Stage N2 Research Articles

Safety and tolerability of different total neoadjuvant therapy strategies in patients with locally advanced rectal cancer.

121 Background: Total neoadjuvant therapy (TNT) leads to improved local control and organ preservation for locally advanced rectal cancer (LARC). The chemotherapy part of TNT may play a critical role in achieving local control and in improving OS. Few studies have focused on the toxicity associated with the chemotherapy of TNT. Furthermore, the differences in safety and tolerability between radiotherapy-first and chemotherapy-first strategies remain unclear. Methods: LARC patients treated with TNT between June 2020 and July 2023 at a single cancer institute were retrospectively enrolled. TNT consisted of induction chemotherapy followed by long-course chemoradiotherapy (INCT-LC-CRT) or long-course chemoradiotherapy/short-course radiotherapy followed by consolidation chemotherapy (LC-CRT-CNCT/SC-RT-CNCT). Concurrent chemotherapy in LC-CRT was capecitabine (825 mg/m 2 oral twice daily). INCT/CNCT consisted of six cycles of CAPOX (capecitabine 1000 mg/m² oral twice daily on days 1–14 and oxaliplatin 130 mg/m² intravenously on day 1 every 21 days). INCT allowed the addition of bevacizumab (7.5 mg/kg intravenously on day 1). We compared adverse events (AEs) and treatment exposure between INCT-LC-CRT, LC-CRT-CNCT and SC-RT-CNCT. Results: A total of 93 patients were included. Patients with INCT-LC-CRT and LC-CRT-CNCT/SC-RT-CNCT were 28 (30.1%) and 45 (48.4%)/20 (21.5%), respectively. Patients who were treated with INCT-LC-CRT (53.6%) had more N2 stage than those with LC-CRT-CNCT/SC-RT-CNCT (21.6%). Grade 3–4 AEs during chemotherapy were significantly more frequent in LC-CRT-CNCT/ SC-RT-CNCT group than in INCT-LC-CRT group (50.8% vs. 21.4%; p = 0.02). Neutropenia was the most common Grade 3–4 AEs during chemotherapy in INCT-LC-CRT group (7.4%) and LC-CRT-CNCT/SC-RT-CNCT group (27.7%). Grade 3–4 AEs during chemotherapy were not significantly different between the LC-CRT-CNCT and SC-RT-CNCT groups (36.9% vs. 40.0%; p = 0.42). All patients underwent the full radiation dose. The completion rate of six cycles of chemotherapy was no significant difference between INCT-LC-CRT group and LC-CRT-CNCT/SC-RT-CNCT group (92.9% vs. 84.6%; p = 0.37). However, LC-CRT-CNCT/SC-RT-CNCT group required significantly more dose modification during chemotherapy than INCT-LC-CRT group (75.4% vs. 46.4%; p < 0.01). Dose modification during chemotherapy between LC-CRT-CNCT and SC-RT-CNCT group was no significant difference (modification rate 77.8% vs. 70.0%; p = 0.54). Chemotherapy discontinuations due to AEs in INCT-LC-CRT group and LC-CRT-CNCT/SC-RT-CNCT group were 1(3.6%) and 6 (9.2%), respectively. Conclusions: Grade 3–4 AEs during chemotherapy were more frequent and required dose modification of chemotherapy in a radiotherapy-first strategy. Safety and tolerability of chemotherapy part of TNT may differ between radiotherapy-first and chemotherapy-first strategies.

The influence of transcranial alternating current stimulation on EEG spectral power during subsequent sleep: A randomized crossover study.

To evaluate the instant impact of transcranial alternating current stimulation (tACS) on sleep brain oscillations. Thirty-six healthy subjects were randomly assigned to receive tACS and sham stimulation in a crossover design separated by a one-week washout period. After stimulation, a 2-h nap polysomnography (PSG) was performed to obtain Electroencephalogram (EEG) data and objective sleep variables, and self-reported subjective sleep parameters were collected at the end of the nap. EEG spectral analyses were conducted on the EEG data to obtain the absolute and relative power for each sleep stage during the nap. The associations between power values and objective and subjective measurements were analyzed using Spearman or Pearson correlation coefficients. The tACS group presented higher power in slow wave activity (SWA) and delta frequency bands and lower alpha, sigma and beta power values compared to the sham group during the N2 and N3 sleep stages. SWA and delta power were positively associated with sleep duration and sleep efficiency relevant parameters; while alpha, sigma and beta power were positively associated with prolonged sleep latency and wakefulness related variables. PSG, self-reported and sleep diary measured objective and subjective sleep parameters were comparable between the tACS and the sham groups. Our results support that tACS could promote sleep depth in microstructure of sleep EEG, manifesting as an increase in EEG spectral power in low frequency bands and a decrease in high frequency bands. The registration number of this study is ChiCTR2200063729.

Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702.

