The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0 / El ypT puede predecir mejor la eficacia de la quimiorradioterapia neoadyuvante que el grado de regresión tumoral en pacientes con cáncer de recto localmente avanzado diagnosticados ypT1-4N0

Purpose: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). Methods: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan–Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. Results: The median follow‐up was 35.8 months (range 2.8–71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. Conclusions: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.(AU)

Clinicopathological factors predict residual lymph node metastasis in locally advanced rectal cancer with ypT0-2 after neoadjuvant chemoradiotherapy.

PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.

Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer.

Importance: Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. Objectives: To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. Design, Setting, and Participants: This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Interventions: Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. Main Outcomes and Measures: The primary end point was pathologic complete response rate. Results: Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. Conclusions and Relevance: This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Multidimensional Applications and Challenges of Riboswitches in Biosensing and Biotherapy.

Riboswitches have received significant attention over the last two decades for their multiple functionalities and great potential for applications in various fields. This article highlights and reviews the recent advances in biosensing and biotherapy. These fields involve a wide range of applications, such as food safety detection, environmental monitoring, metabolic engineering, live cell imaging, wearable biosensors, antibacterial drug targets, and gene therapy. The discovery, origin, and optimization of riboswitches are summarized to help readers better understand their multidimensional applications. Finally, this review discusses the multidimensional challenges and development of riboswitches in order to further expand their potential for novel applications.

The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0.

PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.

Research progress of All-in-One PCR tube biosensors based on functional modification and intelligent fabrication.

PCR amplification technology is the cornerstone of molecular biology. All-in-One PCR tube, as an emerging integrated device, is booming in biosensors application. All-in-One PCR tube biosensors are integrated PCR tubes designed for signal recognition, signal amplification or signal output. They enable "one-pot" detection within functionally modified and intelligently fabricated PCR tubes, effectively overcoming the limitations of conventional PCR applications, like complex procedural steps, risk of contamination and so on. Based on this, the review article summarizes the recent advance of All-in-One PCR tube biosensors for the first time as well as systematically categorizes five approaches of functional modification, three types of intelligent fabrication and relevant property characterization techniques. More emphasis is placed on the review of five ways of functional modification, including physical modification, chemical modification, UV photografting surface treatment, plasma surface modification, and layer-by-layer assembly coating. Moreover, All-in-One PCR tube biosensors covering different recognition elements range from small molecules to protein are detailed discussed on principle of sensing, providing a deeper understanding of the design and application of All-in-One-tube biosensor. Last, the future opportunities and challenges in this fascinating field are also deliberated.

4D-MRI assisted stereotactic body radiation therapy for unresectable colorectal cancer liver metastases.

This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial-caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1-2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.

KRAS status predicted by pretreatment MRI radiomics was associated with lung metastasis in locally advanced rectal cancer patients.

BACKGROUND: Mutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis. METHODS: In this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and Kaplan‒Meier survival analysis; the results were compared by the log-rank test. RESULTS: Overall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766). CONCLUSIONS: We established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.

Mediation of work-family support and affective commitment between family supportive supervisor Behaviour and workplace deviance.

Employees' Workplace Deviant Behavior (WDB) is an organizational threat to its sustainability. This study examines the impact of the supervisors' role in improving organizational behavior because of the gap in the body of knowledge indicating the inconsistency, paucity, and uncertainties of relationships between variables when relating to their underpinning theories. The conceptualized model consists of the impact of family supportive supervisor behavior (FSSB) on workers' workplace deviant behavior (WDB) while considering Affective Commitment and Work-Family Supportive Behavior Attribution between the key variables. In terms of methodology, this quantitative study analyzed 321 valid surveys through descriptive and inferential statistics to ascertain if FSSB negatively impacts employees' WDB. As findings and novelty of this study, FSSB is found to negatively affect employees' WDB, while affective commitment mediates between FSSB and employees' WDB. Work-family supportive behavior attribution and personal life attribution of employees moderated the negative relationship between affective commitment and WDB, while work productivity attribution of employees had no significant effect as a moderator. With three (out of four) hypotheses supported by empirical evidence, this research has broadened previous studies of workers' WDB and offers organizations theoretical and practical recommendations for managing employees' WDB. More studies could be conducted in the future to address limitations in this research, examine other related theories in a new context, location, and/or culture, or select other suitable research methods.

