Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma

Objective：To assess the safety and efficacy of the combination of recombinant adenovirus-p53 （rAd-p53） with radiochemotherapy for treating unresectable pancreatic carcinoma.Methods：The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy.Intratumoral injection of rAd-p53 was guided by B ultrasound.Radiochemotherapy consisted of intensity-modulated radiotherapy （IMRT） at two dose levels and intravenous gemcitabine （Gem）.For radiotherapy,gross target volume （GTV） and clinical target volume （CTV） were 55-60 Gy and 45-55 Gy in 25-30 fractions,respectively.Concurrent intravenous gemcitabine was administered at 350 mg/m2,weekly,for 6 weeks.The primary end points included toxicity,clinical benefit response （CBR） and disease control rate （DCR）.The secondary end points included progression-free survival （PFS） and overall survival （OS）.Results：Fifteen eligible patients were enrolled.Eight patients （53.3%） were evaluated as CBR and 12 （80%） achieved DCR.The median PFS and OS were 6.7 and 13.8 months,respectively.One-year PFS and OS were 40.0% and 51.1%,respectively.There were 8 （53.3%） patients reported grade 3 toxicities including neutropenia （6 patients,40%）,fever （1 patient,6.7%） and fatigue （1 patient,6.7%）.There was no grade 4 toxicity reported.Conclusion：Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated.Long-term follow-up is needed to confirm the improvement of PFS and OS.

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer

BACKGROUND Albumin-bound paclitaxel(ABP)has been used as second-and higher-line treatments for advanced esophageal cancer,and its efficacy and safety have been well demonstrated.Lobaplatin(LBP)is a third-generation platinum antitumor agent;compared with the first two generations of platinum agents,it has lower toxicity and has been approved for the treatment of breast cancer,small cell lung cancer,and chronic granulocytic leukemia.However,its role in the treatment of esophageal cancer warrants further investigations.AIM To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy(RCT)for locally advanced esophageal cancer.METHODS Patients with pathologically confirmed advanced esophageal squamous cell carcinoma(ESCC)at our hospital were enrolled in this study.All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT:ABP 250 mg/m^(2),ivgtt,30 min,d1,every 3 wk;and LBP,30 mg/m^(2),ivgtt,2 h,d1,every 3 wk.A total of four cycles were scheduled.The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions,1.8-2.0 Gy/fraction,and 5 fractions/wk.RESULTS A total of 29 patients were included,and 26 of them completed the treatment protocol.After the induction chemotherapy,the objective response rate(ORR)was 61.54%,the disease control rate(DCR)was 88.46%,and the progressive disease(PD)rate was 11.54%;after the concurrent RCT,the ORR was 76.92%,the DCR was 88.46%,and the PD rate was 11.54%.The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo.Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone(P=0.0024).Non-hematologic toxicities were tolerable,and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis(13.79%).The main hematologic toxicity was neutropenia,and no grade 4 adverse event occurred.CONCLUSION Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC,with mild adverse effects.Thus,this protocol is worthy of clinical promotion and application.

Elderly Lung Cancer Patients and Radiochemotherapy: A Review

More than 60% of lung cancer patients in Europe and the USA are older than 65 years at the time of diagnosis. Despite this, elderly patients are generally under-represented in clinical trials. That being so, a general consensus on how to treat elderly patients is still far from being achieved. In this review, we address some of the issues and challenges surrounding the treatment of older cancer patients and radiochemotherapy. We discuss the existing evidence related to radio-chemotherapy in the elderly, focusing primarily on the lung cancer (NSCLC and SCLC) most commonly seen in older patients, and making general treatment recommendations.

Effect of cisplatin-based concurrent radiochemotherapy on malignant degree of advanced cervical cancer and expression of proto-oncogene and tumor suppressor genes

Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.

Effects of preoperative concurrent radiochemotherapy on the cancer cell infiltration and angiogenesis in local advanced gastric cancer lesions

Objective: To study the effects of preoperative concurrent radiochemotherapy on the cancer cell infiltration and angiogenesis in local advanced gastric cancer lesions. Methods: A total of 68 patients who were diagnosed with locally advanced gastric cancer in this hospital between February 2015 and April 2017 were selected as the research subjects and randomly divided into two groups, the radiochemotherapy group received capecitabine + cisplatin chemotherapy combined with intensity modulated radiation therapy before operation, and chemotherapy group received preoperative capecitabine + cisplatin chemotherapy. The gastric cancer lesions surgically removed from two groups of patients were collected to determine the expression of proliferation-related genes, invasion-related genes and angiogenesis-related genes. Results:Rab27B, Bax, Caspase-3, PTPN13, E-cadherin and THBS2 protein expression in gastric cancer lesions of radiochemotherapy group were greatly higher than those of chemotherapy group whereas EZH2, PRR1, EPHA2, HDAC5, N-cadherin, Twist1, ANGPTL2, ANGPTL5, GOLPH3 and HIF-1 protein expression were greatly lower than those of chemotherapy group. Conclusion: Preoperative concurrent radiochemotherapy has inhibitory effect on the cancer cell infiltration and angiogenesis in local advanced gastric cancer lesions.

