目的 观察中低位局部进展期直肠癌患者术前同期加量调强放疗联合希罗达化疗的临床可行性、安全性及疗效.方法 解放军总医院第一医学中心放疗科于2012年2月-2013年5月入组19例临床诊断为cT2-3N+M0直肠腺癌患者,行新辅助同期加量调强放疗(simultaneous integrated boost intensity-modulated radiation therapy,SIB-IMRT)联合希罗达同步化疗.放疗剂量分割模式:直肠原发肿瘤及盆腔转移淋巴结(pGTV)照射56.25 Gy/25次(2.25 Gy/次),高危复发区域和区域淋巴引流区(PTV)照射50 Gy/25次(2.0 Gy/次).希罗达用量为825 mg/m2,2次/d,5 d/周,共5周.放化疗结束后6～10周行全直肠系膜切除术(total mesorectal excision,TME).研究主要结局指标为病理完全缓解率、保肛率,及3年、5年、7年的总生存(overall survival,OS)、局部复发率(local recurrence rate,LRR)、远处转移率(distant metastasis rate,DMR)、无病生存(disease-free survival,DFS).次要结局指标为急性期及晚期不良反应、TN降期率、围术期并发症.结果 19例患者中位年龄为57(34～70)岁,其中女性3例,男性16例.19例均完成同步放化疗及TME手术,早、晚期不良反应均为1～2级,未见3～4级严重不良反应.病理完全缓解率21.1％(4/19),保肛率73.7％(14/19),R0切除率100％,TN降期率66.7％(20/30).围术期并发症发生率15.8％(3/19),分别为粘连性肠梗阻、结扎线脱落、直肠阴道瘘各1例.3年OS、LRR、DMR、DFS分别为94.4％(17/18)、5.1％(1/18)、0、94.4％(17/18);5年OS、LRR、DMR、DFS分别为88.2％(15/17)、10.5％(2/17)、5.3％(1/17)、88.2％(15/17);7年OS、LRR、DMR、DFS分别为82.3％(14/17)、15.8％(3/17)、10.5％(2/17)、82.3％(14/17).结论 局部进展期中低位可手术切除直肠癌行术前SIB-IMRT联合化疗,获得较满意的病理完全缓解率、保肛率及3年、5年、7年OS、LRR、DMR、DFS,未见3～4级不良反应,耐受性好,未增加围术期并发症发生率,安全可行.

The aim of this study was to evaluate the safety and clinical efficacy of a combined preoperative regimen consisting of volumetric modulated arc therapy-simultaneous integrated boost and capecitabine chemotherapy for distal rectal cancer. A total of 26 patients with locally advanced distal rectal cancer were enrolled from March 2015 to May 2016. The radiation dose fractionation was 58.75 Gy/25 fractions (2.35 Gy/fraction) for rectal tumor and pelvic lymph node metastasis and 50 Gy/25 fractions for pelvic lymph node stations, accompanied with simultaneous capecitabine chemotherapy. Completion of the simultaneous chemotherapy was ensued by 1 week of rest and then another cycle of induction chemotherapy with capecitabine. A radical rectal cancer surgery was performed 6 to 8 weeks after the simultaneous chemoradiotherapy. The primary end points were the complete pathological response rate and the postoperative sphincter preservation rate. All 26 patients completed the neoadjuvant chemoradiotherapy, among which 25 received surgical treatment. The postoperative complete pathological response rate was as high as 32% (8/25), while the sphincter preservation rate was 60% (15/25), the overall tumor/node (T/N) downstaging rate was 92% (23/25), and the R0 resection rate was 100%. During the chemoradiation, the most common adverse events were grade 1 and 2; grade 3 radiodermatitis occurred in 2 cases but no occurrence of acute adverse events occurred that were grade 4 and above. After the surgery, there was one case of ureteral injury and one case of intestinal obstruction, but no perioperative deaths occurred. In conclusion, the chemoradiation regimen of preoperative volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB58.75Gy) and a single cycle of induction chemotherapy with capecitabine for patients with distal rectal cancer is safe and feasible with a satisfactory complete pathological response rate, sphincter preservation rate, and R0 resection rate.

