Stage N2 Research Articles

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

Alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients

BackgroundThe alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients is still unclear.MethodsPostsurgical tissues from the enrolled luminal A BCs were divided into five categories: primary BC lesion at stage N0 (PL1), primary BC lesion at stage N1 (PL2), negative axillary lymph node at stage N0 BC (LN1), negative axillary lymph node at stage N1 BC (LN2), and positive axillary lymph node at stage N1 BC (LN3). The frequencies of positive immune markers (CD4, CD8, PD1, PD-L1, T-cell immunoglobulin and mucin domain 3 (TIM3), and forkhead box protein 3 (Foxp3)) in the above tissues were quantified by AKOYA Opal Polaris 7 Color Manual IHC Detection Kit.ResultsA total of 50 female patients with luminal A BC were enrolled in this study. Among these patients, 23 had stage N1 disease, and 27 had stage N0 disease. Compared with that in the PL2 subgroup, the frequency of PD-1-positive cells was significantly greater in the PL1 subgroup, whether at the stromal or intratumoral level (P value < 0.05). Both the frequency of CD8 + T cells in LN1 and that in LN2 were significantly greater than that in LN3 (P value < 0.05). The frequency of TIM3 + T cells in LN1 was significantly greater than that in PL1 (P value < 0.05). The frequency of CD8 + TIM3 + T cells was significantly greater in both the LN2 and LN3 groups than in the PL2 group (P value < 0.05). The frequency of CD4 + Foxp3 + T cells was significantly greater in LN1 than in PL1 (P value < 0.05), which was the same for both LN3 and PL2 (P value < 0.05).ConclusionIncreased frequencies of CD8 + PD1+, CD8 + TIM3 + and CD4 + Foxp3 + T cells might inhibit the immune microenvironment of axillary metastatic lymph nodes in luminal A breast cancer patients and subsequently promote lymph node metastasis.

Vortioxetine’s impact on the autonomic nervous system in depressed children and adolescents: analysis of the heart rate variability

Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug’s multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.

Pharmacologic Sleep Aids in the Intensive Care Unit: A Systematic Review.

Background: Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve sleep, although their benefits in the ICU remain uncertain. This review aims to provide a comprehensive assessment of the objective and subjective effects of medications used for sleep in the ICU, as well as their adverse effects. Methods: PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from their inception until June 2023 for comparative studies assessing the effects of pharmacologic sleep aids on objective and subjective metrics of sleep. Results: Thirty-four studies with 3498 participants were included. Medications evaluated were melatonin, ramelteon, suvorexant, propofol, and dexmedetomidine. The majority of studies were randomized controlled trials. Melatonin and dexmedetomidine were the best studied agents. Objective sleep metrics included polysomnography (PSG), electroencephalography (EEG), bispectral index, and actigraphy. Subjective outcome measures included patient questionnaires and nursing observations. Evidence for melatonin as a sleep aid in the ICU was mixed but largely not supportive for improving sleep. Evidence for ramelteon, suvorexant, and propofol was too limited to offer definitive recommendations. Both objective and subjective data supported dexmedetomidine as an effective sleep aid in the ICU, with PSG/EEG in 303 ICU patients demonstrating increased sleep duration and efficiency, decreased arousal index, decreased percentage of stage N1 sleep, and increased absolute and percentage of stage N2 sleep. Mild bradycardia and hypotension were reported as side effects of dexmedetomidine, whereas the other medications were reported to be safe. Several ongoing studies have not yet been published, mostly on melatonin and dexmedetomidine. Conclusions: While definitive conclusions cannot be made for most medications, dexmedetomidine improved sleep quantity and quality in the ICU. These benefits need to be balanced with possible hemodynamic side effects.

