Concurrent High PD-L1 Expression and CD8+ Immune Cell Infiltration Predict PD-1 Blockade Efficacy in Advanced EGFR-Mutant NSCLC Patients

ObjectivesThe effectiveness of PD-1 blockade therapy in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is limited. We investigated whether patient characteristics, PD-L1 expression, and immune cell (IC) status in the tumor microenvironment (TME) were associated with PD-1 blockade therapy outcomes.Materials and methodsWe retrospectively reviewed patients with advanced EGFR-mutant NSCLC treated with PD-1 blockade (nivolumab or pembrolizumab) between January 2016 and March 2018. The PD-L1 expression tumor proportion score (TPS) and types and distribution of ICs (CD8, PD-1, CD204, tumoral, and stromal) in the TME were analyzed.ResultsAmong 57 EGFR-mutant NSCLC patients treated with PD-1 blockade, 39 patients had sufficient tissues for analyzing the TME. The overall response rate (ORR) of PD-1 blockade was 12.3%. Only tumoral CD8 positive (CD8⁺) IC status was significantly associated with the response (median tumoral CD8⁺ICs: 299/mm² vs. 115/mm², P < .01). Among the 6 patients with concurrent high PD-L1 expression (TPS: ≥ 50%)/high tumoral CD8⁺ ICs (≥ 205/mm²), 5 (83.3%) showed a response and a significantly longer progression-free survival (PFS) (PFS: 9.4M vs. 1.8M, P < .01). In contrast, none of the 7 patients with high PD-L1 expression/low tumoral CD8⁺ICs (<205/mm²) showed a response.ConclusionConcurrent high PD-L1 expression and high tumoral CD8⁺ ICs could predict the response and longer PFS of PD-1 blockade therapy in EGFR-mutant patients.     

Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis

BackgroundThe significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM.Patient and MethodsThe PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed.ResultsThe main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor.ConclusionOur findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.     

Geriatric Early-Stage Triple-Negative Breast Cancer Patients in Low-risk Population: Omitting Chemotherapy Based on Nomogram

BackgroundConsidering old age and comorbidities, the actual benefit of chemotherapy in older patients with early triple-negative breast cancer (TNBC) remains uncertain. We aimed to select appropriate patients who could avoid chemotherapy in this population.MethodsA total of 6482 patients more than 65 years old with T1-2N0-1M0 TNBC in 2010-2015 were extracted from SEER program. Multivariate logistic regression was performed to identify independent factors associated with chemotherapy usage. Survival analysis was performed using Kaplan-Meier plots and log-rank tests. Independent prognostic factors were identified by multivariate Cox analysis. A nomogram predicting breast cancer-specific survival (BCSS) and a risk stratification model were constructed.ResultsA total of 3379 (52.13%) patients received chemotherapy while 3103 (47.87%) did not. Age, married status, grade, T-stage, N-stage, radiation and breast-conserving surgery (BCS) were significantly associated with chemotherapy usage (all P < .05). Chemotherapy significantly improved OS (HR = 0.606, P < .001) and BCSS (HR = 0.763, P = .006) in the entire population. A nomogram was built by incorporating independent risk factors (age, T-stage, N-stage, grade and radiation). Based on the score of the nomogram, the risk stratification model demonstrated that chemotherapy improved OS (P < .001) and BCSS (P < .001) of patients in the high-risk group (score >180), but not in the low-risk group (score ≤75).ConclusionChemotherapy is beneficial for geriatric patients with T1-2N0-1M0 TNBC in this study, and the risk stratification model indicates the feasibility of sparing chemotherapy in low-risk subgroup without sacrificing survival, providing clinicians tools to weigh the risk–benefit of chemotherapy and customize the individualized treatment accordingly.     

Comorbidities,timing of treatments,and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study

IntroductionFor stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established.Materials and methodsWe analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use.ResultsOverall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P < 0.001). Chemotherapy timing did not vary (P = 0.250) between high and low comorbidity cases. Electively-operated cases with low comorbidities received surgery more promptly than high comorbidity cases. Risks of death and relapse were lower for elective cases given surgery after four weeks than cases given surgery within a week. High comorbidities were always independently associated with poorer outcomes. Chemotherapy use increased over time.ConclusionsOur data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation.     

Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma

BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and MethodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.     

Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial

BackgroundHigh body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients.Patients and methodsPatients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses.ResultsOverall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m² was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS.ConclusionsIn our study, obesity with BMI > 30 kg/m² was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.     

Analysis of the Safety and Pregnancy Outcomes of Fertility-sparing Surgery in Ovarian Malignant Sex Cord-stromal Tumours: A Multicentre Retrospective Study

AimsTo assess the difference in survival between fertility-sparing surgery (FSS) and radical surgery and explore pregnancy outcomes after FSS in stage I malignant sex cord-stromal tumours (MSCSTs).Materials and methodsWe carried out a multicentre retrospective cohort study on patients who were diagnosed with MSCSTs and the tumour was confined to one ovary. The patients were divided into FSS and radical surgery groups. Inverse probability of treatment weighting (IPTW) was used to balance variables between the two groups. Kaplan–Meier analysis was used to compare the difference in disease-free survival (DFS). Univariate and multivariate Cox regression analysis was used to find risk factors of DFS. Univariate logistic regression analysis was used to assess risk factors of pregnancy.ResultsIn total, 107 patients were included, of whom 54 (50.5%) women underwent FSS and 53 (49.5%) received radical surgery. After IPTW, a pseudo-population of 208 was determined and all of the covariates were well balanced. After a median follow-up time of 50 months (range 7–156 months), 10 patients experienced recurrence and two died. There was no significant difference in DFS between the two groups, both in unweighted (P = 0.969) or weighted cohorts (P = 0.792). In the weighted cohort, stage IC (P = 0.014), tumour diameter >8 cm (P = 0.003), incomplete staging surgery (P = 0.003) and no adjuvant chemotherapy (P < 0.001) were the four high-risk factors associated with a shorter DFS. Among 14 patients who had pregnancy desire, 11 (78.6%) women conceived successfully; the live birth rate was 76.9%. In univariate analysis, only adjuvant chemotherapy (P = 0.009) was associated with infertility.ConclusionsOn the premise of complete staging surgery, FSS is safe and feasible in early stage MSCSTs with satisfactory reproductive outcomes.     

Decreased Muscle Mass Prior to and Following Chemotherapy Predicts Morbidity in Testicular Cancer Patients Undergoing Post-Chemotherapy Retroperitoneal Lymph Node Dissection

Introduction/BackgroundThe importance of nutritional status before oncologic surgery has been demonstrated in several solid malignancies. Testicular cancer primarily effects young men, and therefore clinicians may not consider sarcopenia as a factor in this population. We therefore sought to determine the impact of decreased muscle mass, measured by psoas muscle diameter, on outcomes in patients undergoing post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) for metastatic germ cell tumors (mGCTs).Materials and MethodsRecords of all patients undergoing PC-RPLND for mGCTs at our institution were reviewed. Muscle mass was assessed by measuring cross-sectional area of the psoas muscle on pre-chemotherapy and pre-operative computerized tomography. Psoas Index (PSI) was calculated by adjusting total psoas area for patient height (cm²/m²). Univariate and multivariate analysis was performed to assess the predictive value of sarcopenia for morbidity and mortality following PC-RPLND.ResultsFrom 2014-2019, 95 patients underwent PC-RPLND, of whom 64 patients had both pre-chemo and pre-operative cross-sectional imaging. Prior to chemotherapy, mean PSI was 7.36 cm²/m², which decreased to 7.06 cm²/m² (P = .041) following chemotherapy. Patients with Stage III disease had a lower mean PSI than patients with Stage I disease (6.84 cm²/m² vs 7.46 cm²/m², P = .047). Patients who suffered post-operative complications had a lower mean PSI (6.39 cm²/m² vs 7.37 cm²/m², P = .020).ConclusionDecreased muscle mass was predictive of morbidity in patients undergoing PC-RPLND. Patients with higher disease burden had lower pre-operative muscle mass. Further assessment of pre-operative nutritional status in this population may reduce morbidity following PC-RPLND.     

Clinical significance of cachexia index in patients with hepatocellular carcinoma after hepatic resection

BackgroundCancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection.MethodsThe study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height)². The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival.ResultsIn multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06).ConclusionsThe CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status.     