LBA14 Background: CALGB/SWOG 80702 previously showed that the addition of celecoxib to standard adjuvant chemotherapy with FOLFOX did not significantly improve disease-free survival (DFS) in patients with stage III colon cancer. Here, we evaluated the prognostic and predictive value of ctDNA in identifying a subpopulation of patients who may benefit from celecoxib. Methods: In the subset of patients with adequate biospecimens who participated in CALGB/SWOG 80702, a randomized phase III trial of 3 versus 6 months of adjuvant 5-FU, leucovorin, oxaliplatin (FOLFOX) +/- celecoxib, ctDNA assessment was performed using a clinically validated, tumor-informed 16-plex mPCR-NGS assay (Signatera(TM), Natera, Inc.) after surgery and before the start of adjuvant therapy (baseline). The Kaplan-Meier method was used to describe the distribution of survival time based on ctDNA positivity and log-rank testing was performed. Cox proportional hazards models were used to examine unadjusted associations between ctDNA positivity and disease-free (DFS) and overall survival (OS). Two-sided P values equal to or less than 0.05 were considered statistically significant, except for interaction P values (tested with a likelihood ratio). Results: In total, 1,011 of the 2,526 patients who participated in 80702 had ctDNA testing results from baseline; 189 were ctDNA positive (18.7%). ctDNA positivity associated with male sex, higher T stage, and N2 (versus N1) stage. ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR] 6.52 [95% confident interval (CI) 5.09-8.34; p<0.0001] and OS (HR 6.28 [95% CI 4.63-8.51; p<0.0001]). Three-year DFS was 86.6% in ctDNA-negative cases and 36.8% in ctDNA-positive cases. Among patients who were ctDNA negative, celecoxib use was not significantly associated with worse DFS as compared to placebo (HR 0.75 [95% CI 0.54-1.05; p=0.095]) with a three-year DFS of 87.7% versus 85.5%, respectively. Among ctDNA-positive patients, celecoxib significantly improved DFS compared to placebo (HR 0.59 [95% CI 0.42-0.85; p=0.004]) with a three-year DFS of 44.1% versus 26.6% (P interaction = 0.25). Similar results were seen for overall survival with a hazard ratio of 0.86 (95% CI 0.56-1.33; p=0.49) for ctDNA negative cases and 0.63 (95% CI 0.41-0.96; p=0.028) for ctDNA-positive cases for celecoxib versus placebo (P interaction = 0.28). Conclusion: In a randomized phase III adjuvant therapy trial for stage III colon cancer, ctDNA was highly prognostic of DFS and OS. ctDNA positivity also appeared predictive of the benefit of adjuvant celecoxib for DFS and OS. These results suggest a potential role for ctDNA in determining which patients should consider celecoxib in addition to standard FOLFOX adjuvant therapy. Clinical trial information: NCT01150045 .

The role of lymph node level ratio in predicting prognosis and the benefits of postoperative radiotherapy in patients with pathological N1 stage head and neck squamous cell carcinoma.

To analyze the role of lymph node level ratio (LNLR) in predicting prognosis and the benefits of postoperative radiotherapy (PORT) in patients with pathological N1 (pN1) head and neck squamous cell carcinoma (HNSCC). Patients with pN1 HNSCC from January 2011 to February 2021 were included. Patients were grouped by the LNLR, lymph node yield (LNY), and lymph node ratio (LNR) and were analyzed with the Kaplan-Meier method and multivariate Cox model. This study identified 310 patients. Time-dependent receiver operating characteristic analyses showed superior prognostic ability for LNLR in comparison with LNY and LNR. Patients with an LNLR ≤ 5.25 had the worst survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a higher concordance index for the LNLR model versus the LNY and LNR models. The HRs (95% confidence interval) for a LNLR ≤ 5.25 were 2.46 (1.71-3.54, p<0.001) for DFS, 1.95 (1.38-2.75, p<0.001) for OS, 2.25 (1.53-3.29, p<0.001) for DSS. Furthermore, postoperative radiotherapy-related significant improvement in survival was observed exclusively in the LNLR ≤ 5.25 subgroup. The LNLR is a more robust quality indicator for neck dissection. An LNLR of≤5.25 significantly compromises survival and indicates the need for PORT in patients with pN1 HNSCC.

Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study (UNION TNT).

