Advances in the therapeutic study of oncolytic virus in colorectal cancer

Colorectal cancer(CRC)represents a considerable global health challenge,ranking third in incidence and second in mortality worldwide.However,existing therapies for diseases with advanced stages often fail,thereby necessitating the search for more comprehensive treatments.Oncolytic virus,a novel anticancer approach,exhibits promising capabilities in selectively targeting and destroying tumor cells while augmenting their efficacy through genetic engineering modifications.Anticipated as a new therapeutic paradigm for CRC,this study aimed to assess the performance of oncolytic virus in clinical trials and explore their potential synergies with other therapeutic modalities,offering insights into the future direction of CRC treatment.

Research progress on lung cancer stem cells in epidermal growth factor receptor–tyrosine kinase inhibitor targeted therapy resistance in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.

Efficacy and safety of berberine in the prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer:a randomized controlled study

Objective The aiom of this study was to study the efficacy and safety of berberine as a prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer.Methods A total of 120 postoperative patients with cervical cancer were enrolled between July 2016 and October 2019,and randomly divided into a treatment group(berberine 300 mg three times a day,n=60)and a control group(receiving vitamin C tablets,100 mg three times a day;n=60)using the random number table method.All patients received pelvic intensity-modulated radiation therapy(IMRT)and concurrent sensitizing chemotherapy weekly.The difference in the percentage of irradiation volume to the rectum and small intestine as well as the incidence,onset time,severity,and duration of acute radiation proctitis and cystitis during radiotherapy were compared between the two groups.The completion rate,completion time,number of chemotherapy sessions,and quality of life during radiotherapy were also compared.Results There were no statistical differences in age,FIGO stage,pathological type,complications,highrisk factors,and rectum and small intestine irradiation dose distribution(V20,V30,V40,and V50)between the two groups(P>0.05).No acute radiation proctitis of grade 3 or above occurred in the two groups.There was no significant difference in the incidence of acute radiation cystitis,grade 2 acute radiation proctitis,completion rate of IMRT,and frequency of sensitization chemotherapy between the two groups.After prophylactic treatment with berberine,the incidence of grade 1 acute radiation proctitis,occurrence of grade 1 radiation proctitis,and completion time of radiotherapy in the treatment group were significantly lower than those in the control group(P<0.05).The SF-36 score of the treatment group after radiotherapy was 67.53±4.21,which was significantly better than that of the control group(64.90±6.32;P<0.05).The incidence of grade 3-4 neutropenia in the treatment group was 10%and lower than that in the control group(31.7%,P=0.003).No adverse reactions related to berberine were observed.Conclusion Prophylactic prescription with oral berberine can reduce the incidence,onset time,and duration of grade 1 acute radiation proctitis,and improve the quality of life of postoperative patients with cervical cancer receiving concurrent chemoradiotherapy.

Chinese experts' consensus on diagnosis, prevention, and treatment of chemotherapyinduced hepatotoxicity

Overview Drug-induced liver injury(DILI)due to acetaminophen overdose and idiosyncratic drug reactions usually occurs 5–90 days after exposure to the causative drug.Ninety percent of DILI cases are acute.As one of the most common non-infectious liver diseases,DILI represents a growing challenge for clinicians.According to data from WHO[1],DILI is the fifth leading cause of liver disease mortality.In China,DILI accounts for 1%–5%of hospitalized patients with liver diseases,10%of patients

A missense variant of MASP2 is associated with increased risk of radiation pneumonitis in lung cancer patients treated with radiation therapy

