The use of granulocyte colony stimulating factor (G-CSF) and management of chemotherapy delivery during adjuvant treatment for early-stage breast cancer—Further observations from the IMPACT solid study

ObjectiveTo investigate the use and impact of granulocyte colony-stimulating factors (G-CSF) on chemotherapy delivery and neutropenia management in breast cancer in a clinical practice setting.MethodsIMPACT Solid was an international, prospective observational study in patients with a physician-assessed febrile neutropenia (FN) risk of ≥20%. This analysis focused on stages I–III breast cancer patients who received a standard chemotherapy regimen for which the FN risk was published. Chemotherapy delivery and neutropenia-related outcomes were reported according to the FN risk of the regimen and intent of G-CSF use.Results690 patients received a standard chemotherapy regimen; 483 received the textbook dose/schedule with a majority of these regimens (84%) having a FN risk ≥10%. Patients receiving a regimen with a FN risk ≥10% were younger with better performance status than those receiving a regimen with a FN risk <10%. Patients who received higher-risk regimens were more likely to receive G-CSF primary prophylaxis (48% vs 22%), complete their planned chemotherapy (97% vs 88%) and achieve relative dose intensity ≥85% (93% vs 86%) than those receiving lower-risk regimens. Most first FN events (56%) occurred in cycles not supported with G-CSF primary prophylaxis.ConclusionPhysicians generally recommend standard adjuvant chemotherapy regimens and were more likely to follow G-CSF guidelines for younger, good performance status patients in the curative setting, and often modify standard regimens in more compromised patients. However, G-CSF support is not optimal, indicated by G-CSF primary prophylaxis use in <50% of high-risk patients and observation of FN without G-CSF support.     

Evaluation of a serum 17-hydroxyprogesterone as a predictor of semen parameter improvement in men undergoing medical treatment for infertility

IntroductionThe goal of medical therapy for infertile men with testosterone deficiency (TD) is to improve intratesticular testosterone (ITT). There is a gap in knowledge to identify those who will respond with semen parameter(s) improvement. We hypothesized that serum 17-hydroxyprogesterone (17-OHP) — a marker of ITT — can be used to predict improvement of semen parameter(s).MethodsBetween July 2018 and January 2020, we conducted a prospective study of 31 men with primary infertility, TD, and secondary hypogonadism receiving clomiphene citrate (CC) and/or human chorionic gonadotropin (hCG) for three months. We assessed baseline and followup hormones, including testosterone, 17-OHP, semen parameter(s), and demographics. Semen quality upgrading was based on assisted reproduction eligibility: in-vitro fertilization (<5 million), intrauterine insemination (IUI) (5–9 million), and natural pregnancy (>9 million). Variables were compared using the Mann-Whitney U or Wilcoxon rank test.ResultsTwenty-one men received CC and 10 received CC/hCG. Median followup was 3.7 (3.3–5.1) months. Sixteen men upgraded semen quality. Six of 10 men with baseline total motile sperm count (TMSC) of 0 had motile sperm after treatment, and 11/20 men with TMSC <5 upgraded semen quality into TMSC >5 range. Low 17-OHP was the only factor that predicted semen quality upgrading. Men with 17-OHP ≤55 ng/dL upgraded semen quality and improved hormones, whereas men with 17-OHP >55 ng/dL did not upgrade semen quality.ConclusionsMedical therapy for infertile men with TD resulted in the improvement of sperm concentration, TMSC, testosterone, and 17-OHP. Semen quality upgrading appears to be more significant in patients with low 17-OHP, suggesting that ITT can be used as a biomarker to predict semen parameter(s) improvement.     

Evaluating the utility of computed tomography of the chest for gastric cancer staging