192 Background: We have demonstrated that neoadjuvant SCRT followed by PD-1 inhibitor plus CAPOX for LARC patients (pts) showed a higher pCR rate and a well-tolerated safety profile in phase III UNION study. Fruquintinib is a potent and highly selective VEGFR inhibitor, which had been approved for previously treated mCRC pts. This study aimed to investigate the efficacy and safety of SCRT followed by fruquintinib plus adebrelimab and CAPOX as a total neoadjuvant therapy for high-risk LARC pts. Methods: In this prospective, open-label, multi-centers, single-arm phase 2 study (NCT06234007), pts diagnosed with newly diagnosed and high risk LARC were recruited. Pts received SCRT (25Gy/5f) followed by six cycles of fruquintinib (4mg, qd, po, q3w,for the initial 6 pts in the safety run-in period, dosage would be adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Primary endpoint was CR rate (including clinical CR &amp; pathologic CR). Secondary endpoints included 3-year EFS rate, OS, R0 resection rate and safety. Results: As of 30 Aug 2024, 45 pts were enrolled (median age 59 years [range: 24-75], 26 males, 23 clinical T4 stage and 20 clinical N2 stage, 36 with EMVI positive, 31 with MRF positive, 22 tumor located ≤5cm from the anal verge). Up to 20 Sep 2024, all pts completed SCRT, 73.33% (33/45), 57.78% (26/45) and 31.11% (14/45) pts completed two, four and six cycles of combination therapy, respectively. At data cut-off, of 33 pts included in the efficacy analysis, 28 pts underwent MRI examination and mrTRG results were available, the remaining 5 pts had early surgery due to AEs/serious AEs. 35.7% (10/28) and 46.43% (13/28) pts were classified as mrTRG1 and mrTRG2, respectively. Of 19 pts who underwent surgery, R0 rate was achieved in all 19 pts (100%) and pCR was achieved in 12 pts (63.16%). Moreover, 1 pt achieved cCR during neoadjuvant therapy, thus the treatment strategy provided a CR rate of 65% (1 cCR plus 12 pCR divided by 20). Grade 3/4 adverse effects (AEs) occurred in 16 pts (47.06%), and most commonly were lymphocyte count decreased (n=6, 18.18%), diarrhea (n=5, 15.15%) and AST increased (n=2, 6.06%). 4 serious AEs reported with intestinal perforation and all achieved pCR after surgery therapy. No treatment related death was reported. Conclusions: SCRT followed by fruquintinib combined with adebrelimab and CAPOX as a total neoadjuvant therapy showed promising CR rate and favorable pCR for high-risk LARC pts, and the safety profile was generally manageable. This treatment strategy might be a potential option as neoadjuvant therapy for high-risk LARC pts. Updated data will be presented in the future. Clinical trial information: NCT06234007 .

Comparative analysis of induction chemotherapy followed by chemoradiotherapy and concurrent chemoradiation therapy efficacy in patients with locally advanced head and neck squamous cell cancer

Treatment strategy of advanced unresectable head and neck squamous cell cancer (HNSCC) is limited to induction chemotherapy (ICT) followed by (chemo) radiotherapy (cRT) and concurrent chemoradiotherapy (CCRT). However, the role of ICT remains controversial considering the lack of overall survival benefit.The aim: to evaluate the role of induction chemotherapy in the treatment of locally advanced HNSCC.Methods: We performed a retrospective clinical study that included patients (pts) with unresectable stage III–IVa cancer of larynx, oropharynx and hypopharynx.Results: A total of 176 pts were enrolled, 84 (48 %) received CCRT with cisplatin or carboplatin and 92 (52 %) — ICT followed by cRT. Groups were well balanced by sex, tumor site, T-stage, while in group of ICT there was a significant prevalence of younger pts (p = 0.004) and pts with stage N2–3 (p = 0,03).The objective response rates (ORR) were 76 % (42 / 55) in CCRT arm (including 53 % (12 / 62) of complete responses) and 72 % (56 / 78) in ICT arm with complete response rate of 15 % (12 / 78). The ORR in ICT arm increased after the completion of CCRT up to 82 % with 53 % (33 / 62) of complete responses. The difference was not statistically significant (p = 0,7).With a median follow-up duration of 8.7 months median progression-free survival (mPFS) was 7.6 and 9.4 months (Hazard ratio (HR) 0.67, 95 % CI 0.43–1.04); 6month OS was 65.7 % and 92.8 % in CCRT and ICT groups, respectively (HR 0.51, 95 % CI 0.30–0.85, р &lt; 0.01).Propensity score matching analysis proved the 6month OS in the ICT + cRT group to be significantly longer than in CCRT group — 97.7 % vs 66.8 %, respectively (HR = 0.28, 95 % CI 0.13–0.62, p &lt; 0.01).Conclusions: ICT + сRT resulted in improvement of PFS and OS compared to CCRT in pts with locally advanced HNSCC.

Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification

Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent need for more accurate stratification schemes. Currently, the TNM staging system is predominantly used in clinical practice for prognostic evaluation, but its accuracy is constrained by the reliance on physician experience. Although biomarker discovery based on molecular pathology offers a new perspective for prognostic assessment, its dependence on expensive gene panel testing limits its widespread clinical application. Pathological images contain abundant diagnostic information, providing a new avenue for prognostic evaluation. In this study, we employed advanced Hover-Net technology to accurately quantify the abundance of epithelial cells, lymphocytes, macrophages, and neutrophils from pathological images, and delved into the clinical and biological significance of these cellular abundances. Our research findings reveal that, in contrast to patients classified as N0 stage, those belonging to the N1 stage demonstrated a marked elevation in the infiltration of epithelial cells, lymphocytes, macrophages, and neutrophils. Notably, the infiltration patterns of lymphocytes and neutrophils exhibited an inverse relationship with the activation status of numerous pivotal gene pathways, including the HALLMARK_HEME_METABOLISM pathway. Furthermore, our analysis distinguished FABP7 as a prognostic biomarker, exhibiting pronounced differential expression between patients with high and low levels of neutrophil infiltration, indicate that cellular abundance analysis based on pathological images can provide a more accurate and cost-effective prognostic evaluation, offering new strategies for the clinical management of lung adenocarcinoma.

Prognostic significance of three lymph node staging systems in pancreatic cancer with ≤ 12 and > 12 retrieved lymph nodes.

This study aimed to evaluate and compare the predictive performance of negative lymph nodes (NLN), lymph node ratio (LNR), and N stage in pancreatic ductal adenocarcinoma (PDAC) among patients with ≤ 12 retrieved lymph nodes and those with > 12 retrieved lymph nodes. Moreover, the association between the three nodal staging systems and survival was also explored. Clinical data on patients diagnosed with PDAC between 2004 and 2020 were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression was performed to identify independent predictors of cancer specific survival (CSS) and overall survival (OS). Survival probability was calculated and compared by the Kaplan-Meier method and log rank test. Akaike information criterion (AIC) and Harrell's C-index were used to evaluate the prognostic ability of each nodal staging system. All three lymph node staging systems were independent predictors of CSS and OS. A higher NLN, a lower N stage, and a lower LNR were associated with improved survival. Compared with N stage, LNR staging performed better with a lower AIC and higher C-index for predicting the prognosis regardless of the sufficiency of retrieved lymph nodes, while NLN staging performed poorly in both the training and validation set. Subgroup analyses showed that the NLN successfully predicted survival outcomes in both lymph node-positive and node-negative patients. LNR demonstrated better predictive performance in PDAC patients regardless of the sufficiency of retrieved lymph nodes. Notably, for stage N0 disease, NLN was a more important prognostic predictor. The combination of LNR and NLN may offer more precise information on lymph node staging than the current staging system.

Mobile Sleep Lab: Comparison of polysomnographic parameters with a conventional sleep laboratory.

In remote areas, visiting a laboratory for sleep testing is inconvenient. We, therefore, developed a Mobile Sleep Lab in a bus powered by fuel cells with two sleep measurement chambers. As the environment in the bus could affect sleep, we examined whether sleep testing in the Mobile Sleep Lab was as feasible as in a conventional sleep laboratory (Human Sleep Lab). We tested 15 healthy adults for four nights using polysomnography (the first two nights at the Human Sleep Lab or Mobile Sleep Lab with a switch to the other facility for the next two nights). Sleep variables of the four measurements were used to assess the discrepancy of different places or different nights. No significant differences were found between the laboratories other than the percentage of total sleep time in stage N3. Next, we analyzed the intraclass correlation coefficient to evaluate the test-retest reliability. The intraclass correlation coefficient between these two measurements: the Human Sleep Lab and Mobile Sleep Lab showed similar reliability for the same sleep variables. The intraclass correlation coefficient revealed that several sleep indexes, such as total sleep time, sleep efficiency, wake after sleep onset, percentage of stage N1, and stage R latency, showed poor reliabilities (<0.5) based on Koo and Li's criteria. In contrast, the percentage of stage N3 showed moderate (0.5-0.75) or good (0.75-0.9) reliabilities. As almost all sleep variables showed no difference and same level of test-retest reliability between the Mobile Sleep Lab and Human Sleep Lab, the Mobile Sleep Lab might be suitable for conducting polysomnography as a conventional sleep laboratory. The reduction in N3 in the Mobile Sleep Lab should be scrutinized in the larger sample, including sleep disorders. Practical application of the Mobile Sleep Lab can transform sleep medicine in remote areas.

The choice of adjuvant radiotherapy in pancreatic cancer patients after up-front radical surgery.

