145 Background: Given that Deficient Mismatch Repair (dMMR) colon cancer patients respond poorly to conventional chemotherapy but immunotherapy significantly improves pCR rates in this population, this study aims to explore whether neoadjuvant immunotherapy can increase the rate of R0 resection with preservation of adjacent organs in dMMR T4 colon cancer patients and investigate the optimal regimen of immunotherapy. Methods: This single-arm, open-label, phase II trial was conducted at Peking Union Medical College Hospital in China. Patients were eligible for enrollment if they had immunohistochemically confirmed colon adenocarcinoma with confirmation of dMMR and clinical T 4 stage (defined as a tumor has invaded the serosal surface [cT 4a ] or has invaded or adhered to adjacent organs or structures [cT 4b ]). All patients are planned to receive three cycles of camrelizumab (200mg intravenously administered at the beginning of each cycle every 3 weeks) followed by radical surgery. Surgery was scheduled 2–4 weeks after three cycles. The primary endpoint of this study was the R0 resection rate in all patients who received surgery (defined as resection with a microscopic negative margin). Secondary endpoints included the rate of pCR (defined as no residual viable tumor in either the tumor bed or the lymph nodes), tumor regression grade (TRG), the incidence of adverse event (AE) during neoadjuvant immunotherapy. Results: A total of 18 patients with clinical T 4 stage and dMMR colon cancers were deemed eligible for enrollment and 17 patients were included in per-protocol set analysis from April 2024 to July 2025. The primary endpoint was evaluable in 17 patients, with 16 patients having R0 resection of 94.1%. Pathological response was observed in 14 of 16 patients, including 11 with pathological complete response. The pCR associated with a decreased trend density of PD-L1+ cells [139.3 (99.0, 272.6) cells/mm 2 vs 323.1 (114.3, 528.2) cells/mm 2 , P =0.157]. All patients experienced treatment-related AEs (100%) during neoadjuvant immunotherapy. Sixteen patients (94.1%) had Grade 1-2 AEs, while 1 patients had Grade 3 AE. Conclusions: Three cycles of mono-immunotherapy appear to be a regimen for patients with dMMR T 4 colon cancer with acceptable surgical efficacy and safety. Clinical trial information: NCT06215677 .
BACKGROUND:The tumor microenvironment, particularly the tumor stroma, plays a critical role in tumor progression, immune evasion, and therapeutic resistance. However, its interaction with the immune landscape in rectal cancer (RC) remains incompletely understood. This study aimed to comprehensively characterize the stromal-immune ecosystem associated with the tumor stroma ratio (TSR) in RC and to evaluate its clinical and therapeutic relevance. METHODS:We analyzed a multicenter cohort of 498 patients with treatment-naïve RC in whom TSR was assessed on H&E-stained sections. Integrative multi-omics analyses were performed, including bulk RNA sequencing (n=118) and single-cell RNA/T-cell receptor (TCR) sequencing (n=10). Key findings were validated by immunohistochemistry (n=114) and multiplex immunofluorescence (n=20). Survival analyses and statistical comparisons were conducted to evaluate clinical associations and treatment responses. RESULTS:High TSR was an independent predictor of unfavorable disease-free survival and cancer-specific survival and was associated with aggressive clinicopathological features. Single-cell analyses revealed that TSR-high tumors exhibited a profoundly immunosuppressive microenvironment, characterized by clonally expanded terminally exhausted CD8+ T cells (CD8+ Tex-CXCL13) and activated CD4+ regulatory T cells (CD4+ Treg-TNFRSF4). Two LRRC15+ cancer-associated fibroblast (CAF) subsets (mCAF-CTHRC1 and mCAF-FAP) were enriched in TSR-high tumors. Among them, mCAF-CTHRC1 was associated with increased Treg abundance and activation features, with predicted interactions with CD4+ Treg-TNFRSF4 cells through the LGALS9-CD44 signaling axis. In addition, SPP1-expressing monocytes (Mon-SPP1) and malignant epithelial cells were prominent in TSR-high tumors and showed a predicted SPP1-CD44 interaction with T-cell subsets, suggesting potential involvement in immunosuppressive stromal-immune interactions. In patients receiving neoadjuvant therapy, pretreatment TSR-low tumors showed improved pathological response and survival outcomes compared with TSR-high tumors. In the neoadjuvant chemoradiotherapy plus immunotherapy cohort, TSR-low tumors were associated with a significantly higher major pathological response rate, whereas pathological complete response showed a non-significant trend in the same direction. CONCLUSIONS:High TSR identifies a clinically aggressive subtype of RC characterized by a profoundly immunosuppressive stromal-immune ecosystem enriched for exhausted T cells, immunosuppressive CAF programs, and SPP1-associated stromal-myeloid interactions. These findings highlight LGALS9-, LRRC15-, and SPP1-related stromal-immune pathways as candidate stromal-immune therapeutic vulnerabilities that warrant further mechanistic and preclinical validation.
Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder increasingly recognized in adolescents and adults due to advances in supportive care and disease-modifying therapies. Respiratory muscle weakness and bulbar dysfunction predispose patients to sleep-disordered breathing (SDB), which frequently manifests as nocturnal hypoventilation, central or obstructive sleep apnea, and recurrent pulmonary infections. Early recognition of SDB in SMA is critical. Polysomnography remains the diagnostic gold standard for SDB, whereas overnight oximetry or transcutaneous CO₂ monitoring may serve as alternatives when medical resources are limited. Non-invasive ventilation (NIV) is the mainstay of therapy, effectively correcting hypoventilation, reducing respiratory morbidity, and improving quality of life and survival. The timing of NIV initiation should be guided by symptoms, pulmonary function and sleep study findings. Although disease-modifying therapies such as nusinersen, risdiplam, and gene replacement have transformed motor outcomes, their impact on SDB remains unclear. Thus, comprehensive respiratory evaluation and individualized ventilatory support are still essential components of multidisciplinary care. Further studies are warranted to determine the long-term respiratory benefits of emerging therapies and to establish standardized strategies for SDB management in adolescent and adult SMA patients.
The role of adjuvant chemotherapy (ACT) in patients with locally advanced rectal cancer (LARC) who achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) remains controversial, and it is unclear whether pCR represents a uniformly low-risk state with respect to long-term outcomes. We retrospectively analyzed consecutive LARC patients who achieved pCR following nCRT and radical surgery between 2017 and 2022. Survival outcomes were assessed according to postoperative ACT administration, treatment adequacy (≥ 4 cycles vs. < 4 cycles), and baseline risk features. Among 1069 patients treated with nCRT and surgery, 251 (23.5%) achieved pCR. After a median follow-up of 49 months, no statistically significant differences in overall survival (OS) or disease-free survival (DFS) were observed between patients who received ACT and those who did not. In contrast, patients who completed an adequate course of ACT (≥ 4 cycles) demonstrated improved 4-year OS and DFS compared with those receiving fewer cycles or no ACT. This association was largely confined to patients with baseline high-risk features, while no significant survival differences were observed between different ACT regimens. These findings suggest that pCR does not represent a biologically homogeneous or uniformly low-risk condition in LARC. Adequate postoperative chemotherapy may confer survival benefit in selected high-risk patients. A risk-adapted approach to ACT warrants further investigation and prospective validation.
Purpose Positive circumferential resection margin (CRM) is an important oncological quality indicator in rectal cancer surgery. This study aimed to explore factors associated with CRM positivity after transanal total mesorectal excision (taTME) using data from a multicenter registry. Methods Patients with rectal cancer who underwent primary taTME between 2017 and 2024 were identified from the Chinese TaTME Registry Collaborative. The primary outcome was pathological CRM positivity. Nine supervised machine learning algorithms were evaluated, including logistic regression, elastic net, decision tree, random forest, XGBoost, radial support vector machine, multilayer perceptron, LightGBM, and k-nearest neighbors. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and model interpretation was performed using SHapley Additive exPlanations. Results A total of 1,625 patients from 32 institutions were included, and the CRM positivity rate was 2.77%. In the validation cohort, the radial support vector machine model showed the highest apparent AUC of 0.84. SHAP analysis identified pathological N stage, threatened mesorectal fascia on preoperative MRI, and intersphincteric resection as the most influential variables. Conclusion This exploratory analysis identified clinically plausible factors associated with CRM positivity after taTME. Because the models included intraoperative and postoperative variables, they should not be interpreted as preoperative decision-support tools. Further studies using preoperative-only variables and external validation are required.
