A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.

Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel

Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry

Weight Loss and Gastrointestinal Symptoms in Advanced Cancer Patients Treated with Platinum-based Chemotherapy

Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.

Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors

In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

Objective： Data on the clinical activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in patients with non-small-cell lung cancer （NSCLC） and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods： We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results： Seventy patients （13.9%） harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate （ORR） and median progression-free survival （mPFS） of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group （ORR： 23.3% vs. 51.8%, P=0.003; mPFS： 7.1 vs. 10.9 months, P〈0.001）. In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy （7.1 vs. 6.1 months, P=0.893）. In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant （G719X： 8.2 vs. 5.8 months, P=0.061; L861Q： 7.6 vs. 4.1 months, P=0.872）. Multivariate analyses identified adenocarcinoma （P=0.003） as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions： The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR- TKIs.

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients suffer.The mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients.In this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.Methods:A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study.Toxicity was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.Results:MutS homolog 2[MSH2) rs6544991[odds ratio(OR) 2.98,95%confidence interval(CI) 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627(OR 2.38,95%CI 1.23-4.60,P = 0.010),rs6151670(OR 2.05,95%CI 1.07-3.93,P = 0.031),and rs7709909(OR 2.38,95%CI 1.23-4.64,P = 0.010)were associated with hematologic toxicity in the dominant model.Additionally,MSH5 rs805304 was significantly associated with overall toxicity(OR 2.21,95%CI 1.19-4.09,P = 0.012),and M5H5 rs707939 was significantly associated with both overall toxicity(OR 0.42,95%CI 0.23-0.76,P = 0.004) and gastrointestinal toxicity(OR 0.44,95%CI 0.20-0.96,P = 0.038) in the dominant model.Conclusion:Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.

The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival(OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian(predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs(r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations(r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations(r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

Mutations in the DNA polymerase binding pathway affect the immune microenvironment of patients with small-cell lung cancer and enhance the efficacy of platinum-based chemotherapy

Background:Small-cell lung cancer(SCLC)is characterized by its high malignancy and is associated with a poor prognosis.In the early stages of the disease,platinum-based chemotherapy is the recommended first-line treatment and has demonstrated efficacy.However,SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages.Methods:Here,we collected samples from SCLC patients who received platinum-based chemotherapy,performed genomic and transcriptomic analyses,and validated our results with publicly available data.Results:SCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations.Patients in the mutant(MT)group had higher infiltration of T cells,B cells,and M1 macrophages compared with patients without DNA polymerase binding pathway mutations.Conclusions:DNA polymerase binding pathway mutations can be used as prognostic markers for platinum-based chemotherapy in SCLC.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Targeting glutamine metabolism enhances responses to platinum-based chemotherapy in triple-negative breast cancers(TNBC)

Reprogramming of metabolic pathways,a hallmark of human cancer,results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and survival.Previous studies have demonstrated that triplenegative breast cancers(TNBC)may use glutamine as an extracellular nutrient source to generate lipids,proteins,and nucleic acids.1 Glutamine catabolism in cancer cells also contributes to the production of the antioxidant,glutathione(GSH),which is critical for redox homeostasis and for protection of cells from oxidative stress elicited by reactive oxygen species(ROS).2 Considering TNBC cell lines are often dependent on glutamine for growth and survival,we sought to determine whether targeting glutaminolysis with a small molecule inhibitor,CB-839,in combination with platinum-based chemotherapy drug,would elicit significant anti-tumor activity.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Screening of Myocardial Cardiotoxicity Induced by Anticancer Chemotherapy and the Importance of Global Longitudinal Strain

