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.

Patterns of failure and implications for clinical target volume definition of locally advanced T4b rectal cancer identified with magnetic resonance imaging and treated using neoadjuvant chemoradiotherapy and surgery.

BACKGROUND AND PURPOSE: Elective irradiation of the external iliac lymph nodes (EIN) has always been advocated for T4b rectal cancer with anterior organ invasion without convincing evidence. This study aimed to explore the patterns of treatment failure for locally advanced T4b rectal cancer treated using neoadjuvant chemoradiotherapy (NCRT) and surgery. This information may help to clarify whether the current definition of the clinical target volume (CTV) is still appropriate. MATERIALS AND METHODS: We retrospectively analyzed data from 126 patients with locally advanced T4b rectal cancer who received NCRT, without elective EIN irradiation, followed by surgery between January 2010 and October 2018. Pretreatment magnetic resonance imaging was used to identify the T4b disease in all cases. The locoregional recurrence (LRR) rate and EIN failure rate were evaluated, and the LRR locations were identified using a three-dimensional model. RESULTS: After a median follow-up of 53.9 months, LRR occurred in 11.1% of patients (14/126). All LRRs were located in the previously irradiated fields and below the S2-S3 junction. The EIN failure rate was 0.8% (1/126) among all patients and 1.8% (1/56) in the group with anterior genitourinary organ invasion. The estimated 4-year distant relapse-free survival, disease-free survival and overall survival were 79.3%, 73.2% and 86.9%, respectively. CONCLUSIONS: It may be feasible to exclude the external iliac region from the CTV during NCRT for locally advanced T4b rectal cancer. However, further studies are needed to clarify whether the cranial border of the CTV can be lowered.

Prognostic nomograms for predicting overall survival and cause-specific survival of signet ring cell carcinoma in colorectal cancer patients.

BACKGROUND: Signet ring cell carcinoma (SRCC) is an uncommon subtype in colorectal cancer (CRC), with a short survival time. Therefore, it is imperative to establish a useful prognostic model. As a simple visual predictive tool, nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years. Until now, there has been no nomogram to predict the outcome of CRC patients with SRCC. AIM: To build effective nomograms for predicting overall survival (OS) and cause-specific survival (CSS) of CRC patients with SRCC. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms. Performance of the nomograms was assessed by concordance index, calibration curves, and receiver operating characteristic (ROC) curves. ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis (TNM) staging system. Patients were classified as high-risk, moderate-risk, and low-risk groups using the novel nomograms. Kaplan-Meier curves were plotted to compare survival differences. RESULTS: In total, 1230 patients were included. The concordance index of the nomograms for OS and CSS were 0.737 (95% confidence interval: 0.728-0.747) and 0.758 (95% confidence interval: 0.738-0.778), respectively. The calibration curves and ROC curves demonstrated good predictive accuracy. The 1-, 3-, and 5-year area under the curve values of the nomogram for predicting OS were 0.796, 0.825 and 0.819, in comparison to 0.743, 0.798, and 0.803 for the TNM staging system. In addition, the 1-, 3-, and 5-year area under the curve values of the nomogram for predicting CSS were 0.805, 0.847 and 0.863, in comparison to 0.740, 0.794, and 0.800 for the TNM staging system. Based on the novel nomograms, stratified analysis showed that the 5-year probability of survival in the high-risk, moderate-risk, and low-risk groups was 6.8%, 37.7%, and 67.0% for OS (P < 0.001), as well as 9.6%, 38.5%, and 67.6% for CSS (P < 0.001), respectively. CONCLUSION: Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC, which are superior to the conventional TNM staging system.

Preliminary results of simultaneous integrated boost intensity-modulated radiation therapy based neoadjuvant chemoradiotherapy on locally advanced rectal cancer with clinically suspected positive lateral pelvic lymph nodes.

BACKGROUND: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs. METHODS: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated. RESULTS: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence. CONCLUSIONS: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).

Evaluation of the gestational diabetes mellitus diagnostic criteria recommended by the international association of diabetes and pregnancy study group for long-term maternal postpartum outcomes in mainland China.

The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, ß cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, ß cell function (homeostasis model assessment ß-cell function index (HOMA-ß) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum ß-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.