of agreement with manual segmentation by human experts, yielding a mean dice coefficient of 0.86 [95% confidence interval (CI): 0.85-0.87] in cohort 1 and 0.84 (95% CI: 0.82-0.85) in cohort 2. Furthermore, the deep learning model effectively differentiated the high-risk group from the low-risk group, achieving an area under the curve (AUC) of 0.89 (95% CI: 0.88-0.90) in cohort 1. In the external validation conducted in cohort 2, the deep learning model displayed an AUC of 0.87 (95% CI: 0.84-0.88) in distinguishing the high-risk group from the low-risk group. The average diagnostic time was 16.00±3.2 seconds, with an accuracy of 0.82 (95% CI: 0.81-0.83). Conclusions: We have developed a deep learning algorithm, LungPath, for the automated segmentation of pulmonary nodules and prediction of high-risk histological patterns in early-stage lung ADC based on CT scans.

A Silent Threat: Deep Vein Thrombosis in Early-Stage Parkinson's Disease.

Introduction: The primary clinical manifestation of venous thrombosis is discomfort in the lower extremities. Some early Parkinson's disease (PD) patients feel discomfort in the lower limbs. Venous thrombosis can risk lives by causing pulmonary embolism. This study examines the incidence of DVT in early PD patients and its correlation with different clinical and lab features. Methods: A cross-sectional study was conducted on 117 patients with early-stage PD. Ultrasonography was employed to detect the presence of DVT. Factors such as age, gender, body mass index, lifestyle habits (smoking and drinking), medical history (hypertension, diabetes, atrial fibrillation, and tumor), and other lab tests linked to thrombosis were analyzed. Results: In 117 patients, 11 (9.4%) had DVT, while 106 (90.6%) did not. There were no significant differences in gender, BMI, habits, medical history, or other thrombosis-related tests between both groups. However, DVT patients were older with higher d-dimer levels. They also showed an increased right substantia nigra ultrasound echo area, higher HY grades, higher UPDRS 3 scores, less improvement in UPDRS 3 scores and levodopa response. Discussion: The primary risk factors for lower extremity venous thrombosis were found to be age, d-dimer levels, and low-dose levodopa. Therefore, for elderly patients with early-stage PD, it is crucial to conduct d-dimer and lower extremity vascular ultrasound tests. The prevention of venous thrombosis in the lower extremities of early PD patients is of utmost importance.