Patterns of failure and clinical outcomes of radiotherapy for cervical esophageal carcinoma / 中华放射医学与防护杂志

Objective To review the failure patterns and clinical outcomes for patients with cervical esophageal carcinoma (CEC) undergoing definitive radiotherapy (RT).Methods Medical records,clinical characteristics and outcomes of patients with CEC treated by definitive RT from August 2008 to May 2017 were retrospectively reviewed and analyzed.Results A total of 97 patients with squamous cell CEC were enrolled in this study with a median age of 59 years old (range 18-78 years old).There were 34 patients with limited cervical esophagus,and 63 patients with diseases beyond cervical region,respectively.There were 69,7,and 6 patients with Bronchi invasion,thyroid lobes involvement and aortic involvement,respectively.There were 11,80 and 6 patients with stage Ⅱ,Ⅲ and Ⅳ (non-regional lymph node metastases),respectively.The median dose to the gross tumor volume (GTV) was 66 Gy,in which 46 patients received above 66 Gy and 51 patients received less than 66 Gy,respectively.The median progression free survival (PFS) and overall survival (OS) were 16.03 and 23.30 months,respectively,with a median follow-up of 14.90 months.The 1,2,3-year PFS and OS were 56.86％,30.35％,26.34％,and 72.54％,47.94％,40.81％,respectively.Sixty-one patients had treatment failure at their last follow-up,in which 40,27,and 18 patients developed local failure,regional failure,and distant metastasis,respectively.Univariate analysis revealed that thyroid lobes involvement resulted in lower PFS (x2 =5.773,P＜0.05) and OS (x2 =13.461,P＜0.05),and bronchi involvement (x2 =4.283,P＜0.05) was associated with lower OS.Multivariate analysis indicated that aortic involvement and thyroid lobes involvement were associated with lower PFS (x2 =6.796,4.548,P＜0.05) and OS (x2 =13.421,10.581,P＜0.05),and GTV dose above 66 Gy was associated with higher OS (x2=5.296,P＜0.05).Conclusions Local-regional recurrence was the main failure pattern for patients with CEC after definitive RT.Aortic,thyroid lobes,and/or bronchi involvement were associated with poor prognosis,and GTV dose ≥66 Gy tended to improve OS.Prospective studies with larger population were needed to further confirm this study.

Efficacy of volumetric intensity modulated arc therapy (VMAT) combined with chemotherapy in anal squamous cell carcinoma / 中华放射医学与防护杂志

Objective To investigate the efficacy of concurrent chemoradiotherapy for anal squamous cell carcinoma (ASCC) in the era of intensity-modulated radiotherapy.Methods A total of 19 patients with ASCC who underwent definitive radiotherapy in our hospital since 2011 were collected.The survival curves were depicted with K-M method.Risk factors of disease progression were analyzed using case-control study.Results The median follow-up time was 31 months.The 3 year-LFS and 3 year-OS were 88.1％ and 91.7％,respectively.Grade 3 acute toxicities during the chemoradiotherapy were mainly white blood cell reduction (15.8％),platelet reduction (10.5％),diarrhea (15.8％),and skin reaction (31.6％).Compared with historical data,volumetric intensity modulated arc therapy was superior to conventional radiotherapy in the treatment outcome and normal tissue protection in ASCC.Univariate analysis showed that concurrent chemotherapy with capecitabine was a favorable factor in disease progression (P＜ 0.05).Conclusions Volumetric intensity modulated arc therapy for ASCC may have advantages in terms of efficacy and normal tissue protection.Concurrent chemotherapy with a double-drug regimen containing capecitabine may be a beneficial factor in disease progression.