Cardiac substructure radiation dose study of conventional radiotherapy for stage N2-3 non-small cell lung cancer.

e20071 Background: There has been widespread reporting on predictive dose parameters for cardiac substructures in radiotherapy for non-small cell lung cancer (NSCLC). However, most advanced NSCLC patients are staged as N2-3, and there is a lack of research on the dose distribution, dose contribution and prognosis of the heart in conventional radiotherapy for N2-3 stage NSCLC. Methods: Retrospective analysis of 274 patients of stage N2-3 NSCLC treated with radiotherapy (RT) of prescription dose from 60Gy to 70Gy. Experienced radiation oncologists delineated the cardiac substructures. All patients were categorized according to different lymph node irradiation and tumor spatial locations. Spearman and linear regression were used for variation of dose-volume parameters, as well as the impact of different primary tumor locations and irradiated lymph nodes on the parameters of the entire heart and substructures. Receiver operating characteristic (ROC) curves, Kaplan-Meier, and Cox regression were performed on the influencing factors of adverse cardiac events after radiotherapy and prognosis analysis. Results: There are significant differences in the dose-volume parameters of the whole heart and its substructures. Mean heart doses (MHD),and the mean doses (Dmean) for the left atrium, right atrium, right ventricle, left ventricle and the left anterior descending coronary artery (LAD) were 15.7Gy (range 0.2-30.0Gy), 19.7Gy (range 0.3-55.0Gy), 9.7Gy (range 0.3-59.8Gy), 7.9Gy (range 0.1-48.2Gy), 6.4Gy (range 0.1-52.6Gy) and 5.2Gy (range 0.1-45.0Gy), respectively. The left atrium Dmean has the most significant impact on MHD compared to other substructures (B = 0.418, P &lt; 0.05). Dose-volume parameters of the whole heart and the left atrium were positively correlated with the irradiation of the 7th lymph node region (P &lt; 0.05). MHD and left atrium Dmean for tumors located in the lower region were significantly higher than those in the upper region (P &lt; 0.001). Patients with LAD V30 ≥ 26.9% had a significantly higher risk of mortality compared to those with LAD V30 &lt; 26.9% (P = 0.003, HR = 2.883, 95% CI = 1.436-5.788). Conclusions: With the dose distribution differences among the whole heart and its substructures. We observed the base of the heart received the highest dose, the dose to the left atrium is particularly required attention. The irradiation of different lymph nodes and different primary lesions has an impact on the dose variations of different cardiac structures. LAD V30 is an independent influencing factor of overall survival (OS) for N2-3 stage NSCLC. This study provides considerable information for the dose optimization of cardiac substructure in radiotherapy planning for N2-3 stage NSCLC.

Racial disparities in presentation and survival for lobular breast cancer.

1596 Background: We characterized differences in presentation and survival, and identified predictors of survival, among women of varying race with lobular breast cancer. We also assessed if these trends were unique to ILC by comparing with invasive ductal carcinoma (IDC) and mixed invasive ductal-lobular carcinoma (IDLC). Methods: Using the SEER database, we performed a population-based retrospective cohort study of women diagnosed with ILC, IDC, and IDLC between 1998 and 2019. We collected race, age, marital status, and income. Clinical data included grade, size, laterality, clinical stage, receptor status, surgery type, chemotherapy, radiation, and breast-cancer-specific survival (BCSS). Differences between racial groups were assessed using Chi-square tests or one-way ANOVA. To identify predictors of survival, Cox-proportional hazard models were constructed. Statistical analyses were performed using SAS and P values &lt; 0.05 were considered significant. Results: 38,769 women with ILC were identified, including 32,857 White, 2398 Black, 2352 Asian, and 1162 women of other race. Black women presented with higher-grade, advanced clinical stage, ER+ disease, N2-3 stage, and lower rates of unilateral/bilateral mastectomy than White women. Black women were more likely to not undergo surgery (7.13%), compared with White (4.25%) and Asian (4.04%) women ( P = .0001). Asian women were younger, had more ER-/PR- ILC, and received more chemotherapy. The five-year BCSS rates in Black, White, Asian, and women of other race were 91.5%, 94.2%, 93.7%, and 95.7%, respectively ( P&lt; .0001). Predictors of worse survival include Black race (HR 1.32, P &lt; .0001), ER-/PR- (HR 2.18, P&lt; .0001), ER+/PR- (HR 1.52, P&lt; .0001), and no surgery (HR 4.19, P &lt; .0001). Radiotherapy was associated with improved survival (HR 0.82, P &lt; .0001), while chemotherapy did not affect survival (HR 1.1, P= 0.0504). In comparing across breast cancer subtypes, Black women similarly present with higher grade tumors, advanced clinical stage, ER+ disease, and had higher rates of surgery omission in IDC and IDLC. However, ER-/PR- subtype was notably higher in ILC among Asian women compared with IDC, whereas Black women have higher rates of ER+/PR+ and ER-/PR- ILC. Black women had the lowest five-year BCSS rates across all breast cancer subtypes. Predictors of worse survival in IDC and IDLC include Black race and negative hormone receptor status, while radiation therapy was associated with improved survival. Conclusions: There are differences in clinical presentation of invasive lobular breast cancer according to race.Black women had more advanced disease, while Asian women were younger. Across all subtypes, overall survival for Black women at 5 years was worse compared to other racial groups. Our data provides insight into the complex interactions of race, clinical characteristics, and survival outcomes in lobular breast cancer, with implications for screening considerations.

