We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

Gastrointestinal cancer and related treatments (surgery and chemoradiotherapy) are associated with declined functional status (FS) that has impact on quality of life, clinical outcome and continuum of care. Psychological distress drives an impressive burden of physiological and psychiatric conditions in oncologic care. Cancer patients often experience anxiety, depression, low self-esteem and fears of recurrence and death. Cancer prehabilitation is a process from cancer diagnosis to the beginning of treatment, which includes psychological, physical and nutritional assessments for a baseline functional level, identification of comorbidity, and targeted interventions that improve patient's health and functional capacity to reduce the incidence and the severity of current and future impairments with cancer, chemoradiotherapy and surgery. Multimodal prehabilitation program encompasses a series of planned, structured, repeatable and purposive interventions including comprehensive physical exercise, nutritional therapy, and relieving anxiety and depression, which integrates into best perioperative management ERAS pathway and aims at using the preoperative period to prevent or attenuate the surgery-related functional decline, to cope with surgical stress and to improve the consequences. However, a number of questions remain in regards to prehabilitation in gastrointestinal cancer surgery, which consists of the optimal makeup of training programs, the timing and approach of the intervention, how to improve compliance, how to measure functional capacity, and how to make cost-effective analysis. Therefore, more high-level evidence-based studies are expected to evaluate the value of implementation of prehabilitation into standard practice.
Chemoradiotherapy/adverse effects* ; Digestive System Surgical Procedures/psychology* ; Gastrointestinal Neoplasms/therapy* ; Humans ; Preoperative Care ; Preoperative Exercise ; Quality of Life ; Recovery of Function

BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. METHODS: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. RESULTS: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. CONCLUSIONS On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.
Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; radiotherapy ; Chemoradiotherapy ; adverse effects ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; blood ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-17 ; blood ; Male ; Middle Aged ; Radiation Pneumonitis ; blood ; etiology

OBJECTIVETo assess the effect of Qingfei Quyu Decoction (QQD) in preventing radiation pneumonitis in esophageal carcinoma patients by concurrent using it with chemoradiotherapy.

METHODSA total of 120 patients with mid-late stage esophageal carcinoma were randomly assigned to the treatment group (60 cases) and the control group (60 cases). All patients received concurrent radiochemotherapy. Patients in the treatment group additionally took QQD, one dose per day for 8 successive weeks. The incidence of radiation pneunonitis was compared between the two groups. The improvement rates of short-term benefit rate, Karnofsky performance scale (KPS), and body weight (BW) improvement rate were calculated between the two groups. The 1-and 2-year overall survival rates were compared between the two groups.

RESULTSThe incidence of radiation pneunonitis was 8.93% (15/56) in the treatment group and 18.64% (11/59) in the control group (P < 0.05). The short-term benefit rate was 92.86% (52/56) in the treatment group and 69.49% (41/59) in the control group (P < 0.05). Besides, the KPS and BW improvement rate were higher in the treatment group [89.29% (50/56) and 83.05% (49/59) ] than in the control group [80.36% (45/56) and 66.10% (39/59)] (P < 0.05). The 1-and 2-year overall survival rate were 66.07% and 35.71% in the treatment group, higher than those of the control group (61.02% and 30.51%; P > 0.05).

CONCLUSIONConcurrent using QQD with chemoradiotherapy for treating esophageal carcinoma patients could lower the incidence of radiation pneumonitis, attenuate the degree of radiation induced lung injury, improve clinical benefit rate, and elevate their QOL.

Carcinoma, Squamous Cell ; Chemoradiotherapy ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Esophageal Neoplasms ; drug therapy ; radiotherapy ; Humans ; Radiation Pneumonitis ; prevention & control ; Survival Rate

OBJECTIVETo evaluate the feasibility, safety and short-term clinical outcomes of robot-assisted minimally invasive esophagectomy (RAMIE).

METHODSClinical data of 17 patients with esophageal cancer who received RAMIE between April 2016 and July 2016 were analyzed retrospectively.

