Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial / 中华胃肠外科杂志

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

TGF-beta1 in serum and induced sputum for predicting radiation pneumonitis in patients with non-small cell lung cancer after radiotherapy / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Research has confirmed that transforming growth factor-beta1 (TGF-beta1) is one of the cytokines related to radiation pneumonitis. But the level of TGF-beta1 in serum needed to predict radiation pneumonitis is still not clear. This study assessed the value of TGF-beta1 in both serum and induced sputum in predicting radiation pneumonitis, providing a reference for the radiotherapy of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 23 patients with NSCLC treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in our department between November 2007 and January 2009 were analyzed and evaluated. TGF-beta1 levels in both serum and sputum were detected before and near the end of radiotherapy for all the patients. The TGF-beta1 level in serum was measured with enzyme-linked immunosorbent assay (ELISA). Immunocytochemistry assays were used to detect TGF-beta1 expression in sputum sediment. Radiation pneumonitis was graded according to Radiation Therapy Oncology Group (RTOG) radiation scoring criteria every 3 weeks from the start to 3 months after the end of treatment.</p><p><b>RESULTS</b>Radiation pneumonitis was noted in 9 patients in this cohort. The total incidence of radiation pneumonitis was 39.1% (9/23) and those with Grade II or worse was 30.4% (7/23). The absolute TGF-beta1 level in serum after radiotherapy was higher than before radiotherapy, but there was no statistical difference (P = 0.139). Patients with increased levels of TGF-beta1 had a higher incidence of radiation pneumonitis (45.5%) than those with decreased TGF-beta1 levels post-radiotherapy (40.0%). Though there was a tendency of higher incidence of radiation pneumonitis with increases in TGF-beta1 level, no statistical difference was found (P = 1.000). Patients with tumor response had higher incidence of radiation pneumonitis (50.0%) than patients without when TGF-beta1 levels in serum increased, but there was no statistical difference (P = 0.792). TGF-beta1 was positively expressed (brown yellow) in sputum on immunocytochemistry assays and located in the cytoplasm of either macrophages or epithelial cells. Macrophages were the main cells expressing TGF-beta1. A significantly higher positive expression rate (71.4%) was found in sputum post-radiotherapy than pre-radiotherapy (28.6%) (P = 0.015). The higher incidence of radiation pneumonitis (46.7%) was found in patients with positive TGF-beta1 expression in sputum post-radiotherapy than those with negative expression post-radiotherapy (14.3%) (P = 0.193).</p><p><b>CONCLUSION</b>It may be more reasonable to predict radiation pneumonitis by combining the change of TGF-beta1 levels in serum with tumor response than just the change of TGF-beta1 levels in serum alone. TGF-beta1 can positively express in the sputum of patients with NSCLC, located in macrophages and epithelial cells, with macrophages as the main areas of expression. Patients with positively expressed TGF-beta1 in sputum after radiotherapy have a higher incidence of radiation pneumonitis than those with negative expressions. The positive expression of TGF-beta1 in sputum is expected to become a factor for predicting radiation pneumonitis.</p>

The value of radiotherapy in patients with T1 and T2 breast cancer with one to three positive nodes after modified radical mastectomy / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The role of adjuvant radiotherapy to the regional nodes in women with T1 to T2 breast cancer and one to three positive nodes is controversial. This study compared and analyzed the prognosis of patients with T1-T2 breast cancer with one to three positive nodes after modified radical mastectomy with or without postoperative radiotherapy.</p><p><b>METHODS</b>The cases of 434 women patients with T1 to T2 breast cancer with one to three positive lymph nodes after modified radical mastectomy were reviewed, of which 196 patients received postoperative radiotherapy and 238 patients did not. The ipsilateral chest wall and supraclavicular fossa were irradiated with doses of 46-50 Gy in 23-25 fractions.</p><p><b>RESULTS</b>For all patients, the 3- and 5-year rates of overall survival (OS) were 94.7% and 85.7% respectively, local control (LC) 96.5% and 95.6%;, and disease-free survival (DFS) 89.3% and 82.3% respectively. The 3- and 5-year OS rates for patients without radiotherapy were 92.7% and 97.1% and for those with radiotherapy were 82.4% and 89.2%, both with significant differences (P = 0.039). The 3- and 5-year LC rates for patients without radiotherapy were 94.8% and 98.4% and for those with radiotherapy were 93.6% and 97.7%, again with significant differences (P = 0.041). The 3- and 5-year DFS rates for patients without radiotherapy were 87.8% and 91.3% and for patients with radiotherapy were 78.5% vs 86.1% (P = 0.047).</p><p><b>CONCLUSIONS</b>Postoperative radiotherapy confers better rates of OS, LC, and DFS in patients with T1 to T2 breast cancer with one to three positive nodes after modified radical mastectomy.</p>

