Impact of postoperative lymph node status on the prognosis of esophageal squamous cell carcinoma after esophagectomy following neoadjuvant chemoradiotherapy: a retrospective study

BackgroundNeoadjuvant chemoradiotherapy (nCRT) and surgery are widely used treatments for locally advanced esophageal squamous cell carcinoma (ESCC). Thus, it is critically important to investigate risk factors that affect patient prognosis after preoperative chemoradiotherapy and surgery.MethodsWe conducted a retrospective analysis of 77 patients with ESCC who received nCRT and underwent surgery at our center from January 2015 to December 2019. We analyzed the primary clinical data, postoperative pathological results, recurrence, and death results.ResultsAmong the 77 ESCC patients who received nCRT and surgery, 19 achieved a postoperative pathologic complete response (pCR), and the overall pCR rate was 24.68%. The univariate analysis indicated that postoperative post-neoadjuvant treatment N stage (ypN) metastasis [hazards ratio (HR): 2.908; 95% confidence interval (CI): 0.874–9.676; P=0.082], a high lymph-node ratio [(LNR) >0.1] (HR: 7.149, 95% CI: 1.740–29.369; P=0.006), post-neoadjuvant treatment T3-4 (ypT3–4) (HR: 3.626, 95% CI: 0.824–15.956; P=0.088) affected disease-specific survival (DSS). The multivariate analysis indicated that a high LNR (>0.1) (HR: 6.170; 95% CI: 1.472–25.856; P=0.013) was a significant independent predictor of DSS. The univariate analysis indicated that postoperative ypN metastasis (HR: 2.283; 95% CI: 1.047–4.979; P=0.038) and a high LNR (>0.1) (HR: 4.210; 95% CI: 1.547–11.458; P=0.005) were associated with recurrence-free survival (RFS). The multivariate survival analysis showed that a high LNR (>0.1) (HR: 4.289; 95% CI: 1.538–11.965; P=0.005) was also a significant independent predictor of RFS. In this study, 57 positive lymph nodes were found in 30 of the 77 patients, including 16 left gastric lymph nodes, 9 pericardial lymph nodes, and 7 left supraclavicular lymph nodes.ConclusionsA high LNR (>0.1) in ESCC patients after nCRT is a risk factor of DSS and RFS. ypN metastasis is also an independent predictor of RFS. Left gastric-arterial lymph nodes, para-cardiac lymph nodes, and left supraclavicular lymph nodes are the most common sites of metastasis in ESCC after nCRT.     

Comparison of treatment outcomes of surgery and radiotherapy,including concurrent chemoradiotherapy for stage Ib2-IIb cervical adenocarcinoma patients: a retrospective study

ObjectiveThe study compared the treatment outcomes of surgery versus radiotherapy, including concurrent chemoradiotherapy, in stage Ib2–IIb cervical adenocarcinoma patients in Japan.MethodsOf 57,470 patients diagnosed with stage I–IV cervical cancer from January 2001–December 2011, 1,932 patients with stage Ib2–IIb cervical adenocarcinoma were initially treated by surgery or radiotherapy. The primary endpoint was 5-year overall survival (OS) in all and 614 propensity score-matched (PSM) patients (307 per group). We compared OS and prognosis factors based on age, primary stage, and treatment arm.ResultsIn Japan, >80% (n=1,573) of stage Ib2–IIb cervical adenocarcinoma patients underwent surgery. The 5-year OS of surgery vs. radiotherapy groups were 82.1% (n=704) vs. 79.7% (n=59) (hazard ratio [HR]=1.494; 95% confidence interval [CI]=0.826–2.702; p=0.181) for stage Ib2, 76.6% (n=239) vs. 66.7% (n=54) (HR=1.679; 95% CI=0.986–2.858; p=0.053) for stage IIa, and 71.1% (n=630) vs. 58.9% (n=246) (HR=1.711; 95% CI=1.341–2.184; p<0.001) for stage IIb. In 614 PSM patients balanced for age and carcinoma stage Ib2–IIb, the 5-year OS of surgery vs. radiation groups was 73.0% (n=307) vs. 65.5% (n=307) (HR=1.394; 95% CI=1.044–1.860; p=0.023).In multivariable analysis, age (HR=1.293; 95% CI=1.045–1.601; p=0.018), treatment arm, radiotherapy (HR=1.556; 95% CI=1.253–1.933; p<0.001), and stage IIb (HR=1.783; 95% CI=1.443–2.203; p=0.018) were independent prognosis factors for 5-year OS in stage Ib2–IIb adenocarcinoma patients.ConclusionAge (>65 years), treatment arm (radiotherapy), and stage IIb significantly affect OS in cervical adenocarcinoma patients. Surgery may be considered for <65-year-old patients with stage IIb adenocarcinoma.     