To evaluate the feasibility, safety and short-term efficacy of preoperative capecitabine and simultaneous integrated boost IMRT-based, followed by a cycle of neoadjuvant capecitabine in patients with locally advanced rectal cancer(LARC). Between March 2015 and July 2016, a total of 43 patients with resectable stage II or III rectal cancer received capecitabine (825 mg/m2, bid d1-5 weekly) and SIB-IMRT delivering 58.75 Gy (2.35Gy/fraction) to the gross tumor and regional metastatic lymph nodes while simultaneously delivering 50Gy (2.0 Gy/fraction) to the areas at high risk for harboring microscopic disease. One cycle of capecitabine (1250 mg/m2, bid d1-14) was given one week after the completion of neoadjuvant chemoradiation (nCRT), and TME was scheduled 6 to 8 weeks after the completion of nCRT. The primary endpoint included ypCR. Secondary endpoints included acute toxicity, tumor downstaging, surgical morbidity, R0 resection, postoperative complications, sphincter preservation rate, LR, OS, and DFS. A total of 43 patients completed chemoradiation as the protocol schedule and 40 received surgical resection. 16 (40%) patients had no residual tumor in the surgical specimen. Downstaging of the primary tumor or lymph nodes was observed in 39 (97.5%) patients. Most of the adverse reactions were grade 1/2, Grade 3 diarrhea and radiation dermatitis toxicities were evaluated in two (4.7%) and three cases (7.0%). No grade 4-5 toxicities were observed. Thirty patients underwent sphincter-saving surgery. Postoperative complications included 1 case of ureteral injury and 1 case of intestinal obstruction, no death in perioperative period. Three patients who refused surgery after chemoradiation therapy were excluded from the analysis, included one patient delayed surgery due to anal edema. The 1-year estimated overall survival and disease-free survival rates were 100 and 100% respectively, and no local relapse was found. The pattern of preoperative SIB-IMRT plus concurrent capecitabine, followed by one cycle neoadjuvant capecitabine is a safe, well-tolerated treatment, gained a good pCR for patients with locally advanced rectal cancer, and the short-term outcomes could be promising.

Objective To evaluate the feasibility and clinical efficacy of preoperative simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with neoadjuvant chemotherapy of capecitabine in patients with locally-advanced low rectal cancer.Methods Between 2015 and 2016,26 patients admitted to 301 Hospital who were diagnosed with locally-advanced low rectal cancer,which was located within 5 cm from the anal verge,were enrolled in this investigation.Dose fractionation pattern was delivered:58.75 Gy in 25 fractions (2.35 Gy/fraction) for rectal cancer and lymph node metastasis and 50 Gy in 25 fractions for the pelvic lymphatic drainage area and simultaneously combined with capecitabine chemotherapy (825 mg/m2,bid d 1-5 weekly).One cycle of capecitabine (1 250 mg/m2,twice daily,d 1-14)was given at one week after the completion of chemoradiotherapy (CRT).Total mesorectal excision (TME)was performed at 6 to 8 weeks after the completion of CRT.The primary endpoints included pathological complete response rate (ypCR) and sphincter-preserving rate.The secondary endpoints included acute toxicity,tumor downstaging rate and postoperative complications.Results Twenty-six patients successfully completed neoadjuvant CRT,25 of them underwent surgical resection and one patient failed to receive surgery due to pxrianal edema.Postoperative ypCR rate was 32％ (8/25),the sphincter-preserving rate was 60％ (15/25),the tumor downstaging rate was 92％ (23/25) and the R0 resection rate was 100％.During the period of CRT,grade 1 and 2 adverse events occurred in 24 patients,grade 3 radiation dermatitis was noted in 2 cases.No ≥ grade 4 acute adverse event was observed.Postoperative complications included ureteral injury in one case and intestinal obstruction in one patient.Conclusions Preoperative SIB-IMRT combined with neoadjuvant chemotherapy of capecitabine is a feasible and safe treatment for patients with locallyadvanced low rectal cancer,which yields expected ypCR rate,R0 resection rate and sphincter-preserving rate.Nevertheless,the long-term clinical benefits remain to be elucidated.Clinical Trial Registry Chinese Clinical Trial Registry,registration number:ChiCTR-ONC-12002387.