The role of adjuvant radiotherapy in pancreatic cancer following radical surgery remains a subject of of controversy. This study aimed to more accurately screen pancreatic patients who benefit from adjuvant radiotherapy. Clinicopathologic characteristics of patients with resectable pancreatic cancer were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Univariate and multivariate analyses were applied to identify prognostic factors affecting patient survival. All the patients were divided into two groups, one receiving radiation and the other not. Selection bias were reduced by propensity-score matching (PSM). Kaplan-Meier analysis was used to estimate overall survival (OS) and cancer-specific survival (CSS) between the two groups. Within 7097 patients, 2276 received adjuvant radiotherapy (external beam radiation), and 4821 did not. Multivariate analysis revealed that race, age, median income, sex, year of diagnosis, American Joint Committee on Cancer (AJCC) T stage, N stage, scope region lymph surgery, chemotherapy, and radiotherapy were independent predictors for overall survival of all the patients (all p < 0.05). After PSM, a total of 4304 patients were included. There was no OS and CSS benefit of radiotherapy compared with no-radiotherapy (all p > 0.05). Among patients with N1 stage, the radiotherapy group exhibited a median overall survival (mOS) of 21 months (95% CI, 19.82 to 22.18), while the non-radiotherapy group showed a slightly lower mOS of 18 months (95% CI, 16.88 to 19.12). Similarly, in terms of median cancer-specific survival (mCSS), the radiotherapy group demonstrated a mCSS of 22 months (95% CI, 20.79 to 23.21), whereas the non-radiotherapy group had a slightly shorter mCSS of 19 months (95% CI, 17.81 to 20.19). Radiotherapy reduced the all-cause mortality rate and cancer-specific mortality rate among patients with the N1 stage and T4 stage (all p < 0.05). In contrast, the patients in the radiotherapy group with the N0 stage (mOS, 28 months versus 34 months; mCSS, 30 months versus 41months), or primary focus on the body and tail of the pancreas (mOS, 23 months versus 29 months; mCSS, 25 months versus 32 months), or T1 stage (mOS, 36 months versus 113 months; mCSS, 36 months versus 104 months) exhibited a higher all-cause mortality rate and cancer-specific mortality rate compared to those without radiotherapy (all p < 0.05). Subgroup analysis indicated N1 stage pancreatic cancer patients with T2-4 stage, primary focus on the head of the pancreas, young age of onset, and combination chemotherapy were in favor of the adjuvant radiotherapy group (all p < 0.05). Our analysis demonstrates that adjuvant radiotherapy may be beneficial for N1 stage (N+) pancreatic cancer patients who have undergone up-front radical surgery with T2-4 stage, primary focus on the head of the pancreas, young age of onset, and receiving combination chemotherapy. However, radiotherapy needs to be used with caution in patients with T1 stage, N0 stage (N-), or primary focus on the body and tail of the pancreas. These findings may contribute to the development of personalized selection criteria for adjuvant radiotherapy in post-surgical pancreatic cancer patients.

Gut Microbiome and Metabolite Characteristics Associated With Different Clinical Stages in Non-Small Cell Lung Cancer Patients.

Our research has pinpointed the gut microbiome's role in the progression of various pathological types of non-small cell lung cancer (NSCLC). Nonetheless, the characteristics of the gut microbiome and its metabolites across different clinical stages of NSCLC are yet to be fully understood. The current study seeks to explore the distinctive gut flora and metabolite profiles of NSCLC patients across varying TNM stages. The research team gathered stool samples from 52 patients diagnosed with non-small cell lung cancer (NSCLC) and 29healthy individuals. Subsequently, they performed 16S rRNA gene amplification sequencing and untargeted gas/liquid chromatography-mass spectrometry metabolomics analysis. The study revealed that the alpha-diversity of the gut microbiome in NSCLC patients at different stages did not exhibit statistically significant differences. Notably, Lachnospira and Blautia were more abundant in healthy controls. The distribution of gut microbial species in patients with varying stages of NSCLC was uneven, with Bacteroides and Bacteroidaceae being most prevalent in stage T2, and Prevotella dominating in stage T4. Levels of Ruminococcus gnavus were notably elevated in stages N3 and M. The genus levels of Klebsiella, Parabacteroides, and Tannerellaceae were higher in stage II patients. Rodentibacter was the bacterium with increased levels in stage III NSCLC patients. Further metabolomics studies revealed significantly elevated levels of quinic acid and 3-hydroxybenzoic acid in the healthy control group. In contrast, Stage I+II non-small cell lung cancer (NSCLC) patients exhibited reduced levels of L-cystathionine. Notably, quinic acid, phthalic acid, and L-lactic acid were observed to be increased in Stage III+IV NSCLC patients. Compared to the analysis of a single microbial dataset, this study provides deeper functional insights by incorporating comprehensive metabolomic profiling. This approach demonstrates that both the gut microbiome and associated metabolites are altered in NSCLC patients across different clinical stages. Our findings may offer novel perspectives on the pathogenesis of NSCLC at various TNM stages. Further research is warranted to validate and clinically apply these potential biomarkers.

Lymph Node Metastasis for pN+ Superficial Esophageal Squamous Cell Carcinoma.