Pre-treatment 18F-RGD Uptake may Predict Adverse Events during Apatinib Antiangiogenic Therapy

AimsThe adverse events during antiangiogenic therapy inevitably influence a patient's quality of life. Therefore, biomarkers to identify patients who will experience adverse events would be very valuable in treatment planning.Materials and methodsBetween September 2016 and December 2019, patients scheduled for single-agent apatinib were prospectively enrolled and underwent ¹⁸F-RGD positron emission tomography/computed tomography (PET/CT) pre-treatment. Maximum and mean standard uptake values (SUV_max and SUV_mean) were obtained from thyroid, liver, gastric cardia, gastric body, gastric pylorus and spleen. Statistical methods included the independent sample t-test, Mann-Whitney U-test, receiver operating characteristic curve analysis and chi-squared test.ResultsIn total, 60 patients were initially screened and consented for ¹⁸F-RGD PET/CT scans. The three most frequent adverse events were fatigue (50%), hypertension (36%) and nausea (36%), accounting for 72% in the 50 patients included in the analysis. SUV_max and SUV_mean of thyroid and liver were significantly associated with fatigue, whereas SUV_max and SUV_mean of thyroid and spleen were significantly associated with hypertension and SUV_max and SUV_mean of thyroid and gastric cardia were significantly associated with nausea (all P < 0.05). The most significant predictors of adverse events were ¹⁸F-RGD SUV_max-liver for fatigue (area under the curve [AUC] = 0.682), SUV_max-spleen for hypertension (AUC = 0.688) and SUV_{max-gastric cardia} for nausea (AUC = 0.698). Classified by the cut-off values for SUV_max-liver (4.57), SUV_max-spleen (6.77) and SUV_{max-gastric cardia} (2.10), patients with low RGD SUV_max in liver, spleen and gastric cardia had statistically higher incidence of fatigue (67.9% versus 27.3%, P = 0.002), hypertension (55.6% versus 13.0%, P = 0.004) and nausea (61.1% versus 21.9%, P = 0.006).ConclusionsLow pre-treatment ¹⁸F-RGD uptake in the liver, spleen and gastric cardia were predictive of the adverse events fatigue, hypertension and nausea during apatinib treatment, respectively.     

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis

ObjectivesThis study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.MethodsPubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients.ResultsTwenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38–2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23–0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06–0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11–9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45–0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55–0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent.ConclusionsThe current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.     

BCG Administration after Prior Radiation Treatment for Prostate Cancer

IntroductionProstate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. The underlying mechanism is incompletely understood but is thought to be related to an altered microenvironment promoting tumorigenesis. However, there is a gap in the literature regarding how the effect of BCG varies according to prior radiotherapy in patients with non–muscle invasive bladder cancer (NMIBC). In this context, we sought to evaluate oncologic outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy.MethodsThis is a retrospective cohort study that includes all patients who received intravesical for NMIBC at our institution from 2001 to 2019. Patients were stratified into 3 cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). The outcomes of interest were recurrence at 1-year, progression to muscle-invasive bladder cancer (MIBC), and progression to metastatic disease. Comparisons were also made between cohorts with respect to elapsed time from radiation therapy. Wilcoxon rank-sum test was used for comparing continuous variables, while χ² and Fischer's exact tests were used to examine categorical variables.ResultsIn 199 total patients who underwent BCG for NMIBC, 23 had a prior history of prostate radiotherapy treatment, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at 1 year. There was no difference in the number of induction or maintenance BCG administrations received between the cohorts within the first year. There was no significant difference in recurrence at 1 year between the 3 cohorts (P = .56). There was also no difference in progression to MIBC or progression to metastatic disease with P = .50 and 0.89, respectively.ConclusionThe risk of recurrence after induction BCG treatment for high-grade NMIBC does not vary according to prior radiation treatment for prostate cancer.     