BackgroundInternational guidelines recommend routine computed tomography (CT) of the chest for gastric cancer staging. In Asian countries, where the incidence of pulmonary metastases is less than 1%, some guidelines recommend chest CT only for gastroesophageal junction cancers. If the incidence of pulmonary metastases is also low in Canada, routine chest CT may not be beneficial.MethodsWe performed a retrospective review of patients in northern Alberta with newly diagnosed gastric cancer from January 2010 to July 2016. The primary aim of the study was to determine the incidence of pulmonary metastases at the time of diagnosis in this population. A secondary aim was to identify potential predictors of pulmonary metastases. We reviewed CT reports for pulmonary metastases. Imaging data also included liver metastases, abdominal lymphadenopathy (> 1 cm), ascites and omental or peritoneal nodules. Other data recorded were age, sex, primary tumour location, histologic type and tumour grade.ResultsFour hundred and sixty-two patients (311 men, 151 women) were included in the analysis. Pulmonary metastases were identified in 25 patients (5.4%) overall and in 11 of 299 patients (3.7%) whose primary cancer was not in the cardia. On univariate analysis the presence of liver metastases (odds ratio [OR] 7.72, 95% confidence interval [CI] 3.24–18.37, p < 0.001) and abdominal lymphadenopathy (OR 3.30, 95% CI 1.29–8.48, p = 0.01) was associated with an increased risk of pulmonary metastases. Liver metastases retained statistical significance on multivariate analysis (OR 6.17, 95% CI 2.53–15.03, p < 0.001).ConclusionThe incidence of pulmonary metastases at the time of gastric cancer diagnosis is higher in northern Alberta than previously reported in Asian studies. Abdominal lymphadenopathy and liver metastases confer an elevated risk of pulmonary metastases.     

Adjuvant Chemotherapy for Low-Clinical-Risk Breast Cancer Defined by Modified Version of Adjuvant! Online: A Propensity Score Matched SEER Analysis

BackgroundThe purpose of this research was to investigate whether the modified version of Adjuvant! Online was able to omit chemotherapy (CT) for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and axillary node-negative breast cancer, who are defined as low clinical risk.MethodsFrom 2010 to 2014, HR-positive, HER2-negative, and node-negative breast cancer patients aged 50 years and older were retrieved from the Surveillance, Epidemiology, and End Results (SEER) 18 database. The propensity score matching method was applied between the no-CT and CT groups. Overall survival (OS) was evaluated using Kaplan-Meier analysis and compared across groups using a log-rank test.ResultsA total of 48,857 patients were enrolled. After propensity score matching, the numbers of patients in the no-CT and CT groups were both 3,102. The median follow-up period was 37 months. The 5-year OS rates in the no-CT and CT groups were 92 and 91%, respectively (p = 0.066). In the subgroup with a tumor score (tumor size added to tumor grade) of 2–3, OS was significantly higher in the no-CT group than in the CT group (93 vs. 90%, p < 0.001). In the subgroup with a tumor score of 4, OS was not different between these 2 groups (92 vs. 93%, p = 0.47).ConclusionThis retrospective study provides evidence that CT may not be beneficial to patients 50 years of age or older with HR-positive, HER2-negative, axillary node-negative breast cancer and additionally defined as low clinical risk by a modified version of Adjuvant! Online.     

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

BackgroundInvasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis.MethodsWe evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson''s χ² test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS).ResultsOverall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2− subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2− subtype (OS, hazard ratio: 1.501, 95% CI 1.270–1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281–1.825, p < 0.001), lower histological grade (I–II) (OS, hazard ratio: 1.411, 95% CI 1.184–1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235–1.791, p < 0.001), or tumor burden, such as T_0–2 (OS, hazard ratio: 1.693, 95% CI 1.368–2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405–2.205, p < 0.001) and N_1–2 (OS, hazard ratio: 1.451, 95% CI 1.171–1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187–1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T_3–4 and N₃), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients.ConclusionPatients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.     

Impact of early hypothalamic-pituitary-gonadal axis maturation on prostate cancer: cross-sectional analysis of a Veterans affairs cohort

BackgroundIt has been hypothesized that earlier onset of puberty, and thus a more prolonged exposure to high androgen levels, increases risk of prostate cancer development. Our objective was to determine whether earlier age of first shave and height, as surrogates of pubertal onset, were associated with risk of prostate cancer diagnosis.MethodsA prospectively collected outcomes registry of patients presenting for a prostate biopsy at the Charlie Norwood Veterans Affair Medical Center in Augusta, GA between July 1995 and June 2016 was utilized. The associations between age of first shave and height, each, and risks of a positive prostate biopsy, high grade cancer, and high volume disease were evaluated using univariable and multivariable logistic regression analysis, controlling for baseline patient demographic and oncologic characteristics.ResultsOur cohort included 2,456 patients. Biopsies were positive in 1,257 (51.2%) patients, of whom 293 (23.3%) and 407 (32.4%) had high grade and volume disease, respectively. Median age of first shave was 17.0 years (interquartile range 16.0–19.0) and height was 177.7 cm (172.8–182.9). On multivariable analysis, later of age of first shave was significantly associated with increased odds of a positive prostate biopsy (odds ratio for >18 versus <16 years: 5.34, P=0.02) and taller patients had significantly increased odds of high grade cancer (odds ratio for 175–180 versus <175 cm: 7.46, P=0.037).ConclusionsAmongst patients presenting for a prostate biopsy, those with a later age of first shave and taller height have an increased risk of a positive prostate biopsy and high grade prostate cancer, respectively.     