Role of serum α-Klotho level in patients with breast carcinoma.

e15031 Background: The Klotho gene regulates multiple intracellular signalling pathways involving FGF-23, Insulin, IGF1, TGF-β1, Wnt/β-catenin and mammalian targets of rapamycin. The Klotho gene is downregulated in cancer and has a tumour suppressor role. Only a few studies have been done assessing its role in various cancers. None has looked into its association with all the clinicopathological characteristics of Carcinoma breast along with Pathological complete response (PCR). In August 2022, an oral senolytic form of Klotho was identified making it a possible and targetable protein. Methods: This was a Prospective cross-sectional study. Patients with biopsy-proven carcinoma breast who were previously untreated and had no significant past history were included. 84 patients were studied. Serum αKlotho level was estimated before initiating any treatment and its association with clinicopathological characteristics and with PCR was analysed. Results: A total of 84 patients were studied. The mean age was 50.76 years. Amongst our patients 65% were Estrogen Receptor (ER)+, 41.6% HER2+ and 11.9% were TNBC. 11.9% were of T1 stage, 29.8% T2, 19% T3, and 39.3% were T4. 16.7% had N0, 48.8% N1, 14.3% N2 and 20.2% had N3 stage. 20.2% were metastatic (MBC) and 79.8% were non-metastatic. 33.3% had grade 3 tumours, 56% grade 2 and 10.7% had grade 1. 61.9% were treated with NACT. The mean serum αKlotho level was 1.81ng/ml ranging from 0-5.15ng/ml. The αKlotho level was 2.04ng/ml in ER+ and 1.37ng/ml in ER-negative (p 0.011). As the Nottingham grade of the tumour increased from 1 to 3, αKlotho level decreased, with a mean value of 3.54ng/ml in grade 1, 1.71ng/ml in grade 2, and 1.42ng/ml in grade 3 (p 0.001). As the T stage increased from 1 to 4, αKlotho level decreased from 2.6ng/ml to 1.61ng/ml. Patients with N0 had a higher αKlotho of 2.92ng/ml, N1 had 1.64ng/ml, N2 1.79ng/ml, and N3 had 1.31ng/ml (p 0.001). MBC had a lower level of 1.47ng/ml than non-metastatic(1.9ng/ml). αKlotho level negatively correlated with ki67 with a correlation coefficient of -0.2. Among the patients who received NACT, we analysed 36 patients for the correlation with PCR. αKlotho level in patients who attained PCR was 1.58ng/ml and in those who did not attain PCR was 1.64ng/ml which was not significant. Conclusions: Klotho gene is identified to have a tumour suppressor role and its product αKlotho seems to have a protective role in Carcinoma breast. We found that patients with a higher serum αKlotho level had a lower histological grade(p 0.001) and a Node-negative (p 0.001) disease. Non-metastatic patients and patients with lower Ki 67 had high αKlotho levels. However, we could not find any significant association between αKlotho level and PCR. This is the first study with a large sample size done to look at the association of serum αKlotho with clinicopathological characteristics of carcinoma breast and that has found a significant association of αKlotho levels with higher grade and Node-negative disease.