The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Background The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy.Methods Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction.Results GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (p_interaction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012).Conclusions This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX.Subject terms: Prognostic markers, Predictive markers, Outcomes research, Surgical oncology     

Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study

ObjectiveThe survival benefits of retroperitoneal lymphadenectomy (RLNA) for epithelial ovarian cancer (EOC) remain controversial because clinical behaviors differ among subtypes. The purpose of the present study was to clarify whether RLNA increases the survival rate of advanced high-grade serous carcinoma (HGSC).MethodsThis was a retrospective cohort analysis of 3,227 patients with EOC treated between 1986 and 2017 at 14 institutions. Among them, 335 patients with stage IIB-IV HGSC who underwent optimal cytoreduction (residual tumor of <1 cm) were included. Patients were divided into the RLNA group (n=170) and non-RLNA group (n=165). All pathological slides were assessed based on a central pathological review. Oncologic outcomes were compared between the two groups in the original and weighted cohorts adjusted with the inverse probability of treatment weighting.ResultsThe median observation period was 49.8 (0.5–241.5) months. Overall, 219 (65%) out of 335 patients had recurrence or progression, while 146 (44%) died of the disease. In the original cohort, RLNA was a significant prognostic factor for longer progression-free survival (PFS) (hazard ratio [HR]=0.741; 95% confidence interval [CI]=0.558–0.985) and overall survival (OS) (HR=0.652; 95% CI=0.459–0.927). In the weighted cohort in which all variables were well balanced as standardized differences decreased, RLNA was also a significant prognostic factor for more favorable oncologic outcomes (PFS, adjusted HR=0.742; 95% CI=0.613–0.899) and OS, adjusted HR=0.620; 95% CI=0.488–0.787).ConclusionThe present study demonstrated that RLNA for stage III-IV HGSC with no residual tumor after primary debulking surgery contributed to better oncologic outcomes.     

Comparison of prognostic factors of esophageal cancer between a Chinese cohort and the Surveillance,Epidemiology, and End Results (SEER) database: a retrospective cohort study

BackgroundEsophageal cancer is a highly aggressive, early metastasis gastrointestinal malignancy, with geographic differences in prognosis. It is unknown whether there are differences in the survival in different regions among esophageal cancer patients who underwent the treatments. This study was to explore the influencing factors of esophageal cancer survival in patients from China and the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe retrospective cohort study were conducted with 605 Chinese esophageal cancer patients in the Wuxi People’s Hospital and 2,351 patients from the SEER database. The demographic and clinical data were collected from the two cohort, respectively. The outcome was the death during the follow-up. The follow-up ended on November 30, 2021. The Cox proportional hazards model was used in the univariate and multivariate survival analyses, with hazard ratio (HR) and 95% confidence interval (CI).ResultsIn group one, the following were identified as the prognostic factors: female gender (HR =0.568; 95% CI: 0.398–0.811), T3 and T4 stages (HR =3.312; 95% CI: 2.493–4.401), N2 and N3 stages (HR =3.562; 95% CI: 2.631–4.824), and other subtypes of cancer (HR =0.393; 95% CI: 0.223–0.693). The following prognostic were factors identified in group two: age ≥65 years (HR =1.16; 95% CI: 1.058–1.276), female gender (HR =0.843; 95% CI: 0.752–0.945), T3 and T4 stages (HR =1.523; 95% CI: 1.373–1.690), M1 stage (HR =2.554; 95% CI: 2.303–2.832), treatment with surgery and chemotherapy (HR =0.507; 95% CI: 0.457–0.562), and other subtypes of cancer (HR =1.432; 95% CI: 1.298–1.581).ConclusionsThere may be some differences in prognostic factors between Chinese and American patients with esophageal cancer. It is indicated that different management strategies of esophageal cancer should be considered in different populations to improve the prognosis of patients.     