Multifunctional rolling circle transcription-based nanomaterials for advanced drug delivery.

As the up-and-comer in the development of RNA nanotechnology, RNA nanomaterials based on functionalized rolling circle transcription (RCT) have become promising carriers for drug production and delivery. This is due to RCT technology can self-produce polyvalent tandem nucleic acid prodrugs for intervention in intracellular gene expression and protein production. RNA component strands participating in de novo assembly enable RCT-based nanomaterials to exhibit good mechanical properties, biostability, and biocompatibility as delivery carriers. The biostability makes it to suitable for thermodynamically/kinetically favorable assembly, enzyme resistance and efficient expression in vivo. Controllable RCT system combined with polymers enables customizable and adjustable size, shape, structure, and stoichiometry of RNA building materials, which provide groundwork for the delivery of advanced drugs. Here, we review the assembly strategies and the dynamic regulation of RCT-based nanomaterials, summarize its functional properties referring to the bottom-up design philosophy, and describe its advancements in tumor gene therapy, synergistic chemotherapy, and immunotherapy. Last, we elaborate on the unique and practical value of RCT-based nanomaterials, namely "self-production and self-sale", and their potential challenges in nanotechnology, material science and biomedicine.

An Effective Docking-Guided Strategy for Rational Tailoring of Fluorescent Aptamer Switches of Dimethylindole Red Analogue.

The light-up aptamer-dimethylindole red (DIR) complexes have been applied in biochemistry analysis as promising signal transduction tools. However, the unfavorable repulsions between DIR and the long-sequence aptamer switch hinder the complex's further development, and it is urgent to engineer a feasible and efficient strategy for synchronously and rationally adjusting the DIR chemical structure and the DIR aptamer performance. Herein, we communicate a versatile docking-guided rational tailoring strategy to effectively upgrade a DNA aptamer which specifically turns on the fluorescence of a synthesized amino-functionalized DIR analogue (NH2-DIR). After optimizing with three-level tailoring strategies including molecule docking-guided tailoring, coarse tailoring, and fine tailoring, the NH2-DIR aptamer switch with higher binding affinity and specificity, considerable fluorescence-activation ability, and 40% shortened length was obtained. Integrating the experimental and docking results, the binding mechanism between NH2-DIR and the tailored aptamer was deciphered via three types of interactions.

Cavity hairpin ThT-light nucleic acid switches: the construction of label- and enzyme-free sensing and imaging platforms.

Thioflavin T (ThT) is a classical fluorescent dye gaining prominence in current research regarding nucleic acid conformations (NACs). However, most NACs with the ability to excite ThT fluorescent are unique or form in demanding conditions, limiting the extensiveness and depth of ThT application in sensing and imaging. Therefore, this study proposed CGG-AAA mismatched cavity hairpin ThT-light nucleic acid switches (CHTLNAS) with excellent fluorescence excitation over 500-fold higher than spontaneous, 17∼20-fold higher than ssDNA and 2.5∼5-fold higher than complementary duplex. Based on the excellent fluorescence excitation, convenient conformation formation, good sequence programmability, and flexible allosteric ability (known as the Worm-crack pod mechanism mediated by the target), it achieved the label- and enzyme-free detection of tetracycline (TET) and berberine (BB) at the pM level within 10 min. Moreover, it was found enable to realize the sensitive tracking of intracellular carriers at the nM level of ThT entry concentration, and prolongated its cell nuclear-entry time of ThT over 8 h, overcoming the non-specific high background signal interference of ThT in the nuclear region, and expanding the diversified application of ThT in cell biology research. Therefore, CHTLNAS is a more universal, practical tool than G-quadruplex or other kinds of NACs for ThT development and utilization in sensing and imaging platforms.

Prognostic impact of sarcopenia in patients with locally advanced adenocarcinoma of the esophagogastric junction treated with neoadjuvant chemoradiotherapy.

Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy. Materials and methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors. Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770). Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.

Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer.

Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.

Portable dual-aptamer microfluidic chip biosensor for Bacillus cereus based on aptamer tailoring and dumbbell-shaped probes.