Objective In this study,mannan-binding lectin-associated serine protease 2(MASP2)gene variant was evaluated to assess the risk of radiation pneumonitis(RP)in patients with pulmonary malignancies.Methods A total of 169 lung cancer patients with radiotherapy were included in our prospective study(NCT02490319)and genotyped using the Sanger sequencing method.Multivariate Cox hazards analysis and multiple testing were applied to estimate the hazard ratio(HR)and 95%confidence intervals(CIs)of all factors possibly associated with RP risk.Results Patients with mean lung disease≥15 Gy and V20≥24%had higher risk of RP≥grade 2 compared with their counterparts(HR=1.888,95%CI:1.186-3.004,P=0.007;HR=2.126,95%CI:1.338-3.378,P=0.001,respectively).Importantly,CC+CA genotype of MASP2:rs12711521 was strongly associated with an increased occurrence of RP≥grade 2(HR=1.949,95%CI:1.278-2.971,P=0.002).Conclusion MASP2:rs12711521 was found to be significantly associated with RP≥grade 2 in our cohort and may thus be one of the important predictors of severe RP before radiotherapy,if further validated in larger population.

Comparable outcomes but higher risks of prolonged viral RNA shedding duration and secondary infection in cancer survivors with COVID-19: A multi-center, matched retrospective cohort study

Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-cancer patient cohort were 64.0(55.0–73.0)and 64.0(54.0–73.5),respectively(P=0.909).Cancer survivors reported a higher incidence of symptom onset than non-cancer patients.Fever(80.3%vs.65.0%;P=0.026)was the most prevalent symptom,followed by cough(65.6%vs.37.7%;P<0.001),myalgia,and fatigue(45.9%vs.13.6%;P<0.001).The risks of the development of severe events(adjusted hazard ratio[AHR]=1.25;95%confidence interval[CI]:0.76–2.06;P=0.378)and mortality(relative risk[RR]=0.90,95%CI:0.79–1.04;P=0.416)in the cancer survivor cohort were comparable to those of the matched non-cancer patient cohort.However,the cancer survivor cohort showed a higher incidence of secondary infection(52.5%vs.30.1%;RR=1.47,95%CI:1.11–1.95;P=0.002)and a prolonged viral RNA shedding duration(32 days[IQR 26.0–46.0]vs.24.0 days[IQR 18.0–33.0];AHR=0.54;95%CI:0.38–0.80;P<0.05).Conclusion Compared to non-cancer patients,cancer survivors with COVID-19 exhibited a higher incidence of secondary infection,a prolonged period of viral shedding,but comparable risks of the development of severe events and mortality.It is helpful for clinicians to take tailored measures to treat cancer survivors with COVID-19.

Recurrent ascites due to spontaneous intraperitoneal bladder rupture after pelvic radiation therapy for cervical cancer

Radiation cystitis is one of the major complications following radiotherapy for cervical cancer. However, spontaneous intraperitoneal bladder rupture as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare. Case presentation: We report a 52-year-old patient who received radiation therapy for cervical cancer 15 years prior to presentation. Eight years prior to presentation, she developed recurrent abdominal distension, oliguria, and ascites. Following ascites drainage and supportive treatment, all symptoms were relieved. However, all symptoms subsequently recurred every few months. The patient underwent exploratory laparotomy twice. The first exploratory laparotomy in July 2015 found no specific abnormalities. The second exploratory laparotomy in November 2016 found an intraperitoneal bladder rupture, and the patient underwent surgical repair. The ascites subsequently resolved. Conclusion: The occurrence of spontaneous intraperitoneal bladder rupture after radiation therapy for cervical cancer is rare. The prognosis is good when diagnosis and treatment are prompt.

Postoperative sequential chemotherapy and radiotherapy for locally advanced gastric cancer

