Variation in Rates of Post-Mastectomy Radiotherapy Among Women with Early Invasive Breast Cancer in England and Wales: A Population-Based Cohort Study

AimsThis study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation.Materials and methodsThe study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I–IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations.ResultsAmong 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3–77.3%), but varied less for the high-risk (range 77.1–91.6%) and low-risk groups (range 4.1–32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree.ConclusionsRates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.     

Outcome Differences Between Patients With Node-Negative Breast Cancer Classified According to the St. Gallen Risk Categories

PurposeThe purpose of this study was to compare the 2007 St. Gallen risk categories with the outcomes of patients with node-negative breast cancer (NNBC).Patients and MethodsWe retrospectively reviewed the medical records of 1500 women with pathologically T1-T3 NNBC treated at the Clinic Hospital, Valencia University (Spain) from 1982 to 2000. Systemic adjuvant treatment was administered to 89.9% of the patients in the whole sample (37% received only hormonal therapy and 52.9% chemotherapy). The 2007 St. Gallen criteria were used to divide the whole sample into 1201 patients with intermediate risk (with ≥ 1 of the following: pathologic tumor size > 2 cm, grade 2-3, estrogen receptor and progesterone receptor absent, HER2/neu gene overexpressed or amplified, or age < 35 years) and 299 patients with low risk. Of the 1201 patients with intermediate risk, 56% received adjuvant chemotherapy. The intermediate- and low-risk groups were compared for relapse-free survival (RFS) and breast cancer–specific survival (BCSS).ResultsMedian follow-up of the entire sample was 61 months (range, 2-251 months). At 5 years, the overall RFS rate was 86%, and the BCSS rate was 95%. For low-risk patients, the RFS rate was 92%, and the BCSS rate was 98%. For intermediate-risk patients, the RFS rate was 84%, and the BCSS rate was 94%. There was a statistically significant difference between the 2 groups in terms of RFS (P = .006) and BCSS (P = .041) independent of received treatment.ConclusionUsing the St. Gallen risk categories resulted in significantly different outcomes for patients with NNBC. The St. Gallen classification might be a valuable clinical tool when assessing patients with NNBC.     

早期(T1-2N1)三阴型乳腺癌根治术后辅助放疗的疗效评估

目的:评估乳腺癌根治术后放疗(post-mastectomy radiation therapy,PMRT)在早期(T1-2N1)三阴型乳腺癌(triple negative breast cancer,TNBC)患者中的治疗价值.方法:回顾性分析SEER数据库中根治术后早期(pT1-2N1)TNBC患者的临床数据.将...     

Can Quantitative Measures of T790M Allelic Fraction Predict Survival Outcomes in Patients Receiving Osimertinib? Observations From an Early Access Programme

AimsMultiple studies have shown conflicting results on the correlation between the EGFR T790M quantitative level and survival outcomes in osimertinib-treated patients. We sought to validate such correlations using data from an osimertinib early access programme (EAP) providing access for metastatic non-small cell lung cancer patients with limited treatment options.Patients and methodsThis observational, multicentre, retrospective analysis included EAP participants who received osimertinib until disease progression, intolerable toxicities or death. Digital droplet polymerase chain reaction-based quantitative plasma genotyping was carried out upon disease progression and data were analysed to explore the relationships between T790M mutant allele fraction (MAF), T790M copy number, MAF ratio and post-osimertinib overall survival. Real-world treatment outcomes and safety were also evaluated.ResultsData from 156 EAP participants were analysed (median follow-up 37.7 months). The median age was 62 years, 62.2% were women, 79.5% were never-smokers, 60.9% had Eastern Cooperative Oncology Group performance status 0/1. In patients with available plasma data (n = 114), T790M MAF (%) showed no significant relationships with overall survival (hazard ratio 1.02; 95% confidence interval 0.99–1.04) or time to treatment discontinuation (TTD) (hazard ratio 1.01; 95% confidence interval 0.98–1.04). Absolute T790M copy number and T790M to activating EGFR mutation MAF ratio also showed no prognostic value. The investigator-assessed response rate was 42.3% and the disease control rate was 85.5%. The median TTD was 15.8 (95% confidence interval 12.5–18.5) months and the median overall survival was 22.3 (95% confidence interval 18.6–26.1) months.ConclusionT790M MAF did not correlate with TTD or overall survival in this EAP cohort but limitations should not be overlooked. Observed survival outcomes and the toxicity profile were consistent with data from other real-world series.     