Modified 5-Item Frailty Index Score as Prognostic Marker After Radical Cystectomy in Bladder Cancer

IntroductionA modified 5-item frailty index was recently developed as a predictor of patient comorbidity-based mortality and morbidity. We evaluate the association between preoperative modified 5-item frailty index score and prognosis after radical cystectomy for bladder cancer.Patients and MethodsIn this multicenter retrospective study, we calculated modified 5-item frailty index scores of the 238 patients that underwent radical cystectomy for bladder cancer between March 2009, and March 2018. The patients were classified into high frailty index score (≥ 2) or low frailty index score (≤ 1) groups for comparison of overall and cancer-specific survival between them. To evaluate the prognostic impact of the preoperative frailty index, we also performed Cox proportional regression analyses for overall, and cancer-specific survival.ResultsOf 238 patients, 53 patients were classified into the high frailty index score group and 185 patients into the low frailty index score group. Overall, 70 patients died of bladder cancer (29%), and 21 patients died of other causes (9%). The patients with high frailty index score had significantly lower rate of overall survival than those with low frailty index score (P < .01). On the other hand, there was no significant difference in cancer-specific survival rate between the 2 groups (P = .07). Multivariable Cox proportional hazard analysis revealed that high modified 5-item frailty index score was independently associated with poor overall survival (P = .01), but not with poor cancer-specific survival (P = .15).ConclusionHigh preoperative modified 5-item frailty index score could be a significant independent predictor of poor prognosis after radical cystectomy in patients with bladder cancer.     

Prognostic factor analysis of irreversible electroporation for locally advanced pancreatic cancer – A multi-institutional clinical study in Asia

IntroductionIrreversible electroporation (IRE) is a modality that utilizes high electric voltage to cause cell apoptosis. IRE has been used to treat locally advanced pancreatic cancer (LAPC). However, studies of IRE via surgical approaches for LAPC are limited. This study aims to analyse the outcomes and related prognostic factors of IRE for Asian patients with LAPC.Materials and methodsFrom 2012 to 2017, this prospective trial for using IRE through surgical approaches for LAPC was conducted in 11 medical centres in Asia. All related and treatment outcomes were analysed from a prospective database.ResultsSeventy-four patients were enrolled. Thirty complications occurred in thirteen (17.6%) patients without mortality. The electrode placement direction (anteroposterior vs. craniocaudal, HR = 14.2, p < 0.01) and gastrointestinal invasion (HR = 15.7, p < 0.01) were significant factors for complications. The progression-free survival (PFS) rate in one year, three years, and five years were 69.1%, 48.7%, and 28.8%, and the overall survival (OS) rate in one year, three years, and five years were 97.2%, 53%, and 31.2%. In univariate analysis, the chemotherapy regimen, local tumour recurrence, axial tumour length, tumour volume, and serum carbohydrate antigen 19-9 levels were all significantly associated with PFS and OS. In multivariate analysis, the chemotherapy regimen was the only significant factor associated with PFS and OS. TS-1 (Tegafur, gimeracil, and oteracil) group has superior survival outcome than gemcitabine group.ConclusionThis study showed that combined induction chemotherapy and surgical IRE for LAPC is safe. For well-selected patients, IRE can achieve encouraging survival outcomes.     

Gene network Analysis Defines a Subgroup of Small Cell Lung Cancer patients With Short Survival

BackgroundSmall cell lung cancer (SCLC) is an aggressive tumor, and despite its sensitivity to chemotherapy and radiotherapy, patients usually have a short survival. There are no clinically relevant predictive factors of responses to therapies, and therapeutic options are still limited.Materials and MethodsClinical data and somatic mutations of genes included in the MSK-IMPACT panel were retrieved from cBioPortal for 108 SCLCs and analyzed to identify mutated gene networks. Results were validated in an independent cohort of 54 SCLCs, whose information was also available from cBioPortal.ResultsDifferent networks were observed in tumors of short and long survivors. Degree (K) and betweenness (B) are key features that characterize a gene in its network of related mutations. By comparing their B/K ratio, 2 signatures of mutated genes were identified, describing short (IL-7R, NTRK2, HNF-1A) and long survivors (NBN, PTPN-11, IRS-1, INPP-4A, PIK-3CG, HGF, LATS-2, SMARCA-4, FLT-3, EIF-4A2, SPEN, PAX-5, SH2-D1A, ARID-1A, HOXB-13, ERCC-4, FANCA, FH, FGFR-2, MST-1R, SMAD-4, DDR-2, IGF-1R, PIK-3CB). Patients with at least 1 mutated gene of the short signature had a worse median overall survival of 8 versus 28 months (P < .001). Patients with at least 1 mutated gene of the long signature had a better median overall survival of 39 versus 20 months (P = .004). The value of the short signature was further confirmed in an independent cohort of SCLCs.ConclusionThe networks of mutated genes could help subclassify SCLCs based on their somatic mutations and aid in identifying a subset of tumors with poor prognosis.     