RESULTSThe age of the patients ranged from 44 to 83. Six patients received neoadjuvant radiochemotherapy while 11 patients underwent surgery alone. All patients were performed by the robot-assisted thoraco-laparoscopic minimally invasive esophagectomy. In-hospital mortality was 0%. None was converted to open transthoracic or laparotomy approach. In the neoadjuvant radiochemotherapy group, 3 patients received pathological complete response while 2 patients were stage II(A and 1 patient was stage II(B. In the surgery alone group, 1 patient was stage I(A, 3 patients were stage II(A, 5 patients were stage II(B, 1 patient was stage III(A and 1 patient was stage III(B. The mean operation time was 195 minutes (range 145 to 305 minutes). The mean blood loss was 60 ml (range 30 to 200 ml). Mean lymph node harvest was 28 nodes. The rate of radical resection was 100%. Median ICU stay was 4.5 days (range 1 to 36 days), and median overall postoperative hospital stay was 15.2 days(range 9 to 45 days). Postoperative complication occurred in 4 (23.5%) patients, including 3 (17.6%) of lung lesion, 2 (11.8%) of hoarseness, 1 (5.9%) of chylothorax, while no anastomotic leakage and arrhythmia was observed.

CONCLUSIONRAMIE for esophageal cancer is feasible and safe with favorable early outcomes.

Aged ; Aged, 80 and over ; Blood Loss, Surgical ; statistics & numerical data ; Chemoradiotherapy, Adjuvant ; Esophageal Neoplasms ; surgery ; therapy ; Esophagectomy ; adverse effects ; methods ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; surgery ; Middle Aged ; Minimally Invasive Surgical Procedures ; adverse effects ; methods ; Neoadjuvant Therapy ; Operative Time ; Postoperative Complications ; etiology ; Retrospective Studies ; Robotic Surgical Procedures ; adverse effects ; methods ; Thoracic Surgery, Video-Assisted ; adverse effects ; methods ; Treatment Outcome

OBJECTIVE: To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival. METHODS: The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision. RESULTS: The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity. CONCLUSION: The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed.
Adult ; Aged ; Aged, 80 and over ; Brachytherapy ; Carcinoma, Squamous Cell/mortality/*radiotherapy/secondary/virology ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Middle Aged ; Neoplasm Staging ; Papillomavirus Infections/diagnosis ; Radiotherapy/adverse effects ; Republic of Korea ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Tumor Burden ; Vaginal Neoplasms/mortality/pathology/*radiotherapy/virology

BACKGROUND/AIMS: The objective of this study was to assess the prognostic roles of treatment response and tissue necrosis after chemoradiotherapy (CRT) in locally advanced rectal cancer. METHODS: A total of 243 patients with locally advanced rectal cancer who underwent neoadjuvant CRT were included. Three treatment response groups were classified by their pathological stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified based on tissue pathological results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). RESULTS: Overall survival (OS) and recurrence-free survival (RFS) rate at three years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR groups were 83.7%, 75.9%, and 69.7%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p < 0.001). The 3-year OS rates of the CNR, INR, and PNR groups were 83.7%, 80.6%, and 61.8%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p < 0.001). When compared to CTR/CNR, PTR/PNR was strongly related to an increased risk of recurrence (hazard ratio [HR], 5.53; 95% confidence interval [CI], 2.01 to 15.23 vs. HR, 6.37; 95% CI, 2.29 to 17.74, respectively) in univariate Cox regression. Both PTR and PNR were strongly associated with shorter RFS and OS when compared with CTR and CNR in the multivariate Cox regression. CONCLUSIONS: Tissue necrosis is an equally important prognostic marker as treatment response for oncologic outcomes in locally advanced rectal cancer.
Aged ; Biopsy ; *Chemoradiotherapy, Adjuvant/adverse effects/mortality ; Chi-Square Distribution ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; *Laparoscopy/adverse effects/mortality ; Male ; Middle Aged ; Multivariate Analysis ; Necrosis ; *Neoadjuvant Therapy/adverse effects/mortality ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Rectal Neoplasms/mortality/pathology/*therapy ; Remission Induction ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome

To investigate the clinical efficacy of consolidation chemotherapy with docetaxel and cisplatin (DP) in elderly patients of esophageal cancer.
 Methods: Seventy-nine elderly patients of esophageal cancer were randomly divided into the treatment group (38 patients) and the control group (41 patients). Intensity modulated radiation therapy (IMRT) was applied in both groups and prescribed dose was set to 56 to 59.4 Gy in 28 to 33 fractions. The concurrent chemotherapy regime for both groups was as follow: docetaxel 25 mg/m2 plus cisplatin 25 mg/m2, per week. After concurrent chemoradiotherapy, consolidated chemotherapy was applied to the treatment group with docetaxel 60 mg/m2 and cisplatin 75 mg/m2 
for 3 weeks in one cycle. There was no subsequent treatment for the control group.
 Results: The clinical efficacy was assessed in 76 patients. For the treatment group, 31 patients (response rate, 89.2%) obtained effective response, including 10 cases with complete response (CR) and 21 cases with partial response (PR), both of which were significantly more than that in the control group (response rate, 61.5%), with 9 cases of CR and 15 cases of PR. The median progression-free survival was 19.7 months in the treatment group, clearly longer than that in the control group (10.8 months, P=0.04). The overall survival for 1-year, 2-year and 3-year were 78.5%, 57.9% and 37.8% in the treatment group versus 61.2%, 42.3% and 22.7% in the control group (P>0.05), respectively. Grade 1 and 2 adverse effects were commonly observed in both groups, such as hematologic toxicity and radiation-induced esophagitis, but there was no significant difference between the two groups. 
 Conclusion: For elderly patients with esophageal carcinoma, the overall response rate can be significantly improved by concurrent chemoradiotherapy with subsequently consolidated chemotherapy based on docetaxel and cisplatin..
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Chemoradiotherapy ; adverse effects ; Cisplatin ; adverse effects ; Consolidation Chemotherapy ; adverse effects ; Disease-Free Survival ; Docetaxel ; Esophageal Neoplasms ; mortality ; Esophagitis ; epidemiology ; Female ; Hematologic Diseases ; epidemiology ; Humans ; Male ; Radiotherapy, Intensity-Modulated ; adverse effects ; Remission Induction ; Taxoids ; adverse effects

OBJECTIVETo analyze the clinical features and risk factors of anastomotic leakage after radical esophagectomy of esophageal carcinoma.

METHODSThe clinical data of 547 esophageal cancer patients underwent radical esophagectomy in Tianjin Medical University Cancer Hospital from January 2012 to December 2013 was analyzed retrospectively. There were 421 male and 126 female patients, with a median age of 65 years (ranging from 29 to 82 years). There were 155 cases of upper esophageal carcinoma, 340 cases of middle esophageal carcinoma and 52 cases of lower esophageal carcinoma. The surgical procedures included 41 cases completed through Sweet, 145 cases completed through McKeown, 279 cases completed through Ivor Lewis, 82 cases completed through minimally invasive esophagectomy. Moreover, 24 of 547 cases underwent preoperative neoadjuvant radiochemotherapy. χ² test and Cox's proportional hazards regression model were used for univariate analysis and multivariate analysis of the risk factors of postoperative anastomotic leakage.

RESULTSTwenty-seven of 547 cases with esophagectomy occurred anastomotic leakage and the incidence rate was 4.94% (27/547). One of 27 cases died and the mortality rate was 3.70% (1/27). The time of anastomotic leakage found was 4 to 45 days, with a median time of 10 days. There were 0 case of early leakage, 20 cases of mid-term leakage, 7 cases of late leakage. Three of 27 cases with anastomotic leakage had tracheoesophageal fistula, while 3 cases had contralateral pleural fistula. As to the incidence rate of anastomotic leakage, there was statistically significant difference between cervical anastomotic leakage (8.14%, 18/221) and intrathoracic anastomotic leakage (2.76%, 9/326) (χ² =7.41, P=0.000), among Sweet (4.88%, 2/41), McKeown (9.66%, 14/145), Ivor Lewis (2.51%, 7/279) and MIE (4.88%, 4/82) (χ² =21.48, P=0.000), and between with (16.67%, 4/24) and without (4.40%, 23/523) neoadjuvant radiochemotherapy (χ² =9.20, P=0.000). The multivariate analysis showed that anastomotic site (HR=2.594, P=0.048), surgical approach (HR=5.689, P=0.003) and preoperative neoadjuvant radiochemotherapy (HR=3.604, P=0.027) are independent risk factors for anastomotic leakage after esophagectomy.

CONCLUSIONSThe mid-term anastomotic leakage after esophagectomy occurs higher. McKeown is a main surgical procedure and neoadjuvant radiochemotherapy is an important factor for the anastomotic leakage.

Adult ; Aged ; Aged, 80 and over ; Anastomotic Leak ; Carcinoma ; surgery ; Chemoradiotherapy ; Esophageal Neoplasms ; surgery ; therapy ; Esophagectomy ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Retrospective Studies ; Risk Factors