Application value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective@#To investigate the value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy (nCRT).@*Methods@#A single-center retrospective case series study was performed. Database of mid-lower rectal cancer patients at Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute from March 2011 to June 2017 was retrieved. Inclusion criteria: (1) nCRT was completed (50.6 Gy/22 f, plus oral capecitabine); (2) radical surgery was performed within 12 weeks after nCRT treatment; (3) clinical response to nCRT was determined as clinical complete response (cCR) or near-cCR. Patients who did not undergo colonoscopy and MRI in our center during initial assessment and follow-up, or whose colonoscopy data were unable to re-evaluated, were excluded. Initial evaluation of nCRT response was carried out between 6 and 16 weeks after nCRT. The results of endoscopy (eCR, near-eCR and non-eCR) and MRI (mCR, near-mCR and non-mCR) were compared to local lesion relapse during follow-up. The consistency of the results of colonoscopy and MRI was evaluated by Kappa test (Kappa value of 0.21 to 0.40 indicates general consistency, 0.41 to 0.60 moderate consistency, and 0.61 to 0.80 high consistency). The non-regrowth disease-free survival (NR-DFS) curves of the eCR group and the near-eCR group were plotted by Kaplan-Meier method and compared by log-rank test. Clinical significance of colonoscopy examination in the following "watch and wait" strategy during follow-up period was analyzed.@*Results@#A total of 32 patients were enrolled in the study, including 21 (65.6%) males and 11 (34.4%) females with a median age of 57 years old. The differentiated type of rectal cancer included 1 (3.1%) case of well-differentiated, 26 (81.2%) of moderately differentiated and 5 (15.6%) of poorly differentiated. Clinical stage of the patients included 9 (28.1%) cases of T2-3N0 and 23 (71.9%) of T2-3N+. Median follow-up period was 48 (18 to 80) months. The local regrowth rate was 34.4% (11/32) and median interval of local regrowth was 10.0 (4 to 37) months. Initial colonoscopy evaluation was carried out at a median time of 9 (5 to 19) weeks after nCRT was completed. According to endoscopic findings, patients were divided into 3 groups, including 15 cases in eCR group, 15 cases in near-eCR group and 2 cases in non-eCR group. According to the appearance of MRI, patients were divided into 3 groups, including 8 cases in mCR group, 21 cases in near-mCR group and 3 cases in non-mCR group. The regrowth rate of eCR group was lower than that of mCR group (1/15 vs. 1/8) without significant difference (P=1.000). The regrowth rate of near-eCR group was higher than that of near-mCR group [9/15 vs. 42.9% (9/21)] without significant difference as well (P=0.500). The consistency between colonoscopy and MRI in response evaluation of cCR or near-cCR after nCRT was unsatisfactory (Kappa=0.341, P=0.011). After initial evaluation, 31 patients underwent watch and wait strategy, and 1 underwent local resection. The 1- and 3-year NR-DFS in the eCR group was both 100%, which was higher than that in the near-eCR group (53.3% and 38.9%, respectively), and the difference was statistically significant (P=0.001). During watch and wait period, 11 cases developed local regrowth by colonoscopy examination and the biopsy result included 4 case of high-grade intraepithelial neoplasia (HIN), 6 cases of adenocarcinoma and 1 case of chronic mucosal inflammation. Meanwhile lateral developmental tumor of ascending colon in 1 case and of sigmoid in a case was found by colonoscopy and confirmed as HIN by postoperative pathology. Besides, 4 cases developed colonic multiple adenoma and all underwent endoscopic resection.@*Conclusion@#Colonoscopy examination plays an important role in both initial assessment and regrowth monitoring during watch and wait strategy after nCRT treatment.

Long-term prognostic analysis on complete/near-complete clinical remission for mid-low rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