Impact of incomplete surgery and adjuvant chemotherapy for the intraoperative rupture of capsulated stage I epithelial ovarian cancer: a multi-institutional study with an in-depth subgroup analysis

ObjectiveThe aim of the present study was to examine the effects of incomplete surgery and adjuvant chemotherapy on the prognosis of patients with intraoperative rupture of capsulated stage I epithelial ovarian cancer (OvCa).MethodsA regional retrospective study was conducted between 1986 and 2019. Among 4,730 patients with malignant ovarian tumors, 534 women with International Federation of Gynecology and Obstetrics stage IA and IC1 epithelial OvCa were eligible. Differences in survival outcomes were examined between patients with stage IA and IC1 tumors and the effects of uterine preservation, complete-staging lymphadenectomy, and adjuvant chemotherapy were investigated by an in-depth subgroup analysis. To analyze therapeutic effects, baseline imbalances were adjusted using propensity score (PS).ResultsThe prognosis of patients with stage IC1 tumors was worse than those with stage IA. Surgical spill did not affect the site of recurrence. In the PS-adjusted subgroup analysis, uterine preservation (hazard ratio [HR]=1.669; 95% confidence interval [CI]=1.052–2.744), incomplete-staging lymphadenectomy (HR=1.689; 95% CI=1.211–2.355), and the omission of adjuvant chemotherapy (HR=3.729; 95% CI=2.090–6.653) significantly increased the HR of recurrence for patients with stage IC1 tumors compared to those with stage IA tumors. Adjuvant chemotherapy decreased the impact of rupture with uterine preservation (HR=0.159; 95% CI=0.230–1.168) or incomplete-staging lymphadenectomy (HR=0.987; 95% CI=0.638–1.527).ConclusionThe present results suggest intraoperative rupture of capsulated stage I epithelial OvCa is associated with a poor prognosis. When chemotherapy is given for patients receiving incomplete surgery, there is no longer an increased risk of recurrence observed with the rupture.     

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study

ObjectiveAssociations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined.MethodsThe Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks.ResultsHazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20–49, 20–50, and 17–26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78–0.88; aHR=0.78, 95% CI=0.75–0.83; and aHR=0.90, 95% CI=0.86–0.95 for endometrial, cervical, and ovarian tumors).ConclusionHospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.     

Survival and prognostic factors for postoperative primary appendiceal cancer: a retrospective cohort study based on the Surveillance,Epidemiology, and End Results database

BackgroundThe factors affecting the postoperative survival of patients with primary appendiceal cancer (PAC) have yet to be fully explored. And there are no clear guidelines for adjuvant treatment after appendectomy. Whether chemotherapy can prolong patient survival after appendectomy, is critical in guiding postoperative medications. The majority of studies on appendiceal cancer are single case reports, and they focused on the incidence of appendiceal cancer. The present study aimed to investigate the survival characteristics of patients with primary appendiceal cancer after surgery using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe data of 2,891 cases of primary appendiceal cancer between 2004 to 2015 were obtained from the SEER database and subjected to survival analysis using the Kaplan-Meier method and Cox proportional-hazards model. The annual percentage change (APC) was calculated using the weighted least squares method.ResultsThe overall age-adjusted incidence rate per 100,000 population steadily increased from 0.58 in 2004 to 1.63 in 2015. For patients who received chemotherapy, the median overall survival (OS) was 65 months and the 5-year OS rate was 51.9%, and for patients who did not receive chemotherapy or whose chemotherapy status was unknown, the median OS was not reached and the 5-year OS rate was 78.9%. Age [35< age <69: hazard radio (HR) =2.147; 95% confidence interval (CI): 1.442–3.197, P<0.001; age >69: HR =5.259; 95% CI: 3.485–7.937, P<0.001], race (White race: HR =0.728; 95% CI: 0.590–0.899, P=0.003), histologic type (mucinous neoplasm: HR =0.690; 95% CI: 0.580–0.821, P<0.001; malignant carcinoid: HR =0.657; 95% CI: 0.536–0.806, P<0.001), grade (II: HR =1.794; 95% CI: 1.471–2.187, P<0.001; III: HR =2.905; 95% CI: 2.318–3.640, P<0.001; IV: HR =3.128; 95% CI: 2.159–4.533, P<0.001), and stage (localized: HR =0.236; 95% CI: 0.194–0.287, P<0.001; regional: HR =0.425; 95% CI: 0.362–0.499, P<0.001) were identified as independent predictors of survival. And after adjusting for known factors (age, sex, race, tumor size, marital status, histologic type, grade, stage), chemotherapy (HR =1.220; 95% CI: 1.050–1.417, P=0.009) was revealed to be an independent indicator of poor prognosis.ConclusionsThere was an increasing trend in the incidence of appendiceal cancer in the United States between 2004 and 2015. Chemotherapy was revealed to be an independent indicator of poor prognosis, which provide valuable insight into the therapy of primary appendiceal cancer. Large clinical trials of chemotherapy and targeted therapy for appendiceal cancer are urgently needed.     