Impact of NCI Socioeconomic Index on the Outcomes of Nonmetastatic Breast Cancer Patients: Analysis of SEER Census Tract–Level Socioeconomic Database

PurposeTo assess the impact of National Cancer Institute socioeconomic status (SES) index on breast cancer–specific survival (BCSS) of nonmetastatic breast cancer patients registered within the Surveillance, Epidemiology and End Results (SEER) census tract–level SES database.Patients and MethodsThe census tract–level SES index is a composite score integrating 7 parameters that assess different dimensions of SES. Women with a nonmetastatic breast cancer diagnosis (stage I-III) diagnosed during 2010-2015 and included in the SEER-SES specialized database were included in the current analysis. Multivariate Cox regression analysis was used to assess the impact of SES index on BCSS.ResultsA total of 296,100 women with nonmetastatic breast cancer were included in the current study. The impact of SES index on BCSS was evaluated in the overall cohort of patients through multivariate Cox regression analysis (adjusted for age at diagnosis, race, stage, and breast cancer subtype). Lower SES was associated with worse BCSS (hazard ratio for group 1 [lowest SES group] vs. group 3 [highest SES group]: 1.428; 95% confidence interval, 1.359-1.499; P < .001). Using additional interaction testing within Cox regression models, the impact of SES on BCSS seems to be modified by breast cancer subtype (P for interaction < .001), race (P for interaction = .001), and stage (P for interaction = .015).ConclusionLower SES index is associated with worse BCSS. Further efforts need to be directed to improving breast cancer outcomes among women with socioeconomically vulnerable attributes (poverty, lower education, and unemployment).     

Impact of evidence-based clinical guidelines on the adoption of postmastectomy radiation in older women

BACKGROUND:

Although postmastectomy radiation therapy (PMRT) improves survival for patients with high‐risk breast cancer, previous literature suggested that it is underused. The impact of recent clinical guidelines on PMRT use is unknown. Accordingly, the authors used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare cohort to determine whether the use of PMRT has increased in response to evidence‐based guidelines.

METHODS:

In total, 38,322 women aged ≥66 years who underwent mastectomy for invasive breast cancer between 1992 and 2005 were identified. Time trends in the receipt of PMRT for low‐risk (T1/T2 N0), intermediate‐risk (T1/T2 N1), and high‐risk (T3/T4 and/or N2/N3) patients were characterized. Multivariate logistic regression identified risk factors for PMRT omission.

RESULTS:

The receipt of PMRT by patients with high‐risk breast cancer increased from 36.5% (95% confidence interval, 26%‐46.9%) to 57.7% (95% confidence interval, 46.9%‐68.4%) between 1996 and 1998 with the publication of landmark clinical trials. However no further increase in PMRT use was observed between 1999 and 2005 despite publication of multiple guidelines endorsing its use; during this period, only 54.8% (2729 of 4978) of high‐risk patients received PMRT. Within this high‐risk group, patients with smaller tumors or less advanced lymph node disease were at risk for PMRT omission.