Literature analysis of radiotherapy for esophageal cancer in China / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Many patterns of treatment have been used to treat esophageal carcinoma in the past years, however, an optimal treatment is still the key issue to be explored. Therefore, we analyzed the published literature about radiotherapy for esophageal cancer in recent 15 years in China, and observed the survival rate, local control rate, adverse events, and so on.</p><p><b>METHODS</b>A total of 56 eligible papers about radiotherapy for esophageal squamous cell carcinoma published in Chinese core periodicals between 1994 and 2009 were selected. The survival rates, local control rates, and adverse events were analyzed.</p><p><b>RESULTS</b>The 1-, 2-, 3-, and 5-year overall survival rates of the patients reported in the 56 papers were (67.99 ± 12.55)%, (49.59 ± 11.79)%, (34.50 ± 11.49)%, and (23.31 ± 10.21)%, respectively. The 1-, 2-, 3-, and 5-year local control rates were (73.04 ± 13.37)%, (61.60 ± 15.50)%, (51.77 ± 15.00)%, and (50.15 ± 21.36)%, respectively. The acute esophageal toxicity rate was (44.84 ± 25.71)% in 32 papers reported in recent 15 years, and the acute esophageal toxicity over grade II accounted for (35.93 ± 22.90)%. The rates of acute esophageal toxicity were (26.84 ± 13.12)% for conventional radiation, (53.72 ± 21.82)% for late course accelerated hyperfractionation radiation, (61.33 ± 28.69)% for concurrent chemoradiotherapy, and (40.31 ± 27.22)% for other ways of radiation. The late toxicity rate described in 23 papers was (5.13 ± 4.07)% in recent 15 years. The late toxicity rates were (5.66 ± 3.42)% for conventional radiation, (4.53± 4.07)% for late course accelerated hyperfractionation radiation, (2.24±1.31)% for concurrent chemoradiotherapy, and (7.34 ± 5.06)% for other ways of radiation. The Meta analysis indicated that concurrent chemoradiotherapy was better than late course accelerated hyperfractionation radiation and conventional radiation.</p><p><b>CONCLUSIONS</b>The long-term survival of patients with esophageal cancer is still disappointed in recent years. Concurrent chemoradiotherapy shows advantages in treating esophageal cancer and, currently, is the best non-surgical treatment of esophageal cancer.</p>

Association of single nucleotide polymorphism of MnSOD gene with carcinogenesis and development of esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphism (SNP) of manganese superoxide dismutase (MnSOD) gene with carcinogenesis and progression of esophageal squamous cell carcinoma.</p><p><b>METHODS</b>The MnSOD9 T-->C SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 103 patients with esophageal squamous cell carcinoma and 195 healthy controls.</p><p><b>RESULTS</b>A significant difference was observed in the MnSOD allelotype distribution among esophageal squamous cell carcinomas and healthy controls (chi(2) = 4.645, P < 0.05). Individuals with the 9 C allele had a significantly higher risk to develop esophageal squamous cell carcinoma compared with those with the TT allele. The frequency of C allelotype among patients with lesions of different lengths (</= 5 cm and > 5 cm) was 16.3% and 36.7%, respectively. A significant difference was observed in the MnSOD allelotype distribution between patients with lesions of different lengths (chi(2) = 5.147, P < 0.05). No significant association of the MnSOD polymorphism at 9 T-->C with the tumor site, maximal length and clinical staging was found in esophageal squamous cell carcinoma.</p><p><b>CONCLUSION</b>Single nucleotide polymorphism (SNP) of MnSOD gene may be correlated with the susceptibility and disease progression of esophageal squamous cell carcinoma, and may become a tumor marker for prediction of this cancer.</p>

Portal size of prophylactic postoperative radiotherapy for esophageal carcinoma / 中华放射肿瘤学杂志

Objective To compare and analyze the effect of prophylactic postoperative radiotherapy for esophageal carcinoma.Methods 102 such patients were treated with prophylactic radiotherapy after radical resection,to a total dose of 50-60 Gy.The extensive portal included supraclavicular region on both sides,entire mediastinum,the site of anastomosis and left gastric lymph node region in 43 patients.The re- gional portal range was different according to the different location of primary lesion in 59 patients.Results The 1-,3- and 5-year survival rate was 76%,51% and 43% respectively,with a median survival of 30 months.The 1-,3- and 5-year survival rate was 77%,52% and 41% in the extensive portal and 76%, 49% and 45% in the regional portal,respectively(P=0.884).According to multivariate analysis,N stage, number of metastatic lymph nodes and tumor length were independent prognostic factors.Conclusions Regional portal does not lower the survival rate when prophylactic postoperative radiotherapy is used in e- sophageal carcinoma.

Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma / 中华放射肿瘤学杂志

Objective To define the maximum-tolerated dnse(MTD)and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese,with toxicity studied.Methods Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionafiun radiotherapy,with 5 daily fractions of 2.0 Gy per week.The total radiation dose was 60 Gy.Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence.The starting dose was cisplatin 37.5 mg/m~2 D1 and 5-fluorouracil 500 mg/m~2 D1-5, respectively.This regimen was repeated 4 times every 28 days.Escalation dose was eisplatin 7.5mg/m~2 and 5- fluorouracil 100mg/m~2.Every cohort contained at least 3 patients.If no dose-limiting toxicity(DLT)was observed, the next dose level was opened for entry.These courses were repeated until DLT appeared.MTD was declared as one dose level below which DLT appeared.Results DLT was defined as grade 3 radiation-induced esophngitis at the level of cisplatin 60 mg/m~2,5-fluorouracil 700 mg/m~2.MTD was defined as eisplafin 52.5 mg,/m~,5- fluorouracil 700 mg/m~2.The major side effect were radiation-induced esophagitis,leucopenia,nausea,vomiting and anorexia.Conclusion Maximun tolerated dose of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m~2 D1,5-fluorouracil 700 mg/m~2 D1-5,repeated 4 times every 28 days.