This study aimed to analyze lymph node metastasis (LNM) distribution in superficial esophageal squamous cell carcinoma (ESCC) and its impact factors on survival. We reviewed 241 pT1N+ ESCC cases between February 2012 and April 2022 from 10 Chinese hospitals with a high volume of esophageal cancer (EC). We analyzed clinicopathological data to identify overall survival (OS) risk factors and LNM distribution in relation to tumor invasion depth. Of the 241 patients, 26 (10.8%) had pT1a cancer and 215 (89.2%) had pT1b cancer. We showed that N3 stage, ≤ 28 lymphadenectomies, and nerve infiltration (NI) were negative factors for OS in superficial pN+ ESCC, whereas the OS was not definitively affected by the tumor depth and the choice of adjuvant therapy. In general, the LNM rates of the 193 pT1N+ ESCC cases can be ranked in the following order: station 106recR > station 106recL > station 1 > station 7 > station 2. With deeper tumor invasion, the higher LNM rate was observed near the bilateral recurrent laryngeal nerves (RLN), but there was no statistically significant difference. In superficial ESCC, LNM was frequently observed along the 106recR (35.8%) and 106recL (25.6%) stations. Advanced N-staging (N3) was a major negative impact factor in prognosis, and adequate lymph nodes dissected (LND) (N > 28) improved OS of pT1N+ ESCC. However, in superficial ESCC, tumor infiltration depth did not affect patients' OS or the distribution of positive LNs. The optimal adjuvant treatment that favors survival for these patients required further investigation.

The association between level IV/V metastasis and the recurrence, distant metastasis, and survival outcomes in hypopharyngeal squamous cell carcinoma.

The presence of level IV/V metastasis is a significant prognostic factor for patients with oral and oropharyngeal cancer, while level IV lymphadenopathy defines the N3 stage in nasopharyngeal carcinoma. However, the current staging system for hypopharyngeal squamous cell carcinoma (HPSCC) does not consider the location of involved nodes. To evaluate the risk factors and prognostic impact of level IV/V metastasis in patients with HPSCC. The analysis included 2740 HPSCC patients from the SEER (Surveillance, Epidemiology, and End Results) database, followed by a validated study on 232 patients with pathologically positive nodes (pN+) at our center. Of the 2740 patients, 1961 presented with metastatic lymph nodes (LNs), 20.8% and 14.1% had nodal involvement in level IV and level V, respectively. Multivariate analysis revealed that N3 and M1 stages were independently associated with level IV/V metastasis. Level IV metastasis was the sole independent adverse factor for overall survival (OS) among all LN regions (p < 0.05). Regarding cancer-specific survival (CSS), only level IV and V involvement were independent predictors of prognosis (p < 0.05). The rate of pN+ at levels IV and V in our center was 35.8% and 16.4%, respectively. The advanced pN stage was independently associated with metastasis to level IV or V. Patients with level IV/V metastasis had significantly higher rates of regional recurrence and distant metastases (p < 0.001). Multivariate analysis confirmed a significant association regarding OS, CSS, locoregional relapse-free survival (LRFS), or distant metastasis-free survival between patients with and without level IV metastasis (p < 0.05). Patients with level IV/V disease exhibited decreased survival rates across stages pN1 to pN3. Postoperative chemoradiotherapy improved LRFS in patients with level IV lymphadenopathy and OS/CSS in patients with level V metastasis. Metastasis to level IV/V was associated with a worse prognosis in HPSCC patients. The level IV/V should be considered for future improvements to the staging system. A retrospective study.

Impact of surgical intervention on overall survival in malignant pleural mesothelioma: A population-based cohort study with propensity score matching

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes. MethodsData from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases. ResultsThe study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9% and 11.2%, respectively, while for no-surgery patients, they were 34.9% and 3.7% (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95% CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades. ConclusionSurgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential.

STRATEGY OPTIMIZATION AND MODIFIED PLEURODESIS IN TREATMENT OF PATIENTS WITH RESISTANT PLEURAL EFFUSION

Pleural effusion critically reduces the quality of life. To prevent life-threatening complications, pleural puncture is performed. In case of pleural effusion resistant to drainage, the pleural cavity is usually obliterated. Research aimed at improving pleurodesis management remains relevant. Objective: The aim of the study is to improve treatment outcomes in patients with resistant pleural effusion by optimizing the timing of surgery and using a new method of pleurodesis induction. Materials and Methods: At the first stage, 68 patients with resistant pleural effusion and 61 patients with effective pleural drainage were compared. At the second stage, patients with resistant pleural effusion underwent pleurodesis: Group 1 (n=33) – on the 7th day according to S.A. Plaksin and L.I. Farshatova method, Group 2 (n=35) – according to a proprietary know-how method. The authors used Fisher's exact two-tailed test and Student's t-test for unrelated samples. Results. In patients with resistant pleural effusion, the primary tumor is predominantly localized in the mammary gland with lymph node involvement, stage N1 or higher, and metastases, stage M1 or higher. At the second stage of the study, it was found that in the second subgroup of the first group of patients, the painfulness of the procedure was significantly reduced; the drainage duration was reduced by 2.6 times; the length of hospital stay was reduced by 2.2 days; a significant decrease in the level of total protein was excluded, and quality of life indicators improved 1 month after pleurodesis. Conclusion. Reducing the time of decision-making on pleurodesis, based on the study of risk factors for the development of resistant pleural effusion, and the use of a know-how technique can significantly improve the treatment results and the course of the immediate postoperative period.