CONCLUSIONS:

After an initial increase in PMRT use in response to clinical trials, the use of PMRT did not increase further in response to guideline publication, and nearly 50% of patients with high‐risk breast cancer still do not receive PMRT. Additional research is needed to determine how clinical guidelines can be used to bridge the gap between level I evidence and clinical practice. Cancer 2011;. © 2011 American Cancer Society     

Effect of Breast Conservation Therapy vs Mastectomy on Overall Survival and Breast Cancer-Specific Survival Among Men With Stage I-II Breast Cancer: Analysis of SEER, 2000-2018

BackgroundMale breast cancer is a rare malignant tumor, and outcomes of breast conservation therapy (BCT) are currently lacking.MethodThe retrospective, population-based cohort study included 1369 stage I-II (T1–2 N0–1 M0) male breast cancer patients from the SEER database (2000-2018). The patients were grouped in two groups: BCT group and mastectomy group, according to surgical and radiation therapy. Kaplan-Meier method and univariable Cox proportional hazard analysis were used to compare overall survival (OS) and breast cancer-specific survival (BCSS) between two treatment groups. Propensity score matching (PSM) was performed to balance the confounding factors.ResultsOf the 1369 men, 97 (7%) patients received BCT, 1272 (93%) received mastectomy alone. The 5- and 10-year OS rates were 92.3% and 80.7% for BCT group compared with 80.4% and 61.4% for mastectomy group. The 5- and 10-year BCSS rates were 96.5% and 93.9% for patients undergoing BCT, as compared with 93.1% and 84.4% for patients undergoing mastectomy. Compared with mastectomy group, BCT group showed improved OS (hazard ratio [HR], 0.294; 95% CI 0.138-0.623, P = .002) and BCSS (hazard ratio [HR], 0.182; 95% CI 0.040-0.820, P = .027). Of the 791 patients with T1 stage, BCT showed insignificant association with OS (hazard ratio [HR], 0.555; 95% CI 0.207-1.488, P = .242) and BCSS (hazard ratio [HR], 1.217; 95% CI 0.171-8.675, P = .844).ConclusionThe results of this cohort study suggest that BCT is at least equivalent to mastectomy in male breast cancer patients. The underlying mechanism of this association needs further research.     

Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies

BackgroundMicrosatellite instable/deficient mismatch repair (MSI/dMMR) metastatic colorectal cancers have been reported to have a poor prognosis. Frequent co-occurrence of MSI/dMMR and BRAF^V600E complicates the association.Patients and methodsPatients with resected stage III colon cancer (CC) from seven adjuvant studies with available data for disease recurrence and MMR and BRAF^V600E status were analyzed. The primary end point was survival after recurrence (SAR). Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for age, gender, performance status, T stage, N stage, primary tumor location, grade, KRAS status, and timing of recurrence.ResultsAmong 2630 patients with cancer recurrence (1491 men [56.7%], mean age, 58.5 [19–85] years), multivariable analysis revealed that patients with MSI/dMMR tumors had significantly longer SAR than did patients with microsatellite stable/proficient MMR tumors (MSS/pMMR) (adjusted hazard ratio [aHR], 0.82; 95% CI [confidence interval], 0.69–0.98; P = 0.029). This finding remained when looking at patients treated with standard oxaliplatin-based adjuvant chemotherapy regimens only (aHR, 0.76; 95% CI, 0.58–1.00; P = 0.048). Same trends for SAR were observed when analyzing MSI/dMMR versus MSS/pMMR tumor subgroups lacking BRAF^V600E (aHR, 0.84; P = 0.10) or those harboring BRAF^V600E (aHR, 0.88; P = 0.43), without reaching statistical significance. Furthermore, SAR was significantly shorter in tumors with BRAF^V600E versus those lacking this mutation (aHR, 2.06; 95% CI, 1.73–2.46; P < 0.0001), even in the subgroup of MSI/dMMR tumors (aHR, 2.65; 95% CI, 1.67–4.21; P < 0.0001). Other factors associated with a shorter SAR were as follows: older age, male gender, T4/N2, proximal primary tumor location, poorly differentiated adenocarcinoma, and early recurrence.ConclusionsIn stage III CC patients recurring after adjuvant chemotherapy, and before the era of immunotherapy, the MSI/dMMR phenotype was associated with a better SAR compared with MSS/pMMR. BRAF^V600E mutation was a poor prognostic factor for both MSI/dMMR and MSS/pMMR patients.Trial identification numbersNCT00079274, NCT00265811, NCT00004931, NCT00004931, NCT00026273, NCT00096278, NCT00112918.     