Lymph node ratio is a prognostic factor for non-small cell lung cancer

The lymph node ratio (LNR) is defined as the number of pathologically positive LNs divided by the number of LNs examined. Some studies reported that high LNR was significantly associated with poor survival of non-small cell lung cancer (NSCLC). However, other studies could not confirm this result. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies published up to July 2015. Primary outcome was the relationship between LNR and disease-specific survival (DSS) and overall survival (OS). Twelve studies with 25138 NSCLC patients were included in this meta-analysis. Higher LNR was significantly associated with decreased OS (HR = 1.93; 95% CI 1.64 – 2.28; P < 0.00001) and DSS (HR = 1.82; 95% CI 1.55 – 2.14; P < 0.00001). In the subgroup analysis, N1 stage NSCLC patients with higher LNR also showed decreased OS (HR = 1.60; 95% CI 1.25 – 2.28; P = 0.0002) and DSS (HR = 1.82; 95% CI 1.55 – 2.21; P < 0.0001). This meta-analysis indicated that LNR was an independent predictor of survival in patients with NSCLC.     

Prognostic value of complete metabolic response on 18F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer

ObjectiveWe investigated the prognostic value of complete metabolic response (CMR) on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC).MethodsPET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis.ResultsBetween 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048).ConclusionCMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.     

The choice of a neoadjuvant chemotherapy cycle for breast cancer has significance in clinical practice: results from a population-based,real world study

Objective:Neoadjuvant chemotherapy (NAC) is currently used in both early stage and locally advanced breast cancers. The survival benefits of standard vs. non-standard NAC cycles are still unclear. This study aimed to investigate the relationship between NAC cycles and survival based on real world data.Methods:We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery. Patients who received at least 4 NAC cycles were defined as having received standard cycles, while patients who received less than 4 NAC cycles were defined as having received non-standard cycles. Kaplan-Meier curves and Cox proportional hazard models were used to estimate the disease-free survival (DFS) and overall survival (OS).Results:Of the 1,024 included patients, 700 patients received standard NAC cycles and 324 patients received non-standard NAC cycles. The DFS estimates were 87.1% and 81.0% (P = 0.007) and the OS estimates were 90.0% and 82.6% (P = 0.001) in the standard and non-standard groups, respectively. Using multivariate analyses, patients treated with standard NAC cycles showed significant survival benefits in both DFS [hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44–0.88] and OS (HR: 0.54, 95% CI: 0.37–0.79). Using stratified analyses, standard NAC cycles were associated with improved DFS (HR: 0.59, 95% CI: 0.36–0.96) and OS (HR: 0.49, 95% CI: 0.28–0.86) in the HER2 positive group. Similar DFS (HR: 0.50, 95% CI: 0.25–0.98) and OS (HR: 0.45, 95% CI: 0.22–0.91) benefits were shown for the triple negative group.Conclusions:Standard NAC cycles were associated with a significant survival benefit, especially in patients with HER2 positive or triple negative breast cancer.     