A prospective phase II randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer.

e20004 Background: To investigate the efficacy and safety of folic acid intervention in lung cancer patients with radiation esophagitis caused by concurrent chemoradiotherapy. Methods: It was a randomized, controlled, single-center clinical trial of 82 patients with stage N2~N3 lung cancer including SCLC and NSCLC were prospectively included. All patients were randomly divided into experimental and control group according to 1:1, and patients were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes (More than 2 cycles of chemotherapy were completed during the same period of radiotherapy or take targeted drugs at the same time, the cumulative radiation dose of chest lesions should exceed 40Gy). The experimental group took folic acid tablets 30mg/day orally at the beginning of radiotherapy until the end of radiotherapy, while the control group did not receive any drug intervention.When two groups appeared radiation esophagitis, the grading criteria for RTOG should be evaluated first, then according to the guidelines of symptomatic treatment.Esophageal toxicity was evaluated during radiotherapy, and improved RTOG and NCI-CTC ratings were performed weekly at the onset of radiation esophagitis and thereafter until 1 week after the end of radiotherapy. Results: The incidence of radiation esophagitis in the experimental group was low during the observation period, and the occurrence time of radiation esophagitis could be delayed in the experimental group, but there was no statistical significance between the two groups ( P=0.456). After folic acid intervention, the symptoms of pain and dysphagia of radiation esophagitis in the experimental group were significantly decreased, especially the RTOG grade and NCI-CTC improvement grade decreased significantly 2 weeks after the occurrence of radiation esophagitis( P=0.007, P=0.009). In the experimental group, it was found that the greater the change of hemoglobin before and after radiotherapy, the occurrence time of radiation esophagitis was about delayed, which was statistically significant(r=0.348, P=0.040).The correlation analysis of the control group showed that the change of body mass index was positively correlated with the onset time of radiation esophagitis(r=0.372, P=0.020);The lower the hemoglobin content after radiotherapy and the larger the hemoglobin difference before and after radiotherapy, the higher the highest incidence of radiation esophagitis(r= -0.454, P=0.004;r= -0.343, P=0.032). Conclusions: Oral folic acid can delay the onset of radiation esophagitis due to concurrent chemoradiotherapy and promote the recovery of radiation esophagitis to a certain extent,but can not interfere with the occurrence of radiation esophagitis.This trial is registered in Clinical Trials(NCT0529636). Clinical trial information: NCT0529636 .

Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high/mismatch repair-deficient colorectal cancer: Results from a randomized, open-labeled, phase Ib study.

3505 Background: Immune checkpoint inhibitors have been used in neoadjuvant setting and showed promising clinical benefits in various tumors. Herein, we evaluate IBI310 plus sintilimab as neoadjuvant treatment in patients (pts) with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) colorectal cancer (CRC) in a randomized, open-labeled, phase Ib study. Methods: Previously untreated pts with locally advanced (stage IIB-III), resectable, MSI-H/dMMR CRC were enrolled and randomized to receive 1 cycle of IBI310 1mg/kg plus 2 cycles of sintilimab 200 mg Q3W (arm A) or 2 cycles of sintilimab 200 mg Q3W (arm B) as neoadjuvant treatment. The stratification factors were risk evaluation at baseline (high risk: stage T4 or N2 vs low risk: stage T1-3 and N1) and age ( &lt; 55 years vs ≥55 years). Curative resection was scheduled on day 36 to 56 after first dose of neoadjuvant treatment. Primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection rate and safety. Results: As of February 4, 2024, 101 pts were enrolled (males: 55.4%, median age: 56 years, ECOG PS 1: 54.5%, high risk: 76.2%) and randomized into arm A (n = 52) and arm B (n = 49). In arm A, 1 pt had early termination of treatment (withdrawal). In arm B, 4 pts had early termination of treatment (1 withdrawal, 1 died, 2 continued neoadjuvant sintilimab). Scheduled curative resection were performed in 51 (98.1%) pts in arm A and 45 (91.8%) pts in arm B. Postoperative evaluation revealed mismatch repair-proficient (pMMR) in 1 pt each in arm A and arm B. The pCR rates were 80.0% (40/50, 95%CI: 66.3-90.0) in arm A vs 47.7% (21/44, 95%CI: 32.5-63.3) in arm B (p = 0.0007). All pts received surgery had R0 resection. Median time between first dose of neoadjuvant treatment and surgery was 47 days (range: 35-82). Surgery delay occurred in 3 pts including 2 pts in arm A due to grade 2 hypothyroidism (2 days delay) and grade 1 hyperthyroidism (13 days delay), and 1 pt in arm B for other reason (26 days delay). Treatment-emergent adverse events (TEAEs) occurred in 46 pts (88.5%, grade≥3 in 13 pts) in arm A and 39 pts (79.6%, grade≥3 in 9 pts) in arm B. Immune-related adverse events (irAEs) occurred in 22 pts (42.3%) in arm A and 18 pts (36.7%) in arm B. Grade ≥3 irAEs occurred in 3 pts in arm A, including immune-mediated myocarditis, ileus and enteritis, and in 4 pts in arm B, including alanine aminotransferase increased, rash, hypothyroidism and myocarditis. Serious TRAEs occurred in 4 (7.7%) pts in arm A and 3 (6.1%) pts in arm B. TRAE leading to death occurred in 1 pt in arm B (myocarditis). Conclusions: Neoadjuvant IBI310 plus sintilimab significantly improved pCR rate than sintilimab alone in MSI-H/dMMR CRC. The safety profiles were comparable and manageable in both treatment arms. Clinical trial information: NCT05890742 .