As food-borne pathogens, Bacillus cereus not only produce toxins that contaminate food and threaten human health, but also rely on spores to resist extreme environments. At present, the detection of B. cereus is still at the genome level and it is not easily distinguished from other Bacilli of the same group. Herein, we obtained the aptamers of B. cereus in different phases through Cell-SELEX technology. Then, through step-by-step tailoring and molecular docking, the two best performing aptamers were ascertained and the interaction revealed between the repeated G bases in the aptamer and the polar amino acids in the α-helix of the epiprotein. Based on these aptamers, a multifunctional dumbbell-shaped probe and an ultrasensitive microfluidic chip biosensor were designed. Tests showed that the novel sensor is able to complete detection within 1 h with a limit of detection (LOD) of 9.27 CFU/mL. Moreover, the sensor can be used in complex food environments, such as milk and rice, is able to detect both vegetative cells and spores, and it can also distinguish B. thuringiensis from the same flora. This study can provide a reference for the future development of food-borne pathogenic bacteria aptamer selecting, target interaction analysis, detection methods and equipment.

MRI-based radiomics to predict neoadjuvant chemoradiotherapy outcomes in locally advanced rectal cancer: A multicenter study.

Background and purpose: Predicting tumour response would be useful for selecting patients with locally advanced rectal cancer (LARC) for organ preservation strategies. We aimed to develop and validate a prediction model for T downstaging (ypT0-2) in LARC patients after neoadjuvant chemoradiotherapy and to identify those who may benefit from consolidation chemotherapy. Materials and methods: cT3-4 LARC patients at three tertiary medical centers from January 2012 to January 2019 were retrospectively included, while a prospective cohort was recruited from June 2021 to March 2022. Eight filter (principal component analysis, least absolute shrinkage and selection operator, partial least-squares discriminant analysis, random forest)-classifier (support vector machine, logistic regression) models were established to select radiomic features. A nomogram combining radiomics and significant clinical features was developed and validated by calibration curve and decision curve analysis. Interaction test was conducted to investigate the consolidation chemotherapy benefits. Results: A total of 634 patients were included (426 in training cohort, 174 in testing cohort and 34 in prospective cohort). A radiomic prediction model using partial least-squares discriminant analysis and a support vector machine showed the best performance (AUC: 0.832 [training]; 0.763 [testing]). A nomogram combining radiomics and clinical features showed significantly better prognostic performance (AUC: 0.842 [training]; 0.809 [testing]) than the radiomic model. The model was also tested in the prospective cohort with AUC 0.727. High-probability group (score > 81.82) may have potential benefits from ≥ 4 cycles consolidation chemotherapy (OR: 4.173, 95 % CI: 0.953-18.276, p = 0.058, pinteraction = 0.021). Conclusion: We identified and validated a model based on multicenter pre-treatment radiomics to predict ypT0-2 in cT3-4 LARC patients, which may facilitate individualised treatment decision-making for organ-preservation strategies and consolidation chemotherapy.

Retrospective cohort study for thrombocytopenia during concurrent chemoradiotherapy for rectal cancer.

Background: The aim of this article was to establish the clinical prognostic models and identify the predictive radiation dosimetric parameters for thrombocytopenia during concurrent chemoradiotherapy for rectal cancer. Methods: In this retrospective cohort study, patients with rectal adenocarcinoma undergoing concurrent long-term chemoradiotherapy were included. The primary outcome of interest was grade 2 or higher (2+) thrombocytopenia (platelet(PLT) count <75,000/µL). Secondary outcomes included: grade 1 or higher thrombocytopenia (PLT count<100,000/µL) and the PLT count during chemoradiotherapy and its nadir. The risk prediction model was developed by logistic regression to identify clinical predictors of 2+ thrombocytopenia. Univariate linear regression models were used to test correlations between radiation dosimetric parameters and the absolute PLT count at nadirs. Results: This retrospective cohort comprised 238 patients. Fifty-four (22.6%) patients developed thrombocytopenia during concurrent chemoradiotherapy, while 15 (6.3%) patients developed 2+ thrombocytopenia. Four independently associated risk factors, including age, Alb level, PLT count, and chemotherapy regimen, were included in the final model and used to form a 2+ thrombocytopenia probability estimation nomogram. The C-index was 0.87 (95% CI: 0.78-0.96). The calibration plot showed a moderate agreement, and the Brier score was 0.047 (95% CI: 0.025-0.070). The total absolute volume of bone marrow irradiated by 5 Gy, 10 Gy and 15 Gy of radiation (BM-V5ab, BM-V10ab, BM-V15ab), calculated by the volume of bone marrow multiplied by the corresponding Vx, were identified as new predictors. The nadir of PLT was found to be negatively correlated with BM-V5ab (ß = -0.062, P =0.030), BM-V10ab (ß = -0.065, P =0.030) and BM-V15ab (ß = -0.064, P =0.042). Conclusion: The occurrence of 2+ thrombocytopenia during concurrent chemoradiotherapy for rectal cancer can be predicted by the patient's baseline status and chemoradiotherapy regimen, and low dose irradiation of bone marrow can affect the level of platelets during the treatment.