Reproductive Factors and Subtypes of Breast Cancer Defined by Estrogen Receptor,Progesterone Receptor,and Human Epidermal Growth Factor Receptor 2: A Register-Based Study From Korea

BackgroundThe relationship between reproductive breast risk factors and breast cancer survival in patients with different breast cancer subtypes is not well known.MethodsWe examined a large-sized, retrospective study of 23,882 subjects from the Korean Breast Cancer Registry. The breast cancer subtype was determined by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Information regarding reproductive factors, including breastfeeding, age at first birth (AFB), and parity, was gathered. Multivariate Cox regression analysis was used to estimate the association among breast cancer subtypes, such as luminal A, luminal B, Her-2/neu overexpressing, and triple negative breast cancer (TNBC), and breast cancer survival as dependent variables and adjusting for age and stage.ResultsHigh parity (≥ 5) increased the recurrence risk of luminal A and B breast cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.96-3.97; P = .0055 and HR, 1.12; 95% CI, 0.42-3.02, respectively; P = .0073) in breast cancer–specific survival (BCSS), but 1 to 3 child births decreased the recurrence risk of luminal A breast cancer (HR, 0.56; 95% CI, 0.34-0.91; P = .0055) and luminal B breast cancer (HR, 0.32; 95% CI, 0.17-0.61; P = .0073) in BCSS. Early AFB (< 20 years) increased the recurrence risk of luminal A breast cancers (HR, 1.61; 95% CI, 0.62-4.26; P = .039) in BCSS and of TNBC (HR, 1.31; 95% CI, 0.78-2.21; P = .0006) in overall survival. Her-2/neu overexpressing breast cancer had no correlation with parity and AFB in breast cancer survival.ConclusionsHigh parity (≥ 5) and early AFB (< 20 years) were correlated with worse clinical outcomes in patients with luminal breast cancer, but not with other subtyped breast cancers.     

Survival of women with inflammatory breast cancer: a large population-based study

BackgroundOur group has previously reported that women with inflammatory breast cancer (IBC) continue to have worse outcome compared with those with non-IBC. We undertook this population-based study to see if there have been improvements in survival among women with stage III IBC, over time.Patient and methodsWe searched the Surveillance, Epidemiology and End Results Registry to identify female patients diagnosed with stage III IBC between 1990 and 2010. Patients were divided into four groups according to year of diagnosis: 1990–1995, 1996–2000, 2001–2005, and 2006–2010. Breast cancer-specific survival (BCSS) was estimated using the Kaplan–Meier method and compared across groups using the log-rank test. Cox models were then fit to determine the association of year of diagnosis and BCSS after adjusting for patient and tumor characteristics.ResultsA total of 7679 patients with IBC were identified of whom 1084 patients (14.1%) were diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000, 2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between 2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were 62%, 67%, 72%, and 76% for patients diagnosed between 1990–1995, 1996–2000, 2001–2005, and 2006–2010, respectively (P < 0.0001). In the multivariable analysis, increasing year of diagnosis (modeled as a continuous variable) was associated with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence interval 0.97–0.99, P < 0.0001).ConclusionThere has been a significant improvement in survival of patients diagnosed with IBC over a two-decade time span in this large population-based study. This suggests that therapeutic strategies researched and evolved in the context of non-IBC have also had a positive impact in women with IBC.     