Does T1c–2N0–1M0 triple negative breast cancer derive a benefit from neoadjuvant chemotherapy?

ObjectivesAlthough neoadjuvant chemotherapy (NCT) is a standard approach for operable triple negative breast cancer (TNBC), the potential risks brought by it should also be noticed. Is the expanding indication of NCT to T1cN0M0 population appropriate? We conducted an investigation to compare the long-term survival of small tumor TNBC between NCT and adjuvant chemotherapy (ACT).MethodsFor this propensity-matched analysis, we used data from Surveillance, Epidemiology, and End Results (SEER) database. We enrolled 1183 cases with NCT and 2550 cases with ACT who are AJCC clinical T1c–T2 N0–N1, diagnosed with invasive triple-negative breast cancer, from 2016 to 2017. The propensity score matching was utilized to minimize baseline characteristics bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression model.ResultsCompared with patients receiving ACT, patients with NCT in this study presented a higher proportion of younger age, T2 stage, N1 stage, and underwent more mastectomy. Multivariate analysis in matched patients showed that NCT had no significant survival benefit compared with ACT in T1c–2N0–1M0 TNBC patients. Stratified analyses by T stage and N stage demonstrated NCT mainly presented a survival advantage in patients with N1 stage. Further investigation found that NCT didn’t improve BCSS (HR, 0.472; 95% CI 0.135–1.647; P = 0.239) and OS (HR, 0.392; 95% CI 0.147–1.047; P = 0.062) for patients with T1cN0M0 TNBC; however, it was associated with improved OS (HR, 1.951; 95% CI 1.003–3.797; P = 0.049) only for patients with T2N1M0 TNBC.ConclusionsIn this study, we did not find any profit brought by NCT in the stage I and stage IIa cohorts, but even more unfavorable outcomes appeared in the T1cN0M0 cohort. Therefore, whether the candidates of NCT should be extended to T1cN0M0 still need to be cautious.

Prognostic value of immuno-inflammatory biomarkers in esophageal squamous cell carcinoma patients receiving immunotherapy combined with chemoradiotherapy and its association with immuno-genomic landscape

BackgroundThe clinical significance of immuno-inflammatory indicators and the underlying biological basis in patients with esophageal squamous cell carcinoma (ESCC) who receive chemoradiotherapy (CRT) combined with immunotherapy remains unclear. This study aims to evaluate the prognostic value of immuno-inflammatory biomarkers, develop a prognostic model, and explore the underlying mechanisms.MethodsThis study included 212 ESCC patients who received CRT and anti-PD-1 immunotherapy. Association between progression-free survival (PFS) and immuno-inflammatory biomarkers, including absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio was analyzed. A nomogram was built based on the independent prognostic factors identified using multivariable Cox regression model. Pre-treatment tumor samples from 47 patients were collected for RNA sequencing to investigate the immune-related tumor microenvironment.ResultsPatients experienced significant changes in immuno-inflammatory biomarkers during CRT, which gradually recovered after radiotherapy. Body mass index < 18.5 (HR, 1.85; P = 0.032), N3 stage (HR, 2.41; P = 0.002), high pre-CRT PLR (HR, 1.53; P = 0.037), low ALC nadir (HR, 1.84; P = 0.006), and high post-CRT NLR (HR, 2.12; P = 0.002) were independent prognostic factors for unfavorable PFS, which were incorporated into a nomogram with a concordance index of 0.70 (95% CI, 0.67–0.72). High-risk patients stratified by the nomogram had worse survival and were associated with lower levels of leukocyte and T cell activation, proliferation, and migration and less intratumoral immune cell infiltration.ConclusionsPre-CRT PLR, ALC nadir during CRT, and post-CRT NLR were significantly associated with PFS in patients with ESCC receiving CRT and immunotherapy. A nomogram model with good prognostic ability was developed.

Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial.