Conditional Disease-Free and Overall Survival of 1,858 Young Women with Non-Metastatic Breast Cancer and with Participation in a Post-Therapeutic Rehab Programme according to Clinical Subtypes

BackgroundBreast cancer in young women is associated with unfavourable tumour biology and is the main cause of death in this group. Conditional survival analysis estimates survival rates under the pre-condition of already having survived a certain time.ObjectivesTo describe conditional disease-free and overall survival of female breast cancer patients according to clinical subtypes and age.MethodsThis study analyses information from 1,858 breast cancer patients aged between 21 and 54 years, who were taking part in a post-therapeutic rehab programme (time between diagnosis and rehab start: maximum 24, median 11 months). Mean follow-up time was 3.6 years. We describe biological, clinical and pathological features in regard to different age groups (<40 and ≥40 years) and report conditional 5-year survival rates for overall and disease-free survival, and Cox proportional hazard models.ResultsVery young and young patients differed in regard to hormone receptor negativity, tumour grade, lymphovascular invasion, and molecular subtypes. Young women bore triple-negative and HER2-like disease more frequently. Conditional 5-year overall survival did not differ substantially between women <40 and 40–54 years of age (95 vs. 96%). It was highest for women with cancer of the luminal A subtype (98%) and lowest for the triple-negative subtype (91%). Lymphangiosis was a significant predictor of death. Results for disease-free survival were comparable.ConclusionsConditional 5-year overall survival after non-metastatic breast cancer was as high as 95.5%, and disease-free survival was 85.2%. When controlling for time between diagnosis and rehab start, molecular subtypes influenced overall and disease-free survival prospects. When additionally controlling for clinical characteristics, this effect only remained stable for disease-free survival.     

A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia

BackgroundPrimary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted.MethodsEBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective.Results458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = −6.7%, 95%CI = −13.5%–0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p < 0.001). Non-FN treatment-related hospitalisation occurred in 40/228 (17.5%) of ciprofloxacin patients vs 28/230 (12.2%) of G-CSF patients (p = 0.12). There were no differences in other secondary outcomes. G-CSF was associated with an incremental cost-effectiveness ratio of C$1,760,796 per one quality-adjusted life year gained.ConclusionThe primary endpoint of superiority of G-CSF over ciprofloxacin was not demonstrated. While there were reduced FN rates with G-CSF, there were no differences in chemotherapy dose delays/reductions or discontinuations. With the commonly used willingness to pay value of C$50,000/QALY, G-CSF use was not cost-effective compared to ciprofloxacin and deserves scrutiny from the payer perspective.     

The Usefulness of the Pretreatment Neutrophil/Lymphocyte Ratio as a Predictor of the 5-Year Survival in Stage 1–3 Triple Negative Breast Cancer Patients

BackgroundWe have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC).MethodsPatients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS).ResultsThe average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low) and nodal status (positive vs. negative) resulted in four groups with significantly different OS and DFS (log rank p < 0.0001). Significant improvements in OS (p < 0.001) and DFS (p < 0.001) were observed for patients who received chemotherapy and had high NLR but not for patients with low NLR (p = 0.65 and p = 0.07, respectively).ConclusionHigh pretreatment NLR is an independent predictor of poor OS and DFS among TNBC patients. Combining NLR and pN provides better risk stratification for TNBC patients. Chemotherapy appears to be beneficial only in patients with high NLR. Larger prospective studies are needed to validate these findings.     

No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

IntroductionSince the beginning of the HIV epidemic in resource‐rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS‐defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV‐RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk.MethodsWe estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time‐updated CD4 counts, HIV‐RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV‐RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL).ResultsThere were 373 recurrences of PjP during 74,295 person‐years (py) in 10,476 patients. The PjP incidence in the different plasma HIV‐RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV‐RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7).ConclusionsHIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation.     

Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients

BackgroundThe addition of trastuzumab to standard chemotherapy has improved survival in patients with HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings. In higher tumor stages, the addition of pertuzumab is now a standard of care and associated with a favorable toxicity profile. We evaluated the safety and efficacy of the trastuzumab biosimilar SB3 in combination with pertuzumab in HER2-positive breast cancer patients.MethodsSeventy-eight patients with HER2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz were included. Summary measures are reported as medians (25th to 75th percentile) for continuous variables and as absolute frequencies (%) for count data.ResultsThirty-five patients received a median of 4 (3–7) cycles of trastuzumab biosimilar SB3 plus pertuzumab. All patients had a normal baseline left ventricular ejection fraction (LVEF; >50%) prior to the initiation of SB3 plus pertuzumab treatment with a median LVEF of 60% (60–65). Twenty-one patients had a median absolute LVEF decline of 1% (−5 to 0). Two patients (5.7%) had a LVEF reduction ≤50%, but none ≥10%. There were no unexpected adverse events. Twenty-two of 35 patients (63%) were treated with trastuzumab biosimilar SB3 and pertuzumab in the neoadjuvant setting and 11 patients (50%) achieved a pathological complete response. The safety and the efficacy in this setting was comparable to the trastuzumab plus pertuzumab combination in neoadjuvantly treated matched samples.ConclusionIn this series of HER2-positive breast cancer patients, the combination of SB3 plus pertuzumab was consistent with the known safety and efficacy profile of trastuzumab and pertuzumab combination.     

Patient Preferences: Results of a German Adaptive Choice-Based Conjoint Analysis (Market Research Study Sponsored by Eli Lilly and Company) in Patients on Palliative Treatment for Advanced Breast Cancer

IntroductionIntegration of patient preferences into shared decision making improves disease-related outcomes, but such data from patients with advanced breast cancer (aBC) are limited. The objective of this study was to demonstrate the relative importance of overall survival (OS) and progression-free survival (PFS) in relation to quality of life (QoL) and therapy-associated side effects from the perspective of patients with aBC.MethodsPostmenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative aBC receiving first- or second-line treatment were recruited throughout Germany. Patient-relevant attributes for aBC therapy assessment were collected using a stepwise multimodal approach. A conjoint matrix was developed, resulting in 2 attributes for therapy goals (OS and PFS), 4 for QoL, and 6 for side effects. An online quantitative survey was then performed using adaptive choice-based conjoint (ACBC) methodology.ResultsThe quantitative survey included 104 patients: 67 (64.4%) receiving first-line treatment and 37 (35.6%) receiving second-line treatment. The QoL attribute “physical agility and mobility” received the highest utility score (19.4 of 100%), reflecting the greatest importance to patients, followed by treatment goals (OS [15.2%] and PFS [14.4%]). Therapy-related side effects were less important, with nausea/vomiting being the most important (9.3%), followed by infection (6.4%) and hair loss (5.0%). The McFadden pseudo R² (0.805), the root likelihood (0.864), and the χ² test (2,809.041; p < 0.0001) indicated a very good fit of the statistical model.ConclusionUsing ACBC analysis, it appears that QoL, OS, and PFS are most important to postmenopausal patients with aBC in relation to cancer treatment. Side effects seem to be less important if OS or PFS are prolonged and the QoL is maintained. Thus, QoL, OS, and PFS should be considered equally when making treatment decisions in aBC.     

Predictive model containing PI-RADS v2 score for postoperative seminal vesicle invasion among prostate cancer patients

BackgroundSeminal vesicle invasion (SVI) is considered to be one of most adverse prognostic findings in prostate cancer, affecting the biochemical progression-free survival and disease-specific survival. Multiparametric magnetic resonance imaging (mpMRI) has shown excellent specificity in diagnosis of SVI, but with poor sensitivity. The aim of this study is to create a model that includes the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score to predict postoperative SVI in patients without SVI on preoperative mpMRI.MethodsA total of 262 prostate cancer patients without SVI on preoperative mpMRI who underwent radical prostatectomy (RP) at our institution from January 2012 to July 2019 were enrolled retrospectively. The prostate-specific antigen levels in all patients were <10 ng/mL. Univariate and multivariate logistic regression analyses were used to assess factors associated with SVI, including the PI-RADS v2 score. A regression coefficient-based model was built for predicting SVI. The receiver operating characteristic curve was used to assess the performance of the model.ResultsSVI was reported on the RP specimens in 30 patients (11.5%). The univariate and multivariate analyses revealed that biopsy Gleason grade group (GGG) and the PI-RADS v2 score were significant independent predictors of SVI (all P<0.05). The area under the curve of the model was 0.746 (P<0.001). The PI-RADS v2 score <4 and Gleason grade <8 yielded only a 1.8% incidence of SVI with a high negative predictive value of 98.2% (95% CI, 93.0–99.6%).ConclusionsThe PI-RADS v2 score <4 in prostate cancer patients with prostate-specific antigen level <10 ng/mL is associated with a very low risk of SVI. A model based on biopsy Gleason grade and PI-RADS v2 score may help to predict SVI and serve as a tool for the urologists to make surgical plans.     