The Incidence of Breast Cancer Lymph Node Involvement in Trinidad and Tobago.

Objective This study aims to investigate breast cancer lymph node involvement in a West Indian population whilecorrelating it with various histological parameters and evaluating the role of the sentinel lymph node biopsy. Method This is a retrospective study where histology reports for all breast cancer-related biopsies from 2018 to 2021, totaling 813 samples, were obtained. Histological parameters from these reports were extracted into a spreadsheet andanalyzed usingStatistical Product and Service Solutions (SPSS, version 28.0; IBM SPSS Statistics for Windows, Armonk, NY) software for TNM staging and axillary and sentinel lymph node dissections, among other fields found in histology reports. Results In 44.8% of cases, patients present at the T2 stage with associated lymph node spread. Each T stage had more lymph nodes involved than uninvolved for tumors sized T2 and higher. Inversely, for tumors staged under T2, there were generally more uninvolved lymph nodes than involved ones. Larger tumors were found to have advanced N staging, especially in the T3 category, where a significantly higher proportion of cases were found to have N2 and N3 staging compared to the other T stages. This trend is also seen in M staging, where larger tumors metastasize more than smaller tumors (40% for T4a, 0% for T1). Despite significant lymph node involvement being observed, sentinel lymph node biopsies were usually negative. Conclusion More patients in this population present with lymph node involvement than without. Larger breast cancer tumors are associated with greater lymph node involvement, particularly at T2 and higher stages. Sentinel lymph node biopsies can be omitted in smaller breast cancer tumors up to 2 cm in size, and the local recurrence rate is low despite a false-negative rate of around 10% in upfront sentinel lymph node biopsy.

A comparative study on quality of life of patients with breast cancer receiving subcutaneous gland resection combined with primary prosthesis implantation: Minimally invasive versus open surgery.

e12597 Background: Subcutaneous gland resection of the breast combined with primary prosthesis reconstruction is mostly used for reconstruction of early breast cancer (EBC) patients. In this study, we compared the long-term quality of life (QOL) of patients who underwent these procedures in a minimally invasive or open approach. Methods: The baseline data of EBC patients who underwent subcutaneous gland resection of breast combined with primary prosthesis reconstruction in a minimally invasive or open approach from 2008 to 2020 were retrospectively analyzed. The patients receiving minimally invasive surgery were regarded as minimally invasive group, and open surgery were regarded as open group. The BREAST-Q questionnaires were used to evaluate patients’ satisfaction with breasts, implants, animation deformity, psychosocial well-being, sexual well-being, physical well-being (chest) and breast sensation. Results: A total of 546 patients were enrolled, patients with local and regional recurrence, distant metastasis, death and prosthesis (44, 44, 22,12, respectively) were excluded, 423 patients were given questionnaires to evaluate their quality of life. Totally 226 questionnaires were recovered, with a response rate of 53.43%. Except 5 questionnaires with incomplete answers, 221 questionnaires were finally valid. There were 105 cases in the minimally invasive group, with an average follow-up time of 107.48 months (range 39-185 months), and 115 cases in the open group, with an average follow-up time of 77.97 months (range 36-188 months). The age was 43.0 [37.0, 47.0] years in all patients, 43.0[38.0, 47.0] years in the minimally invasive group and 42.5[36.8, 47.0] years in the open group. The patients in stage T1-2 accounted for 96.19% in the minimally invasive group and 97.42% in the open group, stage N0-1 accounted for 90.48% and 93.97, respectively. Prosthetic implant size showed no significant difference between two groups (220 [180, 240] cm3 vs 200 [180, 245] cm3, p=0.083). No significant difference was observed in patients’ race, education, marital status, income, job and breast size between the two groups ( p&gt;0.05). The scores of the minimally invasive group in satisfaction with breasts (54.0 [47.0, 59.0] vs 49.0 [44.8, 55.0], p&lt;0.01), animation deformity (70.0 [59.0, 100.0] vs 62.0 [57.0, 84.0], p=0.016), psychosocial well-being (66.0 [53.0, 93.0] vs 62.0 [49.0, 83.0], p=0.027), and physical well-being(chest) (48.0 [32.0, 56.0] 42.0 vs [32.0, 52.0], p=0.038) were significantly higher compared with the open group. There was no significant difference in implants, sexual well-being and breast sensation between the two groups. Conclusions: Minimally invasive subcutaneous gland resection combined with primary prosthetic implantation may improve postoperative quality of life in patients with EBC.