Introduction: The improvement of survival in patients with cancer and the expansion of therapeutic options have led to the emergence of a new profile of cardiotoxicity, specifically associated with antimitotic agents. Our study aimed to assess the incidence of chemotherapy-induced myocardial toxicity in patients with cancer. Patients and Methods: We conducted a looking-forward longitudinal cohort study including all patients admitted to the Cardiology departments of Aristide le Dantec Hospital and Dalal Jamm National Hospital Centre for apre-chemotherapy check-up. The included patients did not undergo any pre-existing cardiopathy. Results: Over a period of two years ranging from January 2019 to December 2021, a total of 37 patients were included in the study. Notably, there was a female predominance (92%) with an average age of 49.7 years ± 13.69. Breast cancer accounted for 70% of the neoplasms. Laboratory findings revealed moderate anemia in 19 patients (51%). At inclusion, the left ventricle (LV) was of normal size (LV diastole at 44.46 ± 4.97 mm). The systolic function of the left ventricle was normal in all patients, with an average ejection fraction (EF) of 63.1% ± 5.80 and a mean global longitudinal strain (GLS) of −20.4% ± 2.58. The most commonly used agents were anthracyclines. During follow-up, 3 patients (8.1%) developed clinical symptoms of left heart failure, and LV dysfunction on echocardiography was observed in 5 (13.5%) patients, with a significant decrease in EF Conclusion: The incidence of cardiac toxicity is not negligible, hence the importance of early screening. Strain imaging is an essential tool that should be performed as part of the assessment before chemotherapy and re-evaluated during treatment.

Perioperative chemotherapy improves survival of patients with locally advanced diffuse gastric cancer

BACKGROUND Whether patients with diffuse gastric cancer,which is insensitive to chemo-therapy,can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial.AIM To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer.METHODS A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed.RESULTS Compared with surgery alone,perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer.Before stabilized inverse probability of treatment weighting(IPTW),the median overall survival(OS)times were 40.0 months and 13.0 months(P<0.001),respectively.After IPTW,the median OS times were 33.0 months and 17.0 months(P<0.001),respectively.Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW.After IPTW,the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group(P=0.472).CONCLUSION Patients with diffuse gastric cancer can benefit from perioperative chemotherapy.There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received adjuvant chemotherapy.

Nutritional Supplement Ocoxin® Combined with Gemcitabine-Based Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma

Background: the quality of life (QoL) of patients with pancreatic ductal adenocarcinoma (PDAC), with its limited survival, can be affected by chemotherapy-induced toxicity. The main objective was to evaluate the effect of introducing ocoxin oral solution (OOS) in combination with standard therapy on quality of life. Methods: Thirty patients were enrolled in an exploratory, prospective, single-centre clinical trial in the oncology department of “Hermanos Ameijeiras” University Hospital in Havana, Cuba. Quality of life was measured using the EORTC QLQ-C30 questionnaire and toxicity was assessed using the NCI-CTC-AE classification version 5.0. Results: There was stability in the scores over time for overall QoL and the functional scale criteria, while in terms of symptoms, fatigue, pain and loss of appetite were reduced. No grade 3 - 4 adverse events (AEs) were recorded, and only 14.9% of toxicities were classified as grade 2, and these were considered to be unrelated to OOS. Biochemical and nutritional parameters were normalised at 12 months compared to the baseline values. Conclusions: This clinical study is the first report of the use of OOS in patients with advanced pancreatic cancer, and demonstrates that it is able to maintain optimal quality of life with reduced severity of toxicity during and after combination treatment with gemcitabine-based chemotherapy.

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint:A Retrospective Analysis

Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Effectiveness of a theory-based tailored mHealth physical activity intervention for women undergoing chemotherapy for breast cancer:A quasi-experimental study

Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021.According to the admission order,30 patients werefirst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efficacy theory,and the theory of planned behavior.The app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social interaction.Patients in the intervention group received three months of personalized online PA guidance in addition to routine care.The control group received routine care.Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast cancer.Results:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed significant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had significant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced significant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has demonstrated a positive impact on promoting PA behavior change and emotional management among breast cancer patients.The‘Breast Care’app integrated various practical behavior change strategies,offering valuable guidance for personalized remote rehabilitation support for cancer patients.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer Hospital.The patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during NCT.The pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major LARS.Conclusions:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable toxicity.With fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

Ganoboninketal C from Ganoderma boninense improves the efficacy of CDDP-based chemotherapy through inhibiting translesion DNA synthesis

Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer agent.Unfortunately,few suitable natural TLS inhibitors have been reported.Here,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as mutagenesis.Moreover,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure.Interestingly,26-3 can also sensitize tumor cells to Gefitinib therapy.Mechanistically,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS pathway.Furthermore,we found that activating transcription factor 3 is a potential novel TLS modulator.Taken together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.