Objective To investigate the feasibility, safety, and short?term efficacy of preoperative capecitabine and simultaneous integrated boost intensity?modulated radiotherapy ( SIB?IMRT ) followed by one cycle of neoadjuvant capecitabine in patients with locally advanced rectal cancer ( LARC ) . Methods From March 2015 to April 2016, a total of 37 patients with LARC were enrolled in this study. They received capecitabine (825 mg/m2 orally twice daily for 5 weeks, days 1?5 weekly) and SIB?IMRT (5875 Gy in 25 fractions for rectal lesion and positive lymph nodes and 5000 Gy in 25 fractions for pelvic lymphatic drainage area) . After the concurrent chemoradiotherapy, they were allowed to rest for one week. And then they received one cycle of induction chemotherapy with capecitabine (1250 mg/m2 orally twice daily for 14 days) . And total mesorectal excision ( TME ) was scheduled at 6?8 weeks after the concurrent chemoradiotherapy. The primary endpoint was pathologic complete response ( pCR) rate, and the secondary endpoints included tumor and nodal ( TN) downstaging rate, the rate of sphincter?preserving surgery, and adverse events. Results All the 37 patients successfully received the preoperative concurrent chemoradiotherapy. Only 32 patients underwent the surgical resection, 4 patients refused surgery due to symptom relief, and 1 patient delayed surgery due to perianal edema after radiotherapy. The pCR rate was 34%(11/32);the TN downstaging rate was 91%(29/32);the R0 resection rate was 100%;24 patients ( 75%) underwent the sphincter?preserving surgery. During the period of chemoradiotherapy, most of the patients experienced grade 1/2 acute adverse events and grade 3/4 adverse events occurred in 3 patients. The postoperative complications included ureteral injury (1 patient) and intestinal obstruction (1 patient), and no death occurred in the perioperative period. Conclusions For patients with LARC, preoperative SIB?IMRT combined with one cycle of capecitabine followed by TME is safe and feasible, and has good short?term efficacy and mild acute adverse events.

Objective To investigate the dosimetric feasibility of volumetric modulated arc therapy (VMAT)with a simultaneous integrated boost(SIB-VMAT58.75 Gy)for preoperative chemoradiotherapy in patients with locally advanced rectal cancer(LARC),and to provide a basis for clinical practice.Methods Nine patients with stage Ⅱ-Ⅲ rectal cancer who underwent preoperative concurrent chemoradiotherapy were involved in the study,and two plans were performed for each patient:SIB-VMAT58.75 Gy and VMAT50.00 Gy. For the SIB-VMAT58.75 Gy plan,the prescribed dose was 58.75 Gy(2.35 Gy/fraction)for the local rectal tumor and positive lymph nodes(GTV 58.75 Gy),and 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)(PTV 50Gy).For the VMAT50.00 Gy plan,the prescribed dose was 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)without a boost. The conformity index(CI),homogeneity index (HI),and dose for target areas and organs at risk(OAR)were assessed according to the dose-volume histogram. The paired t-test or nonparametric rank test was used to compare the differences between the two plans. Results Both plans met the prescription goal for PTV dose coverage. There was no significant difference in CI for the PTV between the two plans(1.0±0.0 vs. 1.0±0.0,P>0.05).The SIB-VMAT58.75 Gy plan had a worse HI than the VMAT50.00 Gy plan(0.2± 0.2 vs. 0.1± 0.0,P<0.05).There was no significant difference in V10-V50of the small intestine,bladder,femoral heads,and pelvis between the two plans(P>0.05),but D 2 cm3of the small intestine was significantly higher in the SIB-VMAT58.75 Gy plan than in the VMAT50.00 Gy plan(P=0.038). Conclusions The SIB-VMAT58.75 Gy plan for LARC achieves required target volume dose coverage and OAR dose constraints,which is safe and feasible in terms of dosimetry,and its clinical efficacy and adverse effects need further evaluation.

Preoperative concurrent chemoradiation, total mesorectal excision and adjuvant chemotherapy have become the standard of care for patients with locally advanced rectal cancer (LARC). Several studies have reported increased pathologic complete response rates and improved locoregional control with escalating doses of preoperative radiotherapy. In this study, we assess the dosimetric feasibility and impact of intensity-modulated and image-guided radiation therapy (IMRT-IGRT) with a simultaneous integrated boost (SIB) in preoperative chemoradiation for LARC. Ten rectal cancer patients treated with preoperative chemoradiation were enrolled in this study, and IMRT56.25Gy and IMRT50Gy plans were made for each patient with a CTV-PTV50Gy margin of 5 mm and a GTV-PTV56.25Gy margin of 10 mm adapted to daily KV cone-beam computed tomography (CBCT) imaging. In the boost group (IMRT56.25Gy), the prescribed doses were 56.25 Gy to the gross tumor (PTV56.25Gy) and 50 Gy to areas at high risk of harboring microscopic disease (PTV50Gy). Doses were delivered over 25 daily fractions using a SIB technique. In the no-boost group (IMRT50Gy), the prescribed dose was 50 Gy to PTV50Gy without a boost. The goals were to give at least 95% of the prescribed doses to at least 95% of the PTVs while keeping irradiated volumes of the organs at risk dose as low as possible. Differences in dose distributions between the two sets of plans were analyzed using a paired sample t-test. All IMRT56.25Gy plans met the needs of the prescribed doses and organ at risk dose constraints. Compared to IMRT50Gy, the addition of a SIB in IMRT56.25Gy resulted in significant increases in mean dose and V40Gy to the bladder and significant increases of V30Gy and V40Gy to femoral heads ( p < 0.05 for all points). There were no significant differences in dose to small bowel or pelvic bone marrow between the two sets of plans. Preoperative IMRT-IGRT with SIB for LARC is feasible dosimetrically with respect to organ at risk dose constraints. A phase II trial to evaluate the clinical safety and efficacy of this approach is being undertaken.

