Association between the nutritional status and radiation pharyngeal mucositis in patients with head and neck cancer during radiotherapy:A longitudinal study

Objective Radiation mucositis,especially pharyngeal mucositis,severely affects the oral intake of patients of head and neck cancer(HNC)during radiotherapy.Whether the nutritional status affects the severity of pharyngeal mucositis is currently unknown.This study investigated the incidence of malnutrition and radiation pharyngeal mucositis in patients with HNC during radiotherapy and analyzed the impact of the nutritional status on radiation pharyngeal mucositis.Methods Consecutive patients with HNC receiving radiotherapy were recruited for this longitudinal observational study.Data were collected at baseline(T_(1)),midtreatment(T_(2)),and at the end of treatment(T3).The Common Terminology Criteria for Adverse Events version 4.0 and the Global Leadership Initiative on Malnutrition criteria were used to assess pharyngeal mucositis and the nutritional status,respectively.Results There were 348 HNC patients who completed all assessments.The pharyngeal mucositis of patients with HNC was aggravated during radiotherapy(χ^(2)=553.521,P<0.001).At T3,56.0%of patients had moderate or severe pharyngeal mucositis.The proportion of patients with malnutrition increased significantly during treatment(21.3%at T_(1)vs 46.8%at T_(2)vs 76.1%at T3,χ^(2)=209.768,P<0.001).Both a multivariable analysis of generalized estimating equations and a logistic regression analysis showed that pharyngeal mucositis was associated with malnutrition.Conclusions Malnutrition was common in patients with HNC during radiotherapy,and it was closely related to pharyngeal mucositis.Joint interventions targeting nutrition and symptom management should be considered for patients with HNC.

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: Clinical features, management, and outcome of 37 patients

AIM： To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin＇s lymphoma （PICL）. METHODS： A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS： Twenty-five patients presented with Ann Arbor stage Ⅰ PICL and 12 with Ann Arbor stage Ⅱ PICL. Thirty-five patients underwent surgery （including 31 with complete resection）, 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival （OS） rates were 51.9% and 44.5%. The corresponding diseasefree survival （DIS） rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment （P= 0.001）. While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS （P = 0.031） for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemotherapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy.CONCLUSION： Combined surgery and chemotherapy is recommended for treatment of patients with PICL, Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

Phase Ⅰ study of postoperative radiotherapy combined with capecitabine for gastric cancer

AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer.

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,whileΔV(%)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 China's Mainland.A well-structured education program could improve delineation accuracy and reduce IOVs.

Efficacy and toxicity of capecitabine combined with intensitymodulated radiotherapy after D1/D2 lymph node dissection in patients with gastric cancer

BACKGROUND Adjuvant chemoradiotherapy(ACRT)with oral capecitabine and intensitymodulated radiotherapy(IMRT)were well tolerated in a phase I study in patients who had undergone partial or total gastrectomy for locally advanced gastric cancer(GC).This phase II study aimed to further determine the efficacy and toxicity of this combination after radical resection and D1/D2 lymph node dissection(LND)for patients with locally advanced GC.AIM To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced GC.METHODS Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this study.The patients received ACRT comprising IMRT(total irradiation dose:45 Gy delivered in daily 1.8-Gy fractions on 5 d a week over 5 wk)and capecitabine chemotherapy(dose:800 mg/m²twice daily throughout the duration of radiotherapy).The primary study endpoint was disease-free survival(DFS),and the secondary endpoints were overall survival(OS),toxic effects,and treatment compliance.RESULTS The 3-year DFS and OS were 66.2%and 75%,respectively.The median time to recurrence was 19.5 mo(range,6.1-68 mo).Peritoneal implantation(n=10)was the most common recurrence pattern,and the lung was the most common site of extra-abdominal metastases(n=5).Nine patients developed grade 3 or 4 toxicities during ACRT.Two patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of capecitabine.There were no treatmentrelated deaths.CONCLUSION The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.

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(c T3c-c T3d), 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/m^(2) 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 highrisk LARC but failed to improve the long-term outcomes.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer:a single-center,single-arm,prospective Phase II trial(PKUCH-R02)

Background:Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk,locally advanced rectal cancer.However,the benefit of more intensive total neoadjuvant treatment(TNT)is unknown.This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer.Methods:This was a single-center,single-arm,prospective Phase II trial in Peking University Cancer Hospital(Beijing,China).Patients received three cycles of induction oxaliplatin and capecitabine(CapeOX)followed by chemoradiotherapy and two cycles of consolidation CapeOX.The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate,completion of TNT,and pathological downstaging rate.Results:Between August 2017 and August 2018,68 rectal cancer patients with at least one high risk factor(cT3c/3d/T4a/T4b,cN2,mesorectal fascia involvement,or extramural venous invasion involvement)were enrolled.The overall compliance of receiving the entire treatment was 88.2%(60/68).All 68 patients received induction chemotherapy,65 received chemoradiotherapy,and 61 received consolidation chemotherapy.The Grade 3–4 adverse event rate was 30.8%(21/68).Nine patients achieved clinical complete response and then watch and wait.Five patients(7.4%)developed distant metastasis during TNT and received palliative chemotherapy.Fifty patients underwent surgical resection.The complete response rate was 27.9%.After a median follow-up of 49.2 months,the overall 3-year disease-free survival rate was 69.7%.Conclusions:For patients with high-risk rectal cancer,this TNT regimen can achieve favorable survival and complete response rates but with high toxicity.However,it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

铜催化磷酰基叠氮参与的三组分聚合制备聚膦酰基脒

为进一步发展高效的多组分聚合方法,构建有应用前景的高分子材料,本文报道了一种基于一价铜催化的,以叠氮磷酸二苯酯(DPPA)、二炔和二胺为单体的多组分聚合方法,在N,N-二甲基甲酰胺(DMF)中室温反应4 h,制备了一系列聚膦酰基脒,产率高达90%,重均分子量高达54000 g/mol,仅生成氮气为副产物.DPPA参与聚合具有后修饰的潜在应用,克服传统磺酰基叠氮后修饰困难的缺点.以含缩硫酮的二胺为聚合单体可制备具有特殊结构、活性氧敏感的聚膦酰基脒,在活性氧刺激下实现聚合物的降解.通过核磁共振波谱,凝胶色谱及基质辅助激光解吸飞行时间质谱确定聚合物结构、分子量及重复单元,并研究了炔类单体的刚柔性和胺类单体的位阻效应对聚合反应的影响.该聚合方法为多组分聚合提供了一种新的途径,拓宽了高分子材料的应用范围,为下阶段探索聚脒材料的应用奠定基础.