Survival outcomes and adverse events in patients with chronic kidney disease after coronary artery bypass grafting and percutaneous coronary intervention: a meta-analysis of propensity score-matching studies

BackgroundThe present meta-analysis of propensity score-matching studies aimed to compare the long-term survival outcomes and adverse events associated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD).MethodsElectronic databases were searched for studies comparing CABG and PCI in patients with CKD. The search period extended to 13 February 2021. The primary outcome was all-cause mortality, and the secondary endpoints included myocardial infarction, revascularization, and stroke. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to express the pooled effect. Study quality was assessed using the Newcastle–Ottawa scale. The analyses were performed using RevMan 5.3.ResultsThirteen studies involving 18,005 patients were included in the meta-analysis. Long-term mortality risk was significantly lower in the CABG group than in the PCI group (HR: 0.76, 95% CI: 0.70–0.83, p < .001), and similar results were observed in the subgroup analysis of patients undergoing dialysis and for different estimated glomerular filtration rate ranges. The incidence rates of myocardial infarction (OR: 0.25, 95% CI: 0.12–0.54, p < .001) and revascularization (OR: 0.17, 95% CI: 0.08–0.35, p < .001) were lower in the CABG group than in the PCI group, although there were no significant differences in the incidence of stroke between the two groups (OR: 1.24; 95% CI: 0.89–1.73, p > .05). Subgroup analysis among patients on dialysis yielded similar results.ConclusionsOur propensity score matching analysis revealed that, based on long-term follow-up outcomes, CABG remains superior to PCI in patients with CKD.     

Quality of Life Effects of an Oral Fixed Combination of Netupitant and Palonosetron in Chemotherapy-Induced Nausea and Vomiting Prevention: Real-World Evidence in Patients with Breast Cancer Receiving Anthracycline-Cyclophosphamide-Based Chemotherapy

IntroductionIn a prospective non-interventional study involving 2,173 patients, we showed that use of the oral fixed combination of netupitant 300 mg and palonosetron 0.5 mg (NEPA) for prevention of chemotherapy (Ctx)-induced nausea and vomiting has beneficial effects on the quality of life (QoL) of patients with various types of cancers receiving highly or moderately emetogenic Ctx. Here, we report on the effects on QoL, effectiveness, and tolerability of NEPA in patients with breast cancer exposed to anthracycline-cyclophosphamide (AC)-based Ctx.MethodsThis is a post hoc subanalysis of a prospective non-interventional study in 1,197 patients with breast cancer receiving up to 3 cycles of doxorubicin or epirubicin plus cyclophosphamide and NEPA. NEPA administration was per the summary of product characteristics.ResultsIn cycle 1 of Ctx, a large proportion of patients (84%) reported “no impact on daily life” (NIDL) due to vomiting; 53% of patients reported NIDL due to nausea. The complete response rate was 86/88/81% in the acute/delayed/overall phase in cycle 1, and NEPA was well tolerated throughout the study.ConclusionThe real-world beneficial effects of NEPA prophylaxis on QoL were confirmed for patients with breast cancer receiving AC. NEPA was effective with a good safety profile in this patient population in clinical practice.     

Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

IntroductionThe purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS).MethodsIn this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated.ResultsA total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001).ConclusionLate treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.     