Objective To observe the combination effects of radiation and nimotuzumab (h-R3)or cetuximab (C225) on human esophageal squamous carcinoma cell line TE-13.Methods TE-13 cells were divided into 6 groups,including no treatment control,h-R3,C225,irradiation,h-R3 combined with irradiation,and C225 combined with irradiation.For each group,cell proliferation was evaluated by MTS assay,cell radiosensitivity was determined by clonogenic assay and the survival curve was fitted with the multi-targets single-hit model,and cell cycle distribution and apoptosis were analyzed with flow cytometry assay.Results Compared with the irradiation group,after the combination treatment of mAbs and irradiation,the cell proliferation,the cell proliferations were obviously decreased (F=325.59,P＜0.05),SF2,Do,Dq,and N values were obviously decreased,the cell apoptosis rates were significantly increased (F =120.59,P ＜ 0.05),and the percentages of cells in G0/G1 and G2/M phases were increased.The cell apoptosis rate of the C225 combined with irradiation group was higher than that of the h-R3 combined with irradiation group (F =120.59,P ＜ 0.05).The radiosensitization enhancement ratio (SER) of C225 was 1.83,higher than that of h-R3.Conclusions Both h-R3 and C225 can significantly enhance radiation damage of TE-13 cells and C225 is more effective than h-R3.

目的 探讨直肠癌术前同期加量三维适形放疗(three-dimensional conformal radiotherapy,3DCRT)、静态调强放疗(intensity-modulated radiotherapy,IMRT)和螺旋断层放疗(helical tomotherapy,HT)的剂量学特点,为临床选择直肠癌术前放疗方法提供依据.方法 对10例Ⅱ～Ⅲ期直肠癌术前同步放化疗患者分别进行3野3DCRT、9野IMRT和HT的计划设计,统一给予肿瘤原发病灶及转移淋巴结(pGTV)处方剂量56.25 Gy(分25次),高危复发区域和区域淋巴引流区(PTV)50 Gy(分25次).利用剂量体积直方图评价靶区剂量分布以及危及器官的照射剂量.结果 3种治疗计划均能满足靶区处方剂量要求;除3DCRT计划外,IMRT计划和HT计划均能满足各危及器官剂量限制要求.靶区(包括pGTV和PTV)适形指数HT＜IMRT＜3DCRT,pGTV剂量均匀指数HT＜IMRT及3DCRT.对危及器官的保护IMRT和HT优于3DCRT,HT优于IMRT.3DCRT、IMRT和HT计划的小肠V15分别为(304.7±113.2) cc、(283.5±124.8) cc和(240.7±102.0) cc,两两差异均有统计学意义.结论 此处方剂量模式下,3DCRT计划无法满足危及器官剂量限制要求.直肠癌术前同期加量放疗中IMRT和HT计划在靶区适形度和危及器官保护方面均明显优于3DCRT计划.HT较IMRT计划进一步降低了小肠、膀胱、骨盆及股骨头的照射剂量.

Objective To compare the setup errors between single-site and two-site image guidance in treating multiple metastases using Tomotherapy.Methods A total of 1 220 sets of megavoltage CT (MVCT) images from 50 multiple metastases patients were collected.The setup errors of two anatomic sites were determined by registration of MVCT images with planning images.Bland-Altman plot analysis was used to assess the coincidence of these two methods.Pearson correlation analysis was performed to evaluate the correlation of the setup errors determined by two sets of data and to analyze the deviation values of setup errors.Results The deviation values of setup errors more than 3 mm between two sites were 34％,46％ and 28％ in lateral (x),longitudinal (y),vertical (z) directions,respectively.The deviation values of setup errors more than 5 mm were 10％,16％ and 8％,respectively.The BlandAltman plot analysis showed that the 95％ agreement limits of agreement were (9.3,-10.6),(10.5,-11.7),(7.3,-6.9) mm in x,y,z directions,respectively,which were all out of 5 mm tolerance.The Pearson coefficient of correlation along all three directions was less than 0.05,and R2 was 0.074,0.475,and 0.178 in x,y,z directions,respectively.Conclusions To determine the setup errors for patients with multiple metastases,single-site image guidance method is not consistent,and the two site image guidance method would be recommended.