This study aimed to evaluate the diagnostic accuracy of MRI-based Node Reporting and Data System (Node-RADS) in diagnosing lymph node metastasis (LNM) and to investigate its prognostic significance in rectal cancer (RC) patients. Patients with RC who underwent radical rectal resection (including LN dissection) without any prior anti-tumour therapy between May 2019 and April 2023 were retrospectively included. Two radiologists independently scored lymph nodes using the MRI-based Node-RADS. The diagnostic performance of Node-RADS was estimated using the area under receiver operating characteristic (ROC) curves (AUC) and compared with size criteria and MRI reports conducted by experienced radiologists. Intra- and inter-observer agreement were both assessed. Disease-free survival (DFS), which served as a key postoperative prognostic indicator, was evaluated and compared between patients with low (1–3) and high (4–5) scores. Overall, 163 patients with RC were enrolled, including 53 with LNM. There were 98 men and 65 women with a mean age of 62.6 ± 10.1 years. Node-RADS showed a larger AUC (0.912) with higher sensitivity (81
BackgroundWhile comorbid insomnia and sleep apnea are frequently encountered in clinical practice, the accuracy of home sleep apnea testing in this particular scenario has long been overlooked. Our study aims to evaluate the performance of a wrist-worn device in diagnosing sleep apnea among individuals with chronic insomnia.MethodsParticipants with chronic insomnia suspected of having sleep apnea were consecutively enrolled at a sleep center. Single-night Watch-PAT 200 monitoring was conducted in parallel with attended in-lab polysomnography.ResultsRecordings from 44 participants (41% female, age 49.1 ± 12.7 years) with a wide range of sleep duration (222.9 ~ 461.4 min) and severity of sleep apnea [apnea–hypopnea index (AHI) 0.3 ~ 83.9/h] were analyzed. Using AHIPAT ≥ 15/h as the threshold, the sensitivity, specificity, and area under the receiver operating characteristic curve for identifying moderate-to-severe obstructive sleep apnea (OSA) were 77.3% (95% CI 54.2–91.3%), 100.0% (95% CI 81.5–100.0%), and 0.92 (95% CI 0.80–0.98), respectively. Diagnostic agreement defined by clinically oriented criteria was reached in 36 (82%) subjects. The Watch-PAT overestimated total sleep time and rapid eye movement sleep duration by 19.9 min (limits of agreement −48.1 ~ 87.9 min) and 37.2 min (limits of agreement −26.1 ~ 100.6 min), respectively.ConclusionAmong individuals with chronic insomnia, the wrist-worn home sleep apnea testing maintained acceptable diagnostic performance for identifying moderate-to-severe OSA. Sleep duration and staging parameters provided by the device should be interpreted with caution.
Background: Current evidence suggests that neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) alone is insufficient for magnetic resonance imaging (MRI)–suspected lateral lymph node metastasis (LLNM) in rectal cancer. However, whether upfront TME with lateral lymph node dissection (LLND) is adequate, and whether adding nCRT before planned LLND confers additional benefit, remains controversial. Methods: Between May 2021 and September 2022, a total of 342 patients from 20 Chinese centers were enrolled, of whom 293 were included in the final analysis and received either long-course nCRT plus TME with LLND or upfront TME+LLND. Groups were balanced by propensity score matching. The primary endpoint was 3-year recurrence-free survival (RFS). Findings: After matching, the nCRT group had significantly better 3-year RFS (HR 0.54; 95% CI. 0.32–0.92; P=0.023) and locoregional recurrence-free survival (HR 0.37; 95% CI, 0.19–0.74; P=0.005); distant metastasis-free survival did not differ (HR 0.74; 95% CI, 0.37–1.47; P=0.385). In patients with pretreatment positive lateral nodes (n=141), nCRT also improved RFS (HR 0.53; 95% CI, 0.28–0.99; P=0.049) and local control (HR 0.35; 95% CI, 0.15–0.77; P=0.010). Pathologic complete response in lateral nodes after nCRT was 44.7% (34/76). Overall postoperative complication rates were similar between groups (19.8% vs 16.0%; P=0.474), as were severe complications (grade III–V, 9.4% vs 8.5%; P=0.811). Interpretation: In MRI-suspected LLNM, adding nCRT to TME with LLND significantly improves RFS and local control without increasing morbidity. Upfront surgery alone is insufficient. These findings support a combined treatment paradigm and confirm the necessity of nCRT in these patients.