The antidepressant efficacy and safety of seltorexant monotherapy in major depressive disorder (MDD) was investigated in a placebo-controlled, placebo lead-in, randomized, double-blind, phase 1b study. Participants were randomized to receive seltorexant (20 mg or 40 mg) or placebo. The treatment effect was assessed by changes in the Hamilton Rating Scale for Depression-17 item (HDRS17) from treatment-period baseline to week 5 in lead-in placebo non-responders ("enriched" intent-to-treat analysis set). As a secondary outcome, the effect of seltorexant on HDRS17 was assessed in patients with and without subjective insomnia. Seltorexant's effects on polysomnography, serum cortisol, and cortisol waking response were also measured. In total, 128 participants were enrolled, including 86 in the enriched sample (lead-in placebo non-responders). The mean changes from baseline (SD) in HDRS17 score at week 5 differed significantly across arms: -7.0 (5.04) for seltorexant 20 mg, -5.5 (4.34) for seltorexant 40 mg, and -4.4 (3.67) for placebo (p = 0.0456), which was attributable to the difference between the 20 mg and placebo arms (p = 0.0049). Improvement in depression severity at week 5 for seltorexant 20 mg was greater in patients with higher baseline insomnia severity (nominal p = 0.0059). The treatment benefit in the 20 mg arm remained significant when HDRS scores were adjusted by removing the sleep items (nominal p = 0.0289). The mean HDRS17 change versus placebo was numerically larger in the 20 mg than the 40 mg arm, consistent with data from a previous study in which seltorexant was administered adjunctively to conventional antidepressants. In secondary analyses, the waking cortisol response decreased in the 20 mg arm but not the 40 mg or placebo arms, and while total sleep increased more in the 40 mg arm, this arm also showed reduced REM onset latency and increased stage N1 sleep, which were not evident in the 20 mg arm. These biomarker data suggest mechanistic hypotheses that may account for the apparent curvilinear dose-response relationship of seltorexant. Trial Registration: ClinicalTrials.gov, NCT03374475.

Model-Based Electroencephalogram Instantaneous Frequency Tracking: Application in Automated Sleep-Wake Stage Classification.

Understanding sleep stages is crucial for diagnosing sleep disorders, developing treatments, and studying sleep's impact on overall health. With the growing availability of affordable brain monitoring devices, the volume of collected brain data has increased significantly. However, analyzing these data, particularly when using the gold standard multi-lead electroencephalogram (EEG), remains resource-intensive and time-consuming. To address this challenge, automated brain monitoring has emerged as a crucial solution for cost-effective and efficient EEG data analysis. A critical component of sleep analysis is detecting transitions between wakefulness and sleep states. These transitions offer valuable insights into sleep quality and quantity, essential for diagnosing sleep disorders, designing effective interventions, enhancing overall health and well-being, and studying sleep's effects on cognitive function, mood, and physical performance. This study presents a novel EEG feature extraction pipeline for the accurate classification of various wake and sleep stages. We propose a noise-robust model-based Kalman filtering (KF) approach to track changes in a time-varying auto-regressive model (TVAR) applied to EEG data during different wake and sleep stages. Our approach involves extracting features, including instantaneous frequency and instantaneous power from EEG, and implementing a two-step classifier for sleep staging. The first step classifies data into wake, REM, and non-REM categories, while the second step further classifies non-REM data into N1, N2, and N3 stages. Evaluation on the extended Sleep-EDF dataset (Sleep-EDFx), with 153 EEG recordings from 78 subjects, demonstrated compelling results with classifiers including Logistic Regression, Support Vector Machines, Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LGBM). The best performance was achieved with the LGBM and XGBoost classifiers, yielding an overall accuracy of over 77%, a macro-averaged F1 score of 0.69, and a Cohen's kappa of 0.68, highlighting the efficacy of the proposed method with a remarkably compact and interpretable feature set.

Sleep and Depressive Symptoms in Sedentary Community-Dwelling Older Adults With Sleep Complaints: Findings From Ambulatory Sleep EEG.

There is limited and inconsistent evidence on the association between electroencephalography (EEG) measured sleep and depressive symptoms among community-dwelling older adults. This study aimed to investigate the cross-sectional association between EEG-measured sleep and depressive symptoms. Using baseline data from a randomized clinical trial, we included 66 sedentary community-dwelling older adults with sleep complaints (≥ 1 self-reported insomnia symptom). Sleep was measured using an in-home sleep EEG (Sleep Profiler™) for 2 nights and the Geriatric Depression Scale (GDS-15) was used to measure depressive symptoms. Multiple linear regression analyses were conducted with each sleep parameter as the primary predictor and GDS score as the outcome, adjusting for age, sex, race, education, marital status, chronic conditions, and Montreal Cognitive Assessment (MoCA) score. Several sleep variables were associated with depressive symptoms (GDS score), including a higher percentage of sleep stage N1 (B = 0.11, 95% confidence interval [CI]: 0.02 - 0.20) and N2 (B = 0.04, 95% CI: 0.00 - 0.08), a lower percentage of N3 sleep (B = -0.04, 95% CI: -0.08 to -0.01), greater wake after sleep onset (B = 0.01, 95% CI: 0.00 - 0.02), and a greater number of awakenings ≥90s/hour (B = 0.87, 95% CI: 0.21-1.53). Our study reveals that among sedentary community-dwelling older adults with sleep complaints, more lighter sleep (stage N1, N2), less deep (N3) sleep, and increased awakenings are associated with more depressive symptoms. Sleep interventions aimed at enhancing sleep architecture may also help alleviate depressive symptoms in this population.