Objective The aim of the study was to evaluate the role of postoperative sequential chemotherapy and radiotherapy in patients with locally advanced gastric cancer.Methods From January 2003 to December 2010, 146 gastric cancer patients at our institution(Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) received postoperative sequential chemotherapy and radiotherapy after radical surgery. Radiotherapy was administered as a dose of 4500 cGy in 25 fractions. For patients with positive margins, the dose was raised to 5040 cGy in 28 fractions. Three cycles of m FOLFOX or PF(cisplatin, 5-fluorouracil) chemotherapy regimen were applied before and after radiotherapy. Three-and 5-year survival rates were analyzed; any adverse effects with respect to hematology, hepatic and renal function, or the gastrointestinal tract that occurred during the treatment were evaluated.Results This cohort consisted of non-metastatic patients: 104 men and 42 women with a median age of 51.0 years. The full course of sequential chemotherapy and radiotherapy(4500–5040 cGy) was completed by 129 patients(88.4%). Seventeen regional relapses(9.8%) and 46 distant relapses(23.8%) were recorded. Fifty patients(34.2%) died during follow-up. The 3-and 5-year overall survival rates(OS) were 60% and 54%, and disease-free survival rates(DFS) were 53% and 47%, respectively. There were no significant differences in survival rate with respect to age, sex, histopathology, N stage, site of the tumor, or margin status. Multivariate analysis showed that only the depth of tumor invasion(T stage) was an independent prognostic factor for OS(P = 0.009) and DFS(P = 0.006). The rates of grades 3 and 4 neutropenia and vomiting were 9.6% and 3.4%, respectively, during the treatment.Conclusion Postoperative sequential chemotherapy with an m FOLFOX or PF regimen and radiotherapy were found to be an effective means of treating advanced gastric cancer patients with T3–T4 disease. The adverse effects of this treatment were tolerable.

Targeted therapy of gastric cancer:current and prospective strategies

Gastric cancer is the third leading cause of cancer-related death worldwide. Surgery is currently the only curative treatment strategy. Chemotherapy has shown limited efficacy in advanced gastric cancer patients with a median overall survival of less than one year. Thus, new treatments are urgently needed. Trastuzumab and Ramucirumab are the only targeted therapies approved currently. Most Phase Ⅲ clinical trials evaluating targeted drugs in gastric cancer have failed. This review will evaluate relevant clinical trials with targeted therapies performed in gastric cancer patients, discuss the possible reasons for the failure, and indicate new possibilities to enhance gastric cancer treatment.

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib

Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.

Common toxicities and objective response rate in metastatic colorectal cancer patients treated with irinotecan based regimens

Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Methods： Univadate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results： The most frequent severe toxicities （Grade 3/4） were as follows： neutropenia （27.4%）, diarrhea （16.9%）, leucopenia （12.6%）, vomiting （3.2%） and thrombocytopenia （2.1%）. Thrombocytosis was observed in 25 （26.3%） patients. ORR was 25.3%. Thrombocytopenia （P = 0.014）, line of chemotherapy （P = 0.028） and thrembocytosis （P = 0.033） were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia （odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705-43.385, P = 0.009） and first line chemotherapy （OR = 5.155, 95% CI = 1.153-23.256, P = 0.032） positively related to ORR. Conclusion： Threm- bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ- ated with ORR.

Clinical characteristics and survival outcomes of perianal Paget’s disease:A SEER population-based study

Objective The aim of the study was to analyze the clinical features of patients with perianal Paget’s disease(PPD)and investigate prognosis risk factors.Methods The SEER*Stat software was used to identify 116 PPD patients from 1975 to 2015 in the SEER research database.The Kaplan-Meier method was used to conduct a univariate analysis for PPD patients.The differences in survival rates were evaluated using the log-rank test.The differences in the clinicopathological features of PPD patients with or without anorectal carcinoma were compared using the chi-square test.Results The median survival time of PPD patients was 44 months.The median age of onset was 73 years old.The 43.10%of the patients were alive at the end of follow up,and only 12.93%of the patients died of PPD.Elderly(age>70 years;χ^2=9.453,P=0.002),poor differentiation(χ^2=46.557,P=0.000)and abdominal perineal resection(APR;χ^2=46.557,P=0.000)were unfavorable risk factors of prognosis.Nearly 50%of PPD had combined with other malignancies,and over 22.41%of those had multiple primary neoplasms(3 or more).PPDs predisposed concurrent malignancy,and 48.21%of PPD patients with other malignancies combined with anorectal carcinoma in the study.Stage(χ^2=10.127,P=0.018),and surgical method(χ^2=12.245,P=0.007)were statistically significant in the PPD patients with or without anorectal carcinoma.The 16.07%of patients had multiple lesions of Paget’s.Conclusion Patients with PPD have a favorable survival,while the disease-specific mortality is low.Diagnosed age,differentiation,and surgical methods were the influence factors of prognosis in PPD patients.PPDs with anorectal carcinoma is of most important in further investigation.