Abstract Introduction Obstructive sleep apnea (OSA) is associated with increased risk of stroke, coronary heart disease (CHD), resistant hypertension (RH), type 2 diabetes (T2D), depression, cancer, and road traffic accidents (RTA). We aimed to examine tirzepatide, a dual GLP-1/GIP receptor agonist, alongside lifestyle modification (LM) for its potential to improve clinical outcomes in patients with moderate-to-severe OSA and obesity. Methods A cohort-based Markov model was constructed to track clinical outcomes over a lifetime horizon in adults with moderate-to-severe OSA and obesity, with health states defined by apnea-hypopnea index categories to capture the full spectrum of OSA severity. Transition probabilities were derived from the SURMOUNT-OSA trial, assuming extrapolation beyond trial period. Simultaneously, average body mass index (BMI) was modelled across cycles to reflect weight changes over time. The model integrated baseline characteristics from East Asian patients of the SURMOUNT-OSA trial, and risks for complications sourced from general population data in China and adjusted for BMI-related risk amplification. Age- and gender-specific background mortality rates were included, along with OSA-specific mortality linked to stroke, CHD, and RTA. The direct impact of BMI on mortality was also incorporated. Results Over a lifetime simulation, the estimated clinical burden under LM alone was substantial, with the following number of non-fatal events per 1000 patients: 127 strokes, 179 cases of CHD, 161 cases of RH, 235 cases of T2D, 507 cases of depression, 71 cases of cancer, and 333 RTA. Adding tirzepatide to LM significantly reduced the clinical burden, avoiding approximately 21 strokes (-17%), 23 cases of CHD (-13%), 20 cases of RH (-12%), 80 cases of T2D (-34%), 20 cases of depression (-4%), 10 cases of cancer (-14%), and 46 RTA (-14%) per 1000 patients. Cumulative mortality was also lower with tirzepatide yielding approximately 4.8 additional months of life. Conclusion In this lifetime modelling study, tirzepatide, in addition to LM, was estimated to reduce the incidence of major clinical events and mortality in patients with moderate-to-severe OSA and obesity in China. These findings, robust across sensitivity analyses, support the clinical and public health value of tirzepatide in this high-risk population. Support (if any) Sponsored by Eli Lilly and Company.
PURPOSE:Although robotic surgery has advanced minimally invasive techniques, its ergonomic limitations pose significant musculoskeletal risks to surgeons. This study evaluated whether the Kangduo SR-01 (KD) open console system mitigates intraoperative ergonomic strain while preserving technical performance during robotic colorectal resection. METHODS:This study utilized data from a multicenter randomized controlled non-inferiority trial comparing the efficacy and safety of KD versus Da Vinci (DV) robotic systems in assisting colorectal cancer resection. The assessment framework included ergonomic strain (Borg CR-10 Scale), team coordination (Oxford NOTECHS II), and blinded video-based technical performance analysis [Objective Structured Assessment of Technical Skills (OSATS)]. RESULTS:A total of 100 patients were included in the modified intention-to-treat analysis: 50 in the KD group and 50 in the DV group. Body mass index (BMI) and resection types were comparable between groups. Postural demands were significantly higher for neck and back during DV procedures. Discomfort increased significantly more over time (up to 3 h) in the DV group for both neck [MD (95% c.i.) -0.889 (-1.077, -0.701), P < 0.001] and back [MD (95% c.i.) -0.606 (-0.847, -0.364), P < 0.001]. Notably, both systems achieved equivalent technical proficiency (OSATS total: 29.0 vs. 29.0, P = 0.259) and team coordination (NOTECHS II: 74.0 vs. 73.0, P = 0.120) with comparable short-term outcomes. CONCLUSIONS:The Kangduo SR-01 open console system significantly alleviated musculoskeletal strain, particularly in the neck and back, during robotic colorectal surgery while maintaining equivalent technical performance. These findings position open console platforms as a viable solution to ergonomic challenges in robotic surgery without compromising team dynamics or procedural efficiency.