Correlations Between a Dedicated Orthopaedic Complications Grading System and Early Adverse Outcomes in Joint Arthroplasty

BackgroundReliable classification of postoperative complications is important for quality improvement efforts. In 2014, The Knee Society proposed a grading system for complications after TKA, but to our knowledge, a relationship between complication grades and surgical outcomes has not yet been established.Questions/purposesWe attempted to determine (1) whether an association exists between complication grade and early adverse outcomes after TKA and THA, and (2) what proportion of the variability in complications could be associated with the classification grade (a metric of potential predictive value of the grading schema).MethodsA total of 210 primary THAs and TKAs in 201 patients performed at one center from January 1, 2011 to December 31, 2011 were reviewed; of those, 188 patients (94%; 197 procedures) had complete 90-day postoperative data and were evaluated retrospectively for postoperative complications. We defined and graded complications according to the classification system proposed by Iorio et al. and The Knee Society. Early adverse outcomes assessed included length of hospital stay and unplanned readmissions or reoperations. A total of 254 complications were documented in 135 patients (137 procedures); 53 patients (60 procedures) had no complications. Bivariate analyses were conducted to identify associations between complication grade and early adverse outcomes and patient variables; analyses considered patient variables including age, sex, status as a state prisoner (yes or no), American Society of Anesthesiologists score, BMI, and procedure (TKA or THA). Multiple regression and logistic regression analyses were conducted to determine the association between complication grade and early adverse outcomes (length of stay [LOS] and unplanned readmission or reoperations) adjusted for confounding patient variables. Alpha was set at 0.05 for two-sided tests.ResultsMaximum complication grade (range, from 0–4) was associated with a longer LOS (for each point increase of maximum grade, LOS increased 0.105 ± 0.024 days, p < 0.001) and more readmissions or reoperations (odds ratio [OR], 3.79; 95% CI, 1.91–7.54; p < 0.001). Total grade (range, 0–22) also was associated with increased LOS (for each point increase of total grade, LOS increased 0.032 ± 0.006 days, p < 0.001) and increased readmissions or reoperations (OR, 1.34; 95% CI, 1.18–1.53; p < 0.001). Total grade could account for 38% of the variation in LOS and readmissions or reoperations (C-statistic = 0.94; 95% CI, 0.90–0.98); whereas maximum complication grade could account for 35% of the variation in LOS and readmissions or reoperations (C-statistic = 0.35; 95% CI, 0.88–0.96). Thus, we found total grade to be a slightly better predictor of LOS and readmissions or reoperations than maximum grade.ConclusionsWe found that the proposed grading system is applicable to TKA and THA in terms of documentation of complication severity and as an indicator of increased LOS and increased unplanned readmissions or reoperation rates. That total complication grade was a better predictor of LOS than maximum grade suggests that multiple complications of a lesser grade can be just as important as a single higher grade complication in terms of effect on outcomes.     

Cause-specific mortality of low and selective intermediate-risk prostate cancer patients with active surveillance or watchful waiting

BackgroundActive surveillance or watchful waiting (AS/WW) is increasingly being used as an alternative strategy to radical prostatectomy or radiation therapy for appropriately selected patients with prostate cancer (PCa). However, the prognosis of low-risk and selective intermediate-risk PCa patients after AS/WW is poorly defined. In this study we reviewed the patients registered in the Surveillance, Epidemiology, and End Results (SEER) Program to establish a competing risk nomogram for the prediction of prostate cancer-specific mortality (PCSM).MethodsThe information of patients undergoing AS/WW in the SEER program from 2004 to 2015 was obtained. All patients were ISUP (International Society of Urological Pathology) grade 1 or 2 PCa and also fulfilled the National Comprehensive Cancer Network’s definition of low-risk PCa [prostate specific antigen (PSA) <10 ng/mL and cT2aN0M0 or less)]. A competing risk nomogram was used to analyze the association of tumor characteristics with PCSM and non-PCSM among the PCa patients with AS/WW. All cases were randomly divided into a training cohort and a validation cohort (1:1). A competing risk nomogram was constructed to predict PCSM in PCa patients with AS/WW. The performance of the PCSM nomogram was evaluated using the concordance index (C-index) and calibration curve.ResultsA total of 30,538 PCa patients were identified as low risk or selective intermediate risk with AS/WW. The 10-year cumulative incidence of death from prostate cancer and death from other cause were 2.8% (95% CI: 2.4–3.1%) and 19.3% (95% CI: 17.8–20.5%), respectively. Variables associated with PCSM included age, marital status, PSA, and ISUP grade. The PCSM nomogram had a good performance in both the training and validation cohorts, with a C-index of 0.744 (95% CI: 0.700–0.781, P<0.001) and 0.738 (95% CI: 0.700–0.777, P<0.001), respectively.ConclusionsOverall, the prognosis was favorable for the low- and selective intermediate-risk PCa patients with AS/WW. The competing risk nomogram yielded a good performance in identifying subgroups of patients with a higher risk of PCSM and potential candidates for AS/WW.     

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.