OBJECTIVE@#To investigate the long-term outcome of organ preservation with local excision or "watch and wait" strategy for mid-low rectal cancer patients evaluated as clinical complete remission (cCR) or near-cCR following neoadjuvant chemoradiotherapy (NCRT).@*METHODS@#Clinical data of 62 mid-low rectal cancer patients evaluated as cCR/near-cCR after NCRT undergoing organ preservation surgery with local excision or receiving "watch and wait" strategy at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from March 2011 to August 2017 were retrospectively analyzed. According to the approximate 1:2 pairing, 123 patients who underwent radical resection with complete pathological remission(ypCR) after neoadjuvant chemotherapy during the same period were selected for prognosis comparison. The primary endpoint of the study was 3-year non-regrowth disease-free survival (NR-DFS) and tumor specific survival (CSS). Survival analysis was performed using the Kaplan-Meier curve (Log-rank method). The secondary endpoint of the study was 3-year organ preservation and sphincter preservation.@*RESULTS@#The retrospective study included 38 male and 24 female patients. The median age was 60 (31-79) years and the median distance from tumor to anal verge was 4(1-8) cm. The ratio of cCR and near-cCR was 79.0%(49/62) and 21.0%(13/62) respectively. Local regrowth rate was 24.2%(15/62). Of 15 with tumor regrowth, 9 patients received salvage radical rectal resection and no local recurrence was found during follow-up; 4 patients received salvage local excision among whom one patient had a local recurrence occurred patient; 2 patients refused further surgery. The overall metastasis rate was 8.1%(5/62), including resectable metastasis(4.8%,3/62) and unresectable metastasis (3.2%,2/62). The valid 3-year organ preservation rate and sphincter preservation rate were 85.5%(53/62) and 95.2%(59/62) respectively. The median follow-up was 36.2(8.6-89.0) months. The 3-year NR-DFS of patients with cCR and near-cCR was 88.6% and 83.1% respectively, which was not significantly different to that of patients with ypCR (94.7%, P=0.217). The 3-year CSS of patients with cCR and near-cCR was both 100%, which was not significantly different to that of patients with ypCR(93.4%, P=0.186).@*CONCLUSIONS@#Mid-low rectal cancer patients with cCR or near-cCR after NCRT undergoing organ preservation with local excision or receiving "watch and wait" strategy have good long-term prognosis with low rates of local tumor regrowth and distant metastasis, which is similar to those with ypCR after radical surgery. This treatment mode may be used as an option for organ preservation in mid-low rectal cancer patients with good tumor remission after NCRT.

Application of MRI simulation in delineation of gross tumor volume in pre-operative radiotherapy for low rectal carcinoma / 中华放射医学与防护杂志

Objective To explore the value of MRI simulation in the pre-operative radiotherapy for locally advanced low rectal carcinoma.Methods A total of 40 patients diagnosed with locally advanced low rectal carcinoma by endoscopic biopsy and radiological staging examinations were included in this study.There were 22 male and 18 female with nedian age 58 years (range 31-80).Patients underwent CT and MRI simulation scanning in the same position and fixing device.GTV under CT images and MRI inages were delineated respectively by two experienced radiologists.Primary tumor length,tumor volume and distance of distal tumor from the anal verge were calculated by treatment planning system(TPS).The two groups of data were compared.Results The distance of distal tumor to the anal verge were all no more than 5 cm on digital examination.The mean length of GTVcT was remarkably longer than that of GTVMRI [(5.21 ±1.65) cm vs.(4.46 ± 1.51) cm,t =5.059,P ＜0.05].The mean volume of GTVcTWaS significantly larger than that of GTVMRI[(55.71 ±31.57) cm3vs.(44.02 ±25.11) cm3,t=6.977,P＜ 0.05)].The mean distance of distal tumor to the anal verge was (3.72 ± 0.93) cm,significantly longer than that of lower bounds of GTVCT to the anal verge,which had a high consistency with GTVMRI.The IMRT plan was based on CT-MRI fusion images.There were no 3-4 grade adverse effects of radiotherapy.The overall pCR rate was 32.5％.Conclusions MRI simulation could define smaller GTV and more precise lower bounds than CT.With improved accuracy of target volumes contours,the application of MRI simulation may promote the efficacy of radiotherapy and result in a reduction in the incidence of toxicities.