Statin Use During Concurrent Chemoradiotherapy With Improved Survival Outcomes in Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Nationwide Cohort Study

IntroductionTo determine the effect of statin use during concurrent chemoradiotherapy (CCRT) on overall survival and esophageal squamous cell carcinoma (ESCC)-specific survival in patients with ESCC receiving standard CCRT.MethodsIn this propensity score-matching cohort study, we used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to investigate the effects of statin use during the period of CCRT on overall survival and ESCC-specific survival.ResultsStatin use during the period of CCRT was found to be a considerable and independent prognostic factor for overall survival and ESCC-specific survival. The adjusted hazard ratio (aHR) for all-cause mortality in the statin group compared with that of the non-statin group was 0.65 (95% confidence interval: 0.51–0.84, p = 0.0009). The aHR for ESCC-specific mortality in the statin group compared with that of the non-statin group was 0.63 (95% confidence interval: 0.47–0.84, p = 0.0016). The use of hydrophilic statins such as rosuvastatin and pravastatin was associated with the greatest survival benefits. A dose-response relationship was also found, with higher cumulative defined daily doses and higher daily intensity of statin use associated with lower mortality.ConclusionsThis study is the first to reveal that statin use during the period of CCRT for ESCC is associated with improvement in overall survival and ESCC-specific survival. In addition, we found that use of rosuvastatin, pravastatin, and simvastatin was associated with better survival outcomes for patients with ESCC receiving CCRT. Furthermore, we found a dose-response relationship of statin use associated with lower ESCC-specific mortality.     

Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis

AimsDiabetes is associated with adverse cancer outcomes. However, the effect of hyperglycaemia in non-diabetic cancer patients is unclear.Materials and methodsA systematic search of electronic databases identified publications exploring the effect of hyperglycaemia on overall survival, disease-free survival (DFS) or progression-free survival (PFS). Data from studies reporting a hazard ratio and 95% confidence interval and/or a P-value were pooled in a meta-analysis using generic inverse-variance and random effects modelling. Subgroup analyses were conducted based on method of hyperglycaemia measurement (HbA1c, other) and stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the hazard ratio for overall survival.ResultsTwelve studies comprising a total of 9872 patients were included. All studies reported hazard ratios for overall survival. Three studies reported DFS; two reported PFS outcomes. Definitions of hyperglycaemia and cut-offs varied between studies. Hyperglycaemia was associated with worse overall survival (hazard ratio 2.05, 95% confidence interval 1.67–2.51; P < 0.001) and DFS (hazard ratio 1.98, 95% confidence interval 1.20–3.27; P = 0.007), but did not affect PFS (hazard ratio 1.08, 95% confidence interval 0.72–1.62; P = 0.71). The association with worse overall survival was maintained in subgroups based on method of hyperglycaemia measurement (subgroup difference P = 0.46) and stage (P = 0.14). Meta-regression showed a significantly greater magnitude of association between hyperglycaemia and decreased overall survival in studies with higher proportions of women and diabetic patients.ConclusionsHyperglycaemia is associated with adverse overall survival and DFS in patients with cancer. The therapeutic role of glycaemic control in cancer patients warrants further investigation.     

Radiotherapy Can Improve the Disease‐Free Survival Rate in Triple‐Negative Breast Cancer Patients with T1–T2 Disease and One to Three Positive Lymph Nodes After Mastectomy

Purpose.

Several studies have demonstrated poor locoregional control in patients with triple-negative breast cancer (TNBC), compared with other molecular subtypes of breast cancer. We sought to evaluate whether or not postmastectomy radiotherapy (PMRT) improves locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) outcomes in TNBC patients.

Methods and Materials.

Between January 2000 and July 2007, 553 TNBC patients treated with modified radical mastectomy from a single institution were analyzed retrospectively. Patients were categorized into three groups: low risk (stage T1–T2N0), intermediate risk (stage T1–T2N1), and high risk (stage T3–T4 and/or N2–N3). Cox proportional hazards models were used to evaluate the association between PMRT and LRFS and DFS times after adjusting for other clinicopathologic covariates.

Results.

With a median follow-up of 65 months (range, 1–140 months), 51 patients (9.2%) developed locoregional recurrence and 135 patients (24.4%) experienced disease recurrence. On multivariate analysis, PMRT was associated with significantly longer LRFS and DFS times in the entire cohort. In the intermediate-risk group, PMRT was associated with a longer DFS time but not with the LRFS interval. In the high-risk group, PMRT was associated with significantly longer LRFS and DFS times.

