Both carcinoembryonic antigen and CA19-9 are considered as predictive markers of intestinal cancer recurrence and metastasis.In addition,CA19-9 elevation is considered as a predictive marker of connective tissue disease-related interstitial lung disease.The incidence of oxaliplatin and capecitabine-associated interstitial lung disease is low,and there is no report about CA19-9 as a predictive marker of oxaliplatin and capecitabine-associated interstitial lung disease.This paper reports a case of interstitial lung disease with CA19-9 elevation caused by oxaliplatin and capecitabine adjuvant therapy for ileocecal carcinoma.The change trend of serum carcinoembryonic antigen in this patient was consistent with tumor recurrence and metastasis,and that of serum CA19-9 was consistent with the severity of interstitial lung disease.Therefore,CA19-9 elevation after intestinal cancer surgery does not necessarily indicate the tumor recurrence and metastasis,and attention should be paid to the possibility of oxaliplatin and capecitabine-associated interstitial lung disease.
Humans ; CA-19-9 Antigen/blood* ; Capecitabine ; Cecal Neoplasms/drug therapy* ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage* ; Fluorouracil/administration & dosage* ; Lung Diseases, Interstitial/blood* ; Organoplatinum Compounds/administration & dosage* ; Oxaliplatin

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.
Adenocarcinoma/therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Capecitabine/administration & dosage* ; Chemoradiotherapy, Adjuvant ; Esophagogastric Junction/surgery* ; Gastrectomy ; Humans ; Lymph Node Excision ; Neoadjuvant Therapy ; Neoplasm Staging ; Oxaliplatin/administration & dosage* ; Prognosis ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms/therapy*

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.
Adenocarcinoma/surgery* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Capecitabine/administration & dosage* ; Chemotherapy, Adjuvant ; Drug Combinations ; Humans ; Neoadjuvant Therapy ; Oxaliplatin/administration & dosage* ; Oxonic Acid/administration & dosage* ; Radiotherapy ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Tegafur/administration & dosage* ; Treatment Outcome

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.
Adenocarcinoma/surgery* ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant ; Dissection ; Drug Combinations ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Male ; Middle Aged ; Neoplasm Staging ; Oxaliplatin/administration & dosage* ; Oxonic Acid/administration & dosage* ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Tegafur/administration & dosage* ; Treatment Outcome