Clinical efficacy and safety of recombinant adenovirus-p53 combined with concurrent radiotherapy and hyperthermia in treatment of advanced soft tissue sarcoma:a study of 76 patients / 中华放射肿瘤学杂志

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53(rAdp53) injection combined with radiotherapy and hyperthermia in the treatment of unresectable advanced soft tissue sarcoma.Methods In this retrospective study, we evaluated 76 patients with unresectable advanced primary or recurrent soft tissue sarcoma treated in our hospital from November 2005 to November 2012.These patients received radiotherapy and hyperthermia with rAdp53(p53 group, n=41) or without rAdp53(control group, n=35).rAdp53((1-2)×1012viral particles each time, once a week, 8 times on average) was injected into the tumor or infused into the pelvic cavity.Radiotherapy (2 Gy each time, 5 times a week) was performed for the planning target volume at 56.3±5.3 Gy in the p53 group and 58.1±4.2 Gy in the control group, with no significant difference between the two groups (P>0.05).Superficial or deep thermotherapy was employed 8 times on average (twice a week).Clinical features, response rate, time to progression (TTP), overall survival (OS), and adverse events were compared between the two groups (P>0.05).The Kaplan-Meier method was used to calculate OS;the log-rank test was used for survival difference analysis and univariate prognostic analysis;the chi-square test was used for comparison of categorical data.Results At 2 months after treatment, the p53 group had significantly increased response rate (partial response+ complete response+ stable disease)(85% vs.54%, P=0.003) and local control rate (49% vs.23%, P=0.020) as well as prolonged TTP (12 months vs.5 months, P=0.010) and OS (48 months vs.31 months, P=0.049), as compared with the control group.No adverse events caused by radiotherapy and hyperthermia except transient fever were seen in the two groups.Conclusions Concurrent radiotherapy and hyperthermia combined with rAdp53 injection is effective and safe for patients with advanced soft tissue sarcoma.

Outcome of watch and wait strategy or organ preservation for rectal cancer following neoadjuvant chemoradiotherapy: report of 35 cases from a single cancer center / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT).</p><p><b>METHOD</b>From March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years.</p><p><b>RESULTS</b>A total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%.</p><p><b>CONCLUSIONS</b>Organ preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.</p>

Phase Ⅰ study of dose escalation of oxaliplatin added to capecitabine during intensity-modulated radiation therapy patients with locally advanced rectal cancer / 中华放射医学与防护杂志

Objective To discuss the maximum tolerated dose of oxaliplatin based on 5-fluorouracil derivative in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy.Methods From Mar 2015 to Oct 2015,15 locally advanced rectal cancer patients (T3,T4/N +) who received intensity modulated radiotherapy and concurrent chemotherapy with capecitabine and oxaliplatin were enrolled in this study.The prescription dose was 50.6 Gy for gross tumor volume(GTV) and 41.8 Gy for clinical tumor volume(CTV) in 22 fractions within 30 d with concomitant boost.There were four dose-level groups of oxaliplatin as 100,110,120 and 130 mg/m2 tri-weekly and fixed capecitabine dose (825 mg/m2 bid d1-5 per week).The first 12 patients were randomly assigned into 4 groups.For the 130 mg/m3 group,another 3 patients were enrolled because of dose-limiting toxicity (DLT).Treatment related toxicities and response rates were evaluated.Results The most common adverse events(AE) were radiation enteritis,skin reactions,nausea,fatigue,urinary system AE and bone marrow suppression.There was a trend of increase by the dose level of oxaliplatin for toxicities.Groups 100,110 and 120 mg/m2 had none DLT,while group 130 mg/m2 had 1 patient for grade 3 thrombopenia and 1 patient for grade 3 nausea.Postoperative pathology showed that all patients achieved tumor downstaging,among which 0,1,2,3 cases achieved complete remission of the four groups,respectively.Conclusions The combination regimen of capecitabine and oxaliplatin is safe and effective according to the preliminary results.The maximum tolerated dose of oxaliplatin was 130 mg/m2 tri-weekly.

Multidisciplinary treatment for a patient with locally advanced esophagogastric junc-tion cancer / 中国肿瘤临床

Since the biological characteristics of esophageal gastric junction (EGJ) cancer are different from those of gastric cancer and esophageal cancer, the choice of initial treatment is particularly important. This article introduces a case of locally advanced EGJ can-cer with single metastasis factor treated with preoperative radiochemotherapy in the Beijing Cancer Hospital. Through the multidisci-plinary team, we aim to achieve a better prognosis for this patient and propose new treatment practices for EGJ cancer.