Neoadjuvant/adjuvant pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo for gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: Major pathologic response (mPR) in KEYNOTE-585.

4073 Background: Pathologic tumor downstaging (pDS) is more accurate than clinical staging for prognosis; generally, patients (pts) with downstaged tumors have lower recurrence rates and improved overall survival (OS). mPR is an important surrogate end point in non–small cell lung cancer, but data are scarce in gastric cancer. In the randomized phase 3 KEYNOTE-585 trial (NCT03221426), neoadjuvant or adjuvant pembro + chemo (cisplatin + capecitabine [XP] or cisplatin + 5-fluorouracil [FP]) was not superior to pbo + chemo (XP or FP) for event-free survival (EFS) in the intention-to-treat (ITT) population of pts with locally advanced G/GEJ adenocarcinoma; pembro + chemo significantly improved pathologic complete response (pCR) vs pbo + chemo (difference, 10.9%; 95% CI, 7.5-14.8; P&lt;0.00001). In this post hoc analysis we examined the utility of mPR and pDS as surrogate end points in KEYNOTE-585. Methods: Pts with untreated localized G/GEJ adenocarcinoma (including Siewert type 2 or 3 tumors) and ECOG PS 0 or 1 who planned to undergo surgery after preoperative chemo were eligible. The main cohort of KEYNOTE-585 received pembro or pbo + XP or FP; the safety cohort received pembro or pbo + docetaxel, oxaliplatin, FP, and leucovorin (FLOT). Objectives for the post hoc analysis were the relation between mPR (≤10% residual viable tumor, comparable to Mandard tumor regression grade 1 or 2) and EFS per RECIST v1.1 per investigator and OS, plus the percentage of pts who had improved survival, by stage, compared with downstaging in the pTNM group. Overall downstaging was derived by comparing answers to questions regarding primary tumor and nodal involvement from clinical and pathologic assessments for each pt. Pts could have tumor downstaging, nodal downstaging, or both. If both, the number of levels downstaged for tumor and nodes were added together to calculate a total number of levels downstaged. The database cutoff was February 9, 2023. Results: A total of 1007 pts were analyzed (n=502, pembro + chemo; n=505, pbo + chemo); 44.0% and 34.1%, respectively, had pathologic nodal stage N0. The incidence of mPR (grade 1/2 tumor regression) was 31.5% with pembro + chemo vs 22.2% with pbo + chemo. In pts who had mPR, the HRs (95% CI) for EFS and OS were 0.6 (0.4-1.0) and 0.7 (0.4-1.2), respectively, for pembro + chemo vs pbo + chemo. Downstaging results are shown (Table). Conclusions: In this post hoc analysis, pts with mPR had numerically improved PFS and OS with pembro + chemo vs pbo + chemo; these findings were consistent with analysis of the ITT population. Further studies in this population are warranted. Clinical trial information: NCT03221426 . [Table: see text]

A Novel Continuous Sleep State Artificial Neural Network Model Based on Multi-Feature Fusion of Polysomnographic Data.

Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency. The study involved 50 normal and 100 obstructive sleep apnea-hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM). The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%. A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.

Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.

6009 Background: E3311 is a phase II trial of TOS by credentialed surgeons with pathology-driven deintensified post-operative management in HPV+ OPC. Intermediate risk patients were randomized between standard and reduced dose radiation. We present mature outcome data, at median follow up of 52.4 months (m). Methods: Patients were eligible who had resectable cT1-2 stage III/IV AJCC7 p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (Arm A, N=38); those with clear margins, 2-4 + LN, or ENE ≤1mm were randomized to 50Gy (Arm B, N=100) or 60Gy (Arm C, N=108); those with involved margins, &gt;4 + LN, or &gt;1mm ENE received weekly cisplatin 40 mg/m2 and 60-66Gy (Arm D, N=113). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using a log-rank test, stratified by arm for comparisons of primary site and smoking history. Results: Among 359 evaluable patients, 54-m PFS and OS were 90.6% (90% CI: 87.2%, 93.1%) and 95.3% (90% CI: 93.0%, 96.9%). 54-m PFS by arm was: A 93.2% (90% CI: 79.6%, 97.8%); B 94.9% (90% CI: 89.7%, 97.5%); C 90.2% (90% CI: 82.7%, 94.6%) and D 85.5% (90% CI: 77.5%, 90.8%). 54-m OS by arm was: A 97.1% (90% CI: 85.7%, 99.4%); B 97.9% (90% CI: 93.5%, 99.3%), C 95.1% (90% CI: 90.1%, 97.6%) and D 92.5% (90% CI: 86.9%, 95.7%). Among patients in Arm A, 11 had N0 and 27 N1 stage. Median Arm A lymph node yield (LNY) was 29 (11 to 91 LN) and did not differ for patients with/without recurrence (p=0.83). All Arm A recurrences were in N1 patients: 1 at 18 m and 3 at &gt; 40 m. No significant difference in PFS or OS was observed by prescribed radiation dose for intermediate risk patients (Arm B vs. C). Outcome did not differ by primary site of tonsil vs. other OPC (oOPC): 54-m PFS Tonsil 89.3% (90% CI: 84.9%, 92.5%) vs. oOPC 92.9% (90% CI: 87.0%, 96.2%), p=0.28, and 54-m OS Tonsil 94.6% (90% CI: 91.5%, 96.6%) vs oOPC 96.6% (90% CI: 92.4%, 98.5%), p=0.35. Smoking history also did not impact outcome. 54-m PFS was 89.9% (90% CI: 85.9%, 92.9%) for those with ≤10 pack-years (PY) tobacco exposure and 91.7% (90% CI: 83.9%, 95.9%) for those with &gt;10 PY. Conclusions: TOS, neck dissection with deintensified risk-based post-operative management results in outstanding 54-m PFS and OS across all subsites of T1-2 p16+ OPC, irrespective of smoking history. Late recurrence is not increased when post-operative radiation is reduced from 60 to 50Gy for intermediate risk patients. Pathologic &gt;1mm ENE (N=87), involved margin (N=12) or &gt;4 involved LN (N=30) accurately identify patients at increased recurrence risk and outcomes were favorable among such patients. Among patients with favorable pathologic characteristics, a subset with N1 disease are at risk for late recurrence and further characterization of these patients is warranted. Clinical trial information: NCT01898494 .

Outcomes of Patients Undergoing Segmentectomy for Occult Node-Positive Clinical Stage IA Lung Cancer

BackgroundResults of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown. MethodsClinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS). ResultsOf 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray’s P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups. ConclusionsPatients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance.

Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Large muscle group movements during sleep in restless leg syndrome: neurophysiological and clinical implications.