The Cardioprotective Effect of Vitamin D in Breast Cancer Patients Receiving Adjuvant Doxorubicin Based Chemotherapy

PurposeThe primary objective of this study was to investigate the potential protective effect of Vitamin D (Vit D) on DOX induced cardio toxicity (DIC) in early breast cancer patients receiving adjuvant DOX based chemotherapy (AC). The secondary objective was to investigate the anti–inflammatory effect of Vit D by measuring serum IL-6 and its correlation with cardio toxicity.MethodsThis study was carried out on 150 newly diagnosed women with breast cancer who were planned to receive four cycles of adjuvant AC chemotherapy regimen (60 mg/m² DOX and 600 mg/m² cyclophosphamide) every 21 days. Study patients were randomized 1:1 into a control group treated with AC and a Vit D group treated with AC plus 0.5 µg of Vit D (Bon One 0.5 µg) orally once daily during the whole treatment course. The cardio protective effect of Vit D was assessed by measuring serum levels of Lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and anti–inflammatory Interleukin 6 (IL-6) at baseline, and after 4 cycles of AC in all study patients.ResultsVit D supplementation in Vit D group patients was associated with a significant decrease (P < 0.001) in serum levels of LDH, cTnT, and IL-6 compared to the control group .ConclusionThe present work provides a promising clinical evidence to support the cardio protective effects of Vit D against DIC through attenuating the evoked pro-inflammatory cytokines induced by DOX.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

Comparison of the clinical efficacy of a new prognostic stratification for duodenal adenocarcinoma with that of TNM staging: The importance of T status with regard to the prognosis

BackgroundAlthough the current staging system and therapeutic strategy for duodenal adenocarcinoma (DA) focus on the N status, their validity has not been clarified. In this study, we evaluated the prognostic factors of DA and reviewed the current staging system.MethodsWe included 105 patients who underwent surgical resection of DA in our department between September 2006 and October 2020. Patients with localised disease other than an early tumour (pT1a) were classified into the advanced group, and prognostic factors were compared with those for the Union for International Cancer Control (UICC) classification, 8th edition.ResultsThe 5-year overall survival (OS) rate in the advanced group (n = 55) was 73%. Multivariate analysis revealed that pT4 and pN2 statuses were independent prognostic factors for OS. The prognosis was stratified based on the pT4 and pN2 statuses, whereas the survival curves for patients with pStage II (pN0) and pStage IIIA (pN1) DA overlapped on staging according to the UICC classification. The new classification indicated a favourable prognosis for patients classified as pT1-3N1 stage IIIA (5-year OS, 86%), whereas the prognosis of patients with pT4N0-1 DA was similar to those classified as pT1-3N2 stage IIIB. Patients with pT4N2 DA had a similar prognosis (5-year OS, 24%) as those with metastases, and 75% of these patients showed distant metastasis within one year after surgery.ConclusionBoth T and N statuses affect the prognosis of DA. Patients with pT4N2 DA may require intensive adjuvant chemotherapy. (238 words)     

Margetuximab Versus Trastuzumab in Patients With Advanced Breast Cancer: A Cost-effectiveness Analysis

BackgroundIn the international, randomized, open-label, phase III study SOPHIA trial, margetuximab plus chemotherapy showed improved progression-free survival (PFS), and overall survival (OS) compared with trastuzumab plus chemotherapy. This study aimed to investigate whether margetuximab plus chemotherapy is cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer.Materials and MethodsThe clinical data for this model was derived from the SOPHIA trial. Costs and utility were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced breast cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether margetuximab is cost-effective in CD16A-158F allele carriers.ResultsMargetuximab plus chemotherapy provided an incremental 0.04 QALYs with an incremental cost of $66,109.78, compared with the trastuzumab plus chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $1,486,442.35/QALY, which exceeded the willingness to pay (WTP) threshold. While in the CD16A-158F allele carriers subgroup, the ICER decreased to $592,669.73/QALY. The variance of the utility of PFS state, costs of margetuximab, and utility of progressive disease state were the most influential factors in the sensitivity analysis.ConclusionUnder current WTP threshold, margetuximab plus chemotherapy is not cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer. Selecting CD16A-158F allele carriers might be a considerable option to optimize the cost-effectiveness of margetuximab.     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.