Progress in research on digestive system oncology

Digestive system cancers are common causes of cancer-related deaths.In recent years,many reports on the progress in research on digestive system cancers,from etiology to therapy,have been published.In this column,we mainly introduce the achievements in four different aspects.Human papillomavirus(HPV)is the primary etiologic factor in many malignant tumors such as cervical,anal,and oropharynx cancers.Among 80

Survey of changes in dietary preferences in cancer patients in China

Objective The aim of this study was to investigate the changes in dietary preferences in cancer patients in China and to determine the need for encouraging the adherence to a sensible diet among such patients.Methods A total of 468 cancer patients were interviewed using a self-designed questionnaire focusing on changes in the intake of specific foods. Data were analyzed using SPSS 16.0. Results Most patients completely avoided roosters and carp(73.1%), condiments(51.9%), and meat of aquatic species(40.4%). All other types of the specific foods were completely avoided by different subpopulations of the patients.Conclusion In addition to focusing on disease treatment, medical professionals need to help cancer patients overcome barriers associated with the customs of avoiding specific foods encompassed by the term "fawu" and provide them with dietary guidance in order to prevent negative nutritional effects.

Alpha-fetoprotein-producing rectum adenocarcinoma:A case report

A case with an Alpha-fetoprotein-producing(AFP-producing) carcinoma originating from the rectum was described.A 41-year-old man,who underwent a palliative surgery for rectal carcinoma,was diagnosed with occupying liver lesions and a remarkable AFP elevation(3484.61 ng/mL),and the AFP declined obviously 10 days after the palliative surgery.So we carried out a biopsy of the liver lesions.The histopathology was reported as low differentiation adenocarcinoma.The immunohistochemistry of the tumor cells via liver biopsy showed:Villin,CDX-2 was positive,Glypican-3 was partial positive,CK7,CK20,AFP,Hepatocyte were all negative.The initial histopathology was reported as an AFP-producing rectum adenocarcinoma with liver metastasis,which was a rare disease.So far,only 17 reports,none has been reported in China.Then,we summarize the characteristic of the disease:diagnosed with hepatic metastasis,raised serum AFP and a poor outcome,in addition to primary symptoms.This kind of disease is highly malignant.

Future of targeted therapy for gastrointestinal cancer:Claudin 18.2

The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.

Outcomes of palliative local treatment in metastatic colorectal cancer patients receiving chemotherapy plus bevacizumab