Sugar-sweetened beverage,artificially sweetened beverage and sugar intake and colorectal cancer survival

Background The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear.Methods Among 1463 stage I–III CRC patients from the Nurses’ Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars.Results Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87–1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95–1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06–2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26–0.75 and 0.70, 95% CI: 0.55–0.89, respectively).Conclusions Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.Subject terms: Epidemiology, Cancer epidemiology, Colorectal cancer, Nutrition     

Impact of metformin on survival outcome in ovarian cancer: a nationwide population-based cohort study

ObjectiveInvestigation of new drugs (INDs) is a tremendously inefficient process in terms of time and cost. Drug repositioning is another method used to investigate potential new agents in well-known drugs. This study assessed the survival impact of metformin medication on ovarian cancer.MethodsA national sample cohort of the Korean National Health Insurance Service Data was analyzed. Cox proportional hazards regression was used to analyzing hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for underlying diseases and medications as confounding factors for overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 866 eligible patients were included from among 1,025,340 cohort participants. Among them, 101 (11.7%) were metformin users. No difference in OS was observed between non-users and users. No difference in OS was observed according to age and Charlson Comorbidity Index. Long-term metformin use (≥720 days) was associated with better OS (adjusted HR=0.244; 95% CI=0.090–0.664; p=0.006). A multivariate Cox proportional hazards model showed that long-term metformin use was an independent favorable prognostic factor for OS (HR=0.193; 95% CI=0.070–0.528; p=0.001) but not for CSS (HR=0.599; 95% CI=0.178–2.017; p=0.408).ConclusionLong-term metformin use reduced all-cause mortality, but not CSS in ovarian cancer. Whether metformin itself reduces deaths because of ovarian cancer requires further investigation.     

Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer

BackgroundAlthough surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC.MethodsThis was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes.ResultsForty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3–73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22–50%), 20% (95% CI: 11–36%), and 7% (95% CI: 2–20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12–36%), 27% (95% CI: 17–44%), 31% (95% CI: 20–48%), and 33% (95% CI: 22–50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy₁₀ was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18–0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16–0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02–1.63, P=0.04). BED >59.5 Gy₁₀ remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15–0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively.ConclusionsRT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.     

Efficacy and safety of sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a two-center study in China

BackgroundRegorafenib is a standard 2nd-line treatment for patients with advanced hepatocellular carcinoma (HCC), but the efficacy and safety of sequential therapy with sorafenib and regorafenib among advanced HCC patients in China is not clear.MethodsThis was a retrospective, two-center, cohort study of advanced HCC patients who received sequential therapy of sorafenib and regorafenib from October 2018 to April 2020 at 2 Chinese institutions. The patients were converted directly to regorafenib after failing to respond to sorafenib monotherapy. The patients underwent evaluations every 4–6 weeks to determine the efficacy and safety of the treatment according to physiological, laboratory, and radiological results. A radiological evaluation using computed tomography or magnetic resonance imaging scans was conducted. The outcomes included overall survival (OS) and progression-free survival (PFS).ResultsA total of 43 patients received regorafenib as a 2nd-line treatment after sorafenib progression. Of these patients, 26 (60.5%) and 17 (39.5%) were diagnosed with Barcelona Clinic Liver Cancer (BCLC) stages B and C, respectively. The median PFS was 11.0 [95% confidence interval (CI): 5.8–16.2] months, and the median OS was 17.0 (95% CI: 12.8–21.2) months. Conversely, the most common toxicities were hand-foot skin reaction (48.8%), diarrhea (32.6%), and hypertension (14%). The most common grade 3–4 toxicities were hypoalbuminemia (4.7%), anemia (4.7%), and thrombocytopenia (4.7%). Alpha-fetoprotein (AFP) ≥400, alanine transaminase (ALT) ≥60 IU/L, and aspartate aminotransferase (AST) ≥60 IU/L before 2nd-line treatment were associated with PFS in the univariable analyses. The Cox proportional-hazards regression analysis showed that AFP [hazard ratio (HR) =0.225; 95% CI: 0.073–0.688; P=0.009], ALT (HR =0.195; 95% CI: 0.051–0.741; P=0.016), AST (HR =0.209; 95% CI: 0.063–0.697; P=0.011), and presence of extrahepatic metastasis (HR =0.074; 95% CI: 0.009–0.608; P=0.015) before 2nd-line treatment were independently associated with PFS.ConclusionsThe sequential therapy of sorafenib and regorafenib is well-tolerated and effective in advanced HCC patients after sorafenib progression based on our two-center real-world data. Patients with good liver function reserve and a high level of AFP before 2nd-line treatment may benefit from sequential treatment. These results still need further validation.     