Objective To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor(GIST).Methods Patients with rectal GIST who underwent surgery at Peking Union Medical College Hospital from January 2015 to January 2025 were included.Clinical data were retrospectively analyzed.Patients were divided into the neoadjuvant therapy group(received preoperative ima-tinib)and the control group(underwent direct surgery without preoperative imatinib).Clinical outcomes and recurrence rates were compared between the two groups.Results A total of 74 patients meeting the inclusion criteria were included,with 43 included in the neoadjuvant therapy group and 31 included in the control group.Baseline evaluation showed that the median tumor diameter was significantly larger in the neoadjuvant therapy group than that in the control group[5.0(2.9,7.1)cm vs.2.0(0.8,3.2)cm,P<0.001].After treat-ment with imatinib,the median tumor diameter in the neoadjuvant group decreased significantly from 5.0(2.9,7.1)cm to 2.3(1.0,4.0)cm(P=0.003).There were no significant differences between the two groups in positive surgical margin rate,anal sphincter preservation rate,5-year disease-free survival,hospi-tal stay,or recurrence rate.Conclusions Neoadjuvant therapy with imatinib can effectively reduce tumor vol-ume in patients with rectal GIST.However,its therapeutic benefit still needs to be further validated by prospec-tive,large-sample clinical studies with long-term follow-up.
ABSTRACT Background Identifying reliable biomarkers for immune checkpoint therapy response remains a critical challenge in immuno‐oncology. While tumor mutation burden (TMB) effectively predicts treatment outcomes, its clinical implementation is hindered by cost and complexity. This work aimed to investigate the association between genetic alterations in the serine protease inhibitor (SERPIN) gene family and the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with melanoma or non‐small cell lung cancer (NSCLC), and to evaluate the potential of these genetic alterations as a predictive biomarker compared with TMB. Methods This study analyzed mutation data and clinical information from five cohorts comprising 797 patients with melanoma and NSCLC who underwent whole‐exome sequencing before ICI treatment, supplemented by data from The Cancer Genome Atlas. We examined gene alterations across 36 protein‐coding SERPIN genes and analyzed their correlations with overall survival, clinical responses, TMB, neoantigen levels, and immune cell infiltration. Integration of data from The Cancer Genome Atlas with single‐cell transcriptomics using Scissor computational analysis was performed to characterize T‐cell populations associated with SERPIN gene alterations. Results SERPIN gene alterations were associated with a longer overall survival and improved clinical responses to ICI therapy in both melanoma and NSCLC cohorts. These alterations correlated with higher TMB, increased neoantigen levels, and a more favorable tumor immune microenvironment characterized by enhanced presence of antitumor immune cells. Single‐cell analysis indicated that SERPIN gene alterations were linked to T‐cell populations with greater antitumor activity. The predictive performance of SERPIN alterations for overall survival was comparable to that of TMB. Conclusions Genetic alterations in the SERPIN gene family are associated with improved outcomes in ICI therapy and may serve as a cost‐effective predictive biomarker, offering a potential alternative to TMB for stratifying patients likely to benefit from immunotherapy.
Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.
Background: Earlier results from a multicenter randomized trial showed that colorectal cancer resection with KangDuo surgical robot KD-SR-01 (KD) and da Vinci Xi (DV) had similar perioperative and pathological outcomes, whereas long-term oncologic outcomes remained uncertain. Methods: Three-year follow-up data were analyzed for the full 100-patient cohort of the multicenter randomized trial (KD, n = 50; DV, n = 50). The long-term endpoints were disease-free survival (DFS) and overall survival (OS). Results: Median follow-up in both groups was 37 months (interquartile range [IQR], 34–40). Kaplan–Meier-estimated 3-year DFS rates were 85.3
3631 Background: Transanal total mesorectal excision (taTME) has emerged as a widely adopted surgical approach for rectal cancer. Prior studies have reported favorable short-term outcomes, histopathological quality, and complication profiles for taTME compared with laparoscopic total mesorectal excision (laTME). However, the long-term oncologic effectiveness of taTME remains debated. In our previous work, we demonstrated that 3-year disease-free survival after taTME was noninferior to that after laTME among patients with mid-to-low rectal cancer. Building on these findings, the present study aimed to report the 5-year overall survival (OS) between taTME and laTME. Methods: We conducted a phase 3, randomized, open-label, noninferiority trial to compare the survival outcomes of taTME versus laTME in patients with rectal cancer located below the peritoneal reflection. This trial encompassed 16 hospitals across 10 provinces in China, with a total enrollment of 1,115 patients. We set the 3-year disease-free survival (DFS) and 5-year overall survival (OS) as the primary endpoints for analysis. This analysis of the 5-year overall survival was conducted following a predefined modified intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02966483. Results: As of June 2025, the overall 5-year overall survival (OS) rate was 83.60%, comprising 86.06% in the transanal TME (taTME) group and 81.24% in the laparoscopic TME (laTME) group. The overall 5-year disease-free survival (DFS) rate was 75.90%, with DFS rates of 77.65% in the taTME group and 74.18% in the laTME group. Conclusions: Based on preliminary results from a five-year follow-up, taTME is expected to achieve a five-year overall survival (OS) that is non-inferior to laTME. Our findings will support the routine use of taTME in mid-to-low rectal cancer, particularly in men, obese individuals, and those who have received neoadjuvant therapy. Clinical trial information: NCT02966483 . 