Recently, criteria have been drawn up for large muscle group movements during sleep (LMM), defined as movements lasting for 3-45 seconds in adults, which are often accompanied by changes in sleep stage, arousals, and increases in heart rate. The aim of this study was to characterize LMM in restless legs syndrome (RLS) in order to better evaluate their impact on the neurophysiology of the disorder and, therefore, the possible clinical implications. Consecutive, drug-free patients diagnosed with RLS and controls, aged 18 years or more, were retrospectively enrolled. Leg movement activity-short-interval (SILMS), periodic (PLMS), and isolated (ISOLMS) leg movements during sleep-and LMM were detected and scored. In total, 100 patients and 67 controls were recruited. All movement measures were significantly higher in RLS. A significant positive correlation was found between LMM and ISOLMS index but not PLMS index in both groups. LMM index showed a significant negative correlation with total sleep time, sleep efficiency, and percentage of sleep stages N3 and R, as well as a significant positive correlation with the number of awakenings, and percentage of sleep stages N1 and N2 only in patients with RLS. No significant correlation was found between either LMM or PLMS index and RLS severity. Different types of movements, including SILMS, ISOLMS, and LMM, play somewhat distinct roles in sleep neurophysiology in RLS. Notably, LMM, a newly recognized category of movements, demonstrates associations with sleep architecture instability and fragmentation, arousals, and awakenings, suggesting potential clinical implications.

The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age

PurposeTo determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years.MethodsData of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT).ResultsMedian follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072).On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality.ConclusionFor patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

Exploring dietary differences among developmental stages of triatomines infected with Trypanosoma cruzi in different habitats

Chagas disease affects millions of people in Colombia and worldwide, with its transmission influenced by ecological, environmental, and anthropogenic factors. There is a notable correlation between vector transmission cycles and the habitats of insect vectors of the parasite. However, the scale at which these cycles operate remains uncertain. While individual triatomine ecotopes such as palms provide conditions for isolated transmission cycles, recent studies examining triatomine blood sources in various habitats suggest a more intricate network of transmission cycles, linking wild ecotopes with human dwellings. This study aims to provide further evidence on the complexity of the scale of Trypanosoma cruzi transmission cycles, by exploring the different blood sources among developmental stages of infected triatomines in different habitats. We evaluated infection rates, parasite loads, feeding sources, and the distribution of Rhodnius prolixus insects in Attalea butyracea palms across three distinct habitats in Casanare, Colombia: peridomestics, pastures, and woodlands. Our results show that there is no clear independence in transmission cycles in each environment. Analyses of feeding sources suggest the movement of insects and mammals (primarily bats and didelphids) among habitats. A significant association was found between habitat and instar stages in collected R. prolixus. The N1 stage was correlated with pasture and woodland, while the N4 stage was related to pasture. Additionally, adult insects exhibited higher T. cruzi loads than N1, N2, and N3. We observed higher T. cruzi loads in insects captured in dwelling and pasture habitats, compared with those captured in woodland areas. Effective Chagas disease control strategies must consider the complexity of transmission cycles and the interplay between domestic and sylvatic populations of mammals and vectors.

Prognostic value of sarcopenia in the patients with locally advanced nasopharyngeal carcinoma.

Sarcopenia, characterized by loss of muscle mass index (SMI), serves as a diagnostic indicator for malnutrition and has been shown to influence cancer treatment outcomes. The objective of this study was to investigate the prognostic significance of sarcopenia on the locally advanced nasopharyngeal carcinoma (laNPC) patients. 545 patients with stage III-IVa NPC were included in this retrospective study. Sarcopenia was defined using the skeletal muscle index (SMI) determined at the C3 level based on baseline MRI. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). The results of the multivariate analysis revealed that sarcopenia group (HR = 2.82, 95% CI 1.96-4.06, P < 0.01), T4 stage (HR = 1.64, 95% CI 1.24-2.15, P < 0.01), N3 stage (HR = 1.91, 95% CI 1.52-2.40, P < 0.01), comorbidities (HR = 2.08, 95% CI 1.45-2.97, P < 0.01), and any adverse event grade 3-4 (HR = 1.48, 95% CI 1.04-2.01, P = 0.03) were identified as independent risk factors that significantly impacted the OS. Additionally, sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), T4 stage (HR = 1.50, 95% CI 1.17-1.92, P < 0.01), N3 stage (HR = 1.80, 95% CI 1.46-2.22, P < 0.01), sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), and any adverse event grade 3-4 (HR = 1.45, 95% CI 1.04-2.01, P = 0.03) were found to have a significant impact on PFS. Sarcopenia was identified as a prognostic factor for patients with laNPC. Furthermore, T stage, N stage, comorbidities, and any adverse event grade 3-4 were identified as independent prognostic factors for laNPC.