Dentate line invasion as a predictive factor of poor distant relapse-free survival in locally advanced lower rectal cancer with anal sphincter involvement.

BACKGROUND: While an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery. METHODS: We analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched. RESULTS: Before matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P < 0.001), disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P < 0.001) and after matching (48.0% vs. 20.0%, P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000). CONCLUSIONS: DLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.

Consolidation chemotherapy with capecitabine after neoadjuvant chemoradiotherapy in high-risk patients with locally advanced rectal cancer: Propensity score study.

BACKGROUND: The effects of consolidation chemotherapy (CC) in neoadjuvant therapy in locally advanced rectal cancer (LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy (NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear. AIM: To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval. METHODS: We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm (cT3c-cT3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC (capecitabine 1000 mg/m2 twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching (PSM) and inverse probability of treatment weight (IPTW) were used to balance the differences between the two groups. The main outcome was the complete response (CR) rate. RESULTS: A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d (range, 37-168). The CR rate was 24.3% and 16.3% (P = 0.107) in the CC and non-CC groups' original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group (27.6% vs 16.2%, P = 0.045; 25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo (range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples (73.2% vs 71.9%, P = 0.913; 92.3% vs 86.7%, P = 0.294), PSM (73.2% vs 73.5%, P = 0.865; 92.5% vs 89.3%, P = 0.612), and IPTW (73.8% vs 72.1%, P = 0.913; 92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups (49.3% vs 53.5%, P = 0.492). CONCLUSION: One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in high-risk LARC but failed to improve the long-term outcomes.

Improving the accuracy and consistency of clinical target volume delineation for rectal cancer by an education program.

BACKGROUND: Accurate target volume delineation is the premise for the implementation of precise radiotherapy. Inadequate target volume delineation may diminish tumor control or increase toxicity. Although several clinical target volume (CTV) delineation guidelines for rectal cancer have been published in recent years, significant interobserver variation (IOV) in CTV delineation still exists among radiation oncologists. However, proper education may serve as a bridge that connects complex guidelines with clinical practice. AIM: To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer. METHODS: The study consisted of a baseline target volume delineation, a 150-min education intervention, and a follow-up evaluation. A 42-year-old man diagnosed with stage IIIC (T3N2bM0) rectal adenocarcinoma was selected for target volume delineation. CTVs obtained before and after the program were compared. Dice similarity coefficient (DSC), inclusiveness index (IncI), conformal index (CI), and relative volume difference [ΔV (%)] were analyzed to quantitatively evaluate the disparities between the participants' delineation and the standard CTV. Maximum volume ratio (MVR) and coefficient of variation (CV) were calculated to assess the IOV. Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume, external iliac area, groin area, and ischiorectal fossa. RESULTS: Of the 18 radiation oncologists from 10 provinces in China, 13 completed two sets of CTVs. In quantitative analysis, the average CTV volume decreased from 809.82 cm3 to 705.21 cm3 (P = 0.001) after the education program. Regarding the indices for geometric comparison, the mean DSC, IncI, and CI increased significantly, while ΔV (%) decreased remarkably, indicating improved agreement between participants' delineation and the standard CTV. Moreover, an 11.80% reduction in MVR and 18.19% reduction in CV were noted, demonstrating a smaller IOV in delineation after the education program. Regarding qualitative analysis, the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa; 61.54% (8/13) and 53.85% (7/13) of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa, respectively. However, the education program reduced these variations. CONCLUSION: Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in mainland China. A well-structured education program could improve delineation accuracy and reduce IOVs.