Objective The aim of this study was to assess the value of palliative local treatment of incurable metastatic lesions in colorectal cancer(CRC) patients receiving chemotherapy plus bevacizumab.Methods Data of 105 patients with histologically confirmed synchronous or metachronous metastatic CRC who received bevacizumab treatment from January 1, 2011 to January 31, 2017 were retrospectively reviewed. Sixteen(15%) patients who were treated with bevacizumab for less than 4 cycles were excluded, and finally, 89(85%) patients were enrolled. Among them, 33(37%) patients who received palliative local treatment were categorized into the palliative local treatment group, and the remaining 56(63%) patients were categorized into the chemotherapy plus bevacizumab group. The primary endpoint was overall survival(OS), which was calculated using Kaplan-Meier survival analyses. Factors possibly influencing survival were evaluated by univariate and multivariate analyses. Adverse events(AEs) were graded according to Common Terminology Criteria for Adverse Events, version 4.0. Grades 1–2 and 3–4 AEs of the two groups were compared and analyzed using the Fisher's exact test and χ~2 analysis.Results The median follow-up period was 20.4 months, ranging from 1 to 60 months. The median OS in the palliative local treatment group was 36.3 months(95% CI, 33.5–39.2), and that in the chemotherapy plus bevacizumab group was 20.5 months(95% CI, 17.6–23.4). Both the univariate(HR 0.13, 95% CI, 0.05–0.30, P < 0.001) and multivariate(HR 0.16, 95% CI, 0.07–0.39, P < 0.001) analyses showed that the addition of palliative local treatment could prolong survival compared with chemotherapy plus bevacizumab alone. There were no significant differences in the rates of common chemotherapy-or bevacizumab-related AEs between the two groups.Conclusion These findings suggest palliative local treatment is an effective and safe method for treating patients with incurable metastatic CRC receiving chemotherapy plus bevacizumab.

Seroprevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in patients with cancer and the impact of anti-tumor treatment on antibodies

Objective The aim of this study was to examine the seroprevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among patients with cancer and followed up changes in SARS-CoV-2-specific antibodies to explore the impact of anti-tumor treatment in patients.Methods Patients with cancer who visited the Outpatient Clinic of Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China between March 9 and April 30,2020 were enrolled in this retrospective cohort study.SARS-CoV-2 immunoglobulin(Ig)G,IgM,and viral load at various time points during the disease course were determined.Results We examined the serological results of 779 patients with cancer.The overall seroprevalence(IgG-positive or IgM-positive)rate of SARS-CoV-2 was 3.4%.The probability of seropositivity was significantly higher in patients with gastric cancer than in those without gastric cancer(odds ratio:6.349,95%confidence interval:2.191–18.396).Follow-up data showed that SARS-CoV-2 IgM and IgG levels decreased and the polymerase chain reaction test result remained negative in seropositive patients with cancer.Conclusion This study investigated the seroprevalence of SARS-CoV-2 in coronavirus disease(COVID-19)-positive patients with cancer in Wuhan,China.The seropositivity in patients with cancer was lower than or similar to that in the general population.Irrespective of anti-tumor therapy,the levels of SARS-CoV-2 antibodies decreased in these patients.More studies are needed to better understand the impact of anti-tumor therapy on change in the levels of SARS-CoV-2 antibodies.

Treatment of aggressive pancreatic solid pseudo-papillary neoplasms with apatinib plus S-1 chemotherapy:A case report and literature review

Solid pseudopapillary neoplasm(SPN) is a rare indolent pancreatic neoplasm that occurs mostly in females. Although the malignancy potential is quite limited for SPN, these tumors can sometimes be aggressive and lead to inferior prognosis for male patients. In this case report, we present a special case of a male patient with SPN who experienced an aggressive tumor expansion after two surgical resections. For further treatment, we decided to administer chemotherapy with apatinib and S-1, and subsequent CT/MRI tumor monitoring indicated satisfactory control of tumor expansion. The effectiveness of apatinib plus the S-1 regimen should be tested for more patients with SPN in the future.

EDGE non-invasive radiosurgery for gastric neuroendocrine hepatic portal lymph node metastases:a case report

Treating metastatic gastric neuroendocrine neoplasms （gNENs） is challenging, especially for those with progressive disease during somatostatin analog processing. In this report, we present a case of a welldifferentiated grade 2, type 3 gNEN with metastatic hepatic portal lymph nodes. EDGE non-invasive radiosurgery （800 cGy x 5 F） was performed to radiate the metastatic hepatic portal lymph nodes. Three months after the hyperfractionated radiotherapy, no signs of metastatic hepatic portal lymph nodes were observed using 8Ga-dotatate positron emission tomography-computed tomography or magnetic resonance imaging. Therefore, EDGE non-invasive radiosurgery could be a potential option for treating local metastatic nodes.