Neoadjuvant-intensified treatment for rectal cancer:Time to change?

AIM:To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer.METHODS:Between January 2007 and December 2011,80 patients with histologically confirmed rectal adenocarcinoma were enrolled.Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes.Patients received intensified combined modality treatment,consisting of neoadjuvant radiation therapy(50.4-54.0 Gy) and infusional chemotherapy(oxaliplatin 50 mg/m 2) on the first day of each week,plus five daily continuous infusions of fluorouracil(200 mg/m 2 per die) from the first day of radiation therapy until radiotherapy completion.Patients received five or six cycles of oxaliplatin based on performance status,clinical lymph node involvement,and potential risk of a non-sphincter-conserving surgical procedure.Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment;adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes.After treatment,all patients were monitored every three months for the first year and every six months for the subsequent years.RESULTS:Of the 80 patients enrolled,75 patients completed the programmed neoadjuvant radiochemotherapy treatment.All patients received the radiotherapy prescribed total dose;five patients suspended chemotherapy indefinitely because of chemotherapyrelated toxicity.At least five cycles of oxaliplatin were administered to 73 patients.Treatment was well tolerated with high compliance and a good level of toxicity.Most of the acute toxic effects observed were classified as grades 1-2.Proctitis grade 2 was the most common symptom(63.75%) and the earliest manifestation of acute toxicity.Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients(3.75%).Seventy-seven patients underwent surgery;low anterior resection was performed in 52 patients,Miles' surgery in 11 patients and total mesorectal excision in nine patients.Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors.Out of 75 patients surviving surgery,67 patients(89.33%) had some form of downstaging after preoperative treatment.A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response(stage ypT1ypN0) in six patients.An involvement of the radial margin was never present.During surgery,intra-abdominal metastases were found in only one patient(1.25%).Initially,45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge.Of these patients,only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup.Fourteen patients received postoperative chemotherapy.In the full analysis of enrolled cohort,eight of the 80 patients died,with seven deaths related to rectal cancer and one to unrelated causes.Local recurrences were observed in seven patients(8.75%) and distant metastases in 17 cases(21.25%).The fiveyear rate of overall survival rate was 90.91%.Using a median follow-up time of 28.5 mo,the cumulative incidence of local recurrences was 8.75%,and the overall survival and disease-free survival rates were 90.00% and 70.00%,respectively.CONCLUSION:The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival,likely due to an increase in local tumor control.

Characterization of 500 Chinese patients with cervical esophageal cancer by clinicopathological and treatment outcomes

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

Future therapies for pancreatic carcinoma:Insights into cancer precision medicine

Pancreatic carcinoma(PC)has one of the highest rates of cancer-related death worldwide.Except for surgery,adjuvant chemotherapy,chemoradiotherapy,and immunotherapy have shown various efficacies depending on the stage of the patient.We read the review“Current and emerging therapeutic strategies in pancreatic cancer:Challenges and opportunities”and offer some opinions that may improve its precision and completeness.This review presents a map of appropriate therapies for PC at different stages.Based on the clinical trial outcomes mentioned in the review,we evaluated the potential therapeutic options for PC and helped explain the contradictory efficacy between different programmed cell death protein 1/programmed cell death ligand 1 clinical trials,which may have resulted from the unique features of PC.Although R0 resection and adjuvant chemotherapy are still the gold standards for PC,new modalities,with or without clinical validation,are needed to establish more specific and precise treatments for PC.

The Survival of Head and Neck Carcinoma Patients Depends on Secondary Causes of Death

Purpose: The study aimed to analyse causes of death and differential survival after multimodal treatment of head and neck carcinoma patients. Methods and Materials: Between September 2000 and December 2015, 935 patients received a multimodal treatment of head and neck carcinoma. Of these, 562 patients (60.1%) underwent a resection of the primary tumour and a postoperative radio- or radiochemotherapy and 373 patients (39.9%) received definitive radio- or radiochemotherapy. The median follow-up was 21.0 months (0.5 - 175.4 months). Results: At the endpoint of the investigation, 465 patients (49.7%) were alive. The median survival of all patients was 44.8 months (0.5 - 164.3 months). A total of 470 patients (50.3%) died. The causes of death were divided into five groups: 22 patients (2.4%) died of therapy-associated complications with a median of 2.2 months (1.6 - 3.3 months). The 160 patients (17.1%) with intercurrent death, 117 patients (12.5%) with deaths from locoregional progression with or without metastasis, and 86 patients (9.2%) with deaths from metastasis without locoregional recurrence showed comparable survival curves with a median survival of 13.3 months, 13.6 months, and 14.4 months. Eighty-five patients (9.1%) died from second malignant diseases and controlled treated head and neck carcinomas with a median survival of 34.5 months (P < 0.001). Conclusion: Despite a locoregional control and metastasis-free survival of 78.3% patients, only 49.7% of the patients were alive, due to a high rate of intercurrent and second malignant diseases. The short median survival rate is mainly due to the tumours (locoregional and or distant progression) and intercurrent causes of death, with the second malignant diseases leading to death later on.