Conclusion.

PMRT is associated with longer LRFS and DFS times in high-risk TNBC patients and a longer DFS time in intermediate-risk TNBC patients. Prospective randomized studies are needed to investigate the best locoregional treatment approaches for patients with this molecular subtype of breast cancer.     

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis

AimsAt diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease.Materials and methodsThis retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors.ResultsForty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS.ConclusionsDefinitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.     

Utilization and impact of a postmastectomy radiation boost for invasive breast cancer

PurposeAdditional radiation following postmastectomy radiation (PMRT) has an undefined benefit. We investigate those likely to be selected for a chest wall boost (CWB) and its effect on breast cancer survival (BCS) and overall survival (OS).Methods and materialsA total of 4747 women diagnosed from 2005 to 2009 were treated with PMRT identified from the California Cancer Registry (CCR); 2686 (57%) received a CWB. Univariate and multivariate analyses compared those receiving and not receiving a CWB for BCS and OS.ResultsWith a median follow-up of 43.6 months, patients likely to receive a CWB were stage III (P ≤ .001), grade 3/4 (P = .03), positive nodes (P = .04), HER 2 + (P = .02). CWB was not related to BCS in the univariate (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.82-1.21), multivariate (HR, 1.04; 95% CI, 0.86 -1.26) analyses, and was not related OS for the univariate (HR, 0.92; 95% CI, 0.78-1.10), multivariate (HR, 0.95; 95% CI, 0.80-1.13) analyses. However, in multivariate analysis, patients not receiving chemotherapy who had a CWB had better BCS (HR, 1.77; 95% CI, 1.11-2.83).ConclusionsThe majority of patients were treated with a CWB. We found no difference in BCS or OS with the addition of a CWB.     

Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

AimsProgrammed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender.Materials and methodsA PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women.ResultsIn total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65–0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54–0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66–0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63–0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53–0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58–0.88, P = 0.372).ConclusionThis is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.     

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis

AimsThere is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure.Materials and methodsIndividual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42–54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan–Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases.ResultsSix hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9–7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5–31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1–311.6, P = 0.003).Conclusion4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

Comparing the association between multiple chronic conditions,multimorbidity, frailty,and survival among older patients with cancer

IntroductionThe high prevalence of multiple chronic conditions (MCC), multimorbidity, and frailty may affect treatment and outcomes for older adults with cancer. The goal of this study was to use three conceptually distinct measures of morbidity to examine the association between these measures and mortality.Materials and MethodsUsing Medicare claims data linked with the 2012–2016 Ohio Cancer Incidence Surveillance System we identified older adults with incident primary cancer sites of breast, colorectal, lung, or prostate (n = 29,140). We used claims data to identify their Elixhauser comorbidities, Multimorbidity-Weighted Index (MWI), and Claims Frailty Index (CFI) as measures of MCC, multimorbidity, and frailty, respectively. We used Cox proportional hazard models to examine the association between these measures and survival time since diagnosis.ResultsLung cancer patients had the highest levels of MCC, multimorbidity, and frailty. There was a positive association between all three measures and a greater hazard of death after adjusting for age, sex (colorectal and lung only), and stage. Breast cancer patients with 5+ comorbidities had an adjusted hazard ratio (aHR) of 1.63 (95% confidence interval [CI]: 1.38, 1.93), and those with mild frailty had an aHR of 3.38 (95% CI; 2.12, 5.41). The C statistics for breast cancer were 0.79, 0.78, and 0.79 for the MCC, MWI, and CFI respectively. Similarly, lung cancer patients who were moderately or severely frail had an aHR of 1.82 (95% CI: 1.53, 2.18) while prostate cancer patients had an aHR of 3.39 (95% CI: 2.12, 5.41) and colorectal cancer patients had an aHR of 4.51 (95% CI: 3.23, 6.29). Model performance was nearly identical across the