5-year survival results between the laTME group and the taTME group. laTME taTME HR 5-year OS(97.5% CI) 81.24% (77.82%-84.82%) 86.06%(83.04%-89.20%) 0.73 (0.54-1.10) 5-year DFS(95% CI) 74.18%(70.45%-78.10%) 77.65%(74.15%-81.32%) 0.86(0.68-1.11)
PURPOSE:High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT). METHODS:In this multicenter, randomized, phase III trial, patients with stage II/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier: NCT03177382). RESULTS:Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8% v 66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929]; P = .016). Metastasis-free survival (MFS; 77.7% v 67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37% v 9.80%; P < .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03% v 6.19%; P = .943). Although grade ≥3 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59% v 8.56%; P < .001), severe toxicities during the entire treatment course (28.02% v 24.32%; P = .371) and major postoperative complications (3.98% v 2.94%; P = .567) were comparable. CONCLUSION:Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy‑based or nondoublet-concurrent TNT regimens.
Background The role of neoadjuvant therapy in the treatment of locally advanced colon cancer has become increasingly prominent. However, radiographic assessment rarely provided an accurate prediction of pathological complete response. This study aims to improve preoperative clinical evaluation by investigating the histopathological differences in colon cancer after neoadjuvant therapy. Method This was a prospective observational study conducted at Peking Union Medical College Hospital. Patients were eligible for inclusion if they were locally advanced colon adenocarcinoma and treated with neoadjuvant therapy. Surgical specimens after neoadjuvant therapy were carefully examined by pathologists. According to the standard sampling method, the location of the tumor bed was identified and all tissues of the tumor bed were sent for microscopic examination. Results Of 32 patients, 16 (50%) were included in dMMR group. The difference in tumor location between these two groups was statistically significant (P<0.05). The dMMR group had a better pathological response, with a pCR rate of 62.5% and 3 cases (18.75%) of near pCR (TRG grade 1). In pMMR group, only 12.5% achieved pCR and 6.25% near pCR. The difference between the two groups was statistically significant (P<0.05). There was no statistical difference in gross findings of the surgical specimen between the two groups. However, there was a significant difference in the maximum diameter of residual tumor between the two groups ( P <0.05). Histopathological examination revealed mucinous pools was predominant in 50% of dMMR tumors and fibrosis was the predominant pattern in 87.5% of pMMR tumors ( P <0.05). Conclusions For patients with dMMR after neoadjuvant immunotherapy, histologic manifestations more frequently included large mucinous pools, leading to a gross overestimation of residual tumor.
Obstructive sleep apnea (OSA) is one of the major sleep disorders, which has been demonstrated to be a high-risk factor for cardiovascular disease, hypertension, and motor vehicle accidents. Pressure sensors in a contactless manner are a promising way to monitor sleep conditions outside of the hospital. However, previous studies mainly based on limited sensors are often subjected to noise contamination and constrained by the sleeper position to pressure sensors. The acquired pressure signals are of poor quality or even lost, which are not appropriate for the downstream task of OSA event detection. To address this issue, we designed a sensitive piezoelectric ceramic sensor array (PCSA) by aligning sixteen sensors embedded into a mat covering the chest and abdomen area, which can capture the changes of weak pressure signals under a sleeping mattress with a thickness of up to 30cm. Based on PCSA, we recruited 36 adult volunteers from the Peking Union Medical College Hospital and conducted a pilot study to acquire overnight pressure signals along with polysomnography recordings. Subsequently, we developed an automated OSA event detection method named DRFNet. The main advantage of DRFNet is that it can well capture the time-domain and frequency-domain features from different views by fusing ResNet18 and DenseNet121 networks. Experiment results showed that DRFNet can achieve 75.19 % sensitivity, 87.78 % specificity, and 81.48 % accuracy, which is competitive with existing state-of-the-art methods. Combined with PCSA, it can be potentially deployed into an embedded device and provide contactless sleep monitoring service in home settings.