Clinical analysis of intensity modulated radiation therapy in cervical cancer patients with para-aortic lymph node metastasis after initial treatment / 中华放射医学与防护杂志

Objective To evaluate the efficacy and toxicities of intensity modulated radiation therapy (IMRT) with or without concurrent chemotherapy in the treatment of cervical cancer patients with para-aortic lymph node (PALN) metastases after initial treatment.Methods From Oct 2008 to Aug 2013,56 cervical cancer patients with PALN metastases after initial treatment,including radical resection or pelvic radiotherapy/chemoradiotherapy,were selected for analysis.The delivered radiation dose to PALN was 55-60 Gy for GTV and 45-50 Gy for CTV respectively with 25-30 fractions during 5-6 weeks.36 patients received concurrent paclitaxel (135 mg/m2) and cisplatin (60 mg/m2) chemoradiotherapy (CRT group) and 20 patients received RT alone (RT group).Results The median follow-up time after treatment was 22.7 months (2.7 to 74.4 months).98.2％ (55/56) of patients completed RT.In CRT group,38.9％ underwent concurrent TP regimen 2-3 cycles and the rest completed one cycle.The rates of CR plus PR in CRT and RT groups were 91.7％ (33/36) and 85％ (17/20),respectively (x2 =0.516,P ＞0.05).The 3-year overall survival rate in CRT group and RT group were 57.5％ and 32.7％ (x2 =4.059,P ＜ 0.05),and 3-year progression-free survival rates were 50.4％ and 29.2％ (x2 =4.184,P ＜ 0.05),respectively.TP regimen concurrent chemoradiotherapy was more effective than radiotherapy alone.The 3-year overall survival rate was 53％ and 39.5％ in patients with isolated PALN and nonisolated PALN,respectively (x2 =4.265,P ＜ 0.05).Grade 3 or 4 acute leukopenia was found in 10 (27.8％,CRT group) and 6 (30％,RT group) patients (x2 =0.693,P ＞ 0.05).Grade 3 gastrointestinal toxicity occurred in 1 patient each group (x2 =0.847,P ＞ 0.05).Conclusions TP regimen concurrent CRT is associated with better survival than RT alone,and the treatment toxicities could be tolerant.

Analysis of dosimetry and clinical outcome using intensity modulated radiation therapy for early breast cancer patients after breast conservative surgery / 中华放射医学与防护杂志

Objective To analyze the dosimetfic benefits, clinical effect and side-respond of whole breast using intensity modulated radiotherapy for early breast cancer after conservative surgery. Methods From Oct.2004 to Aug. 2005,103 patients received the whole breast intensity modulated radiation therapy (IMRT). A dosimetric comparison of IMRT with conventional radiotherapy (CR) was performed on each patient. The cosmetic results, clinical effect and side-respond were observed. Results The average volume proportion of 95% and 107% prescribed dose was 95.8% ± 4.90% and 84.0% ± 20.7% (t = 9.60, P < 0.01) with IMRT and CR in clinical target volume, respectively. The V20 (lung volume of aceepted> 20 Gy/all lung volume × 100%) of the ipsilateral lung were 15.70% ± 4.64% and 23. 11% ± 7.88% (t = - 13.3, P < 0.01). The V30of the heart were 4.44% ±3.93% and 15.55% ± 10.89%(t = - 11.3, P< 0.01) with IMRT and CR respectively for sixty-three left side breast cancer patients. The 1- and 2-year excellent rate of good cosmetic outcome was both 100%. The 1-, 2- and 3-year local control rate was 99% ,99% and 98% ,respectively. The 1-, 2- and 3-year disease-free survival rate was 99% ,99% and 96% ,respectively. The Grade 1 and 2 acute radiation skin reaction rate was 95.1% and 4.9%, respectively. Conclusion Compared with conventional radiotherapy, IMRT improves dose distribution of CTV and reduce the dose of normal tissue around CTV;but with better clinical effects and lower side-respond for early breast cancer patients after breast conservative surgery.