Comparison between laparoscopic and abdominal radical hysterectomy for stage IB1 and tumor size <2 cm cervical cancer with visible or invisible tumors: a multicentre retrospective study

ObjectiveTo compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors.MethodsWe retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type.ResultsLRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58–1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65–2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723).ConclusionsAmong patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors.Trial RegistrationInternational Clinical Trials Registry Platform Identifier: CHiCTR180017778     

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study

BackgroundLong-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS).MethodsA retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort.ResultsPatients with aMAP scores ≤63.8, 63.8–67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700–0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697–10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097–6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772–0.870)].ConclusionsThis study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.     

Impact of primary tumor location on outcome of liposarcoma patients,a retrospective cohort study

BackgroundTumor location as a prognostic factor for patients with liposarcoma (LPS) has been studied modestly with varying outcomes. The aim was to establish the impact of tumor location on recurrence and survival of LPS patients.MethodsA retrospective database of patients treated for LPS until December 2017 was used to assess 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS) per tumor location using the Kaplan-Meier method and log-rank test. A multivariable Cox regression analysis was performed to adjust for other prognostic factors.ResultsIn total, 518 patients were identified with a median follow-up of 68 months (interquartile range 31–138). Patients with retroperitoneal/intrathoracic WDLPS or DDLPS (p = 0.014), or testicular WDLPS (p = 0.026) developed a local recurrence more often than patients with other tumor locations. No differences between LPS subtypes and tumor location in the development of metastases (p = 0.600) was observed. Five-year LRFS differed significantly between tumor locations (p < 0.001) as well as 5y-DSS (p < 0.001), but 5y-DMFS did not (p = 0.241), with retroperitoneal/intrathoracic LPS having a worse prognosis. Patients with WDLPS in the extremity, trunk or testicular region did not die of disease, except for the rare occasion of dedifferentiation upon recurrence. After adjustment for other prognostic factors, tumor location was only of prognostic value for DSS (retroperitoneal/intrathoracic vs. extremity: HR 5.08, 95% CI 2.41–10.71, p < 0.001).ConclusionFor all tumor locations, DSS mimicked DMFS except for retroperitoneal/intrathoracic LPS, where DSS mimicked LRFS and where DSS was worse than DMFS. This implies that these patients die of local disease instead of metastatic disease.     

Gastrointestinal stromal tumors of the esophagus: evaluation of a pooled case series regarding clinicopathological features and clinical outcome

Background and Objectives: To elucidate diagnostic criteria, clinicopathological features and clinical outcome in patients with esophageal gastrointestinal stromal tumors (GIST), representing an extremely rare subform of GIST with an estimated incidence of about 0.1 to 0.3 per million people. Patients and methods: Esophageal GIST cases from the Ulmer GIST registry consisting of 1077 cases were pooled with case reports and case series of esophageal GIST extracted from MEDLINE. Data were compared with those from 683 cases with gastric GIST from the Ulmer GIST registry. Results: In comparison to gastric GIST, esophageal GIST (n = 55) occurred significantly more frequent in men (p = 0.035) as well as in patients younger than 60 at diagnosis (p < 0.001). Primary tumor sizes were significantly larger (p < 0.001), thereby resulting more frequently in a high-risk classification (OR = 4.53, CI 95% 2.41-8.52, p < 0.001). The 5-year rates of disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) were 50.9%, 65.3% and 48.3%, respectively. The prognosis of esophageal GIST was less favorable compared with gastric GIST (DSS: p < 0.001, HR = 0.158, 95% CI: 0.087-0.288; DFS: p = 0.023, HR 0.466, 95% CI: 0.241-0.901; OS p = 0.003, HR = 0.481, 95% CI: 0.294-0.785; univariate Cox model) after a median follow-up time of 28 months (range 1.9 to 202). Mutational analysis for KIT showed more frequently wild-type status in esophageal GIST (OR = 10.13, CI 95% 3.02-33.96, p < 0.001). Conclusions: Esophageal GIST differ significantly from gastric GIST in respect to clinicopathological features and clinical outcome. To optimize treatment options further prospective data on patients with esophageal GIST are urgently warranted.     

Statin use and breast cancer survival and risk: a systematic review and meta-analysis

The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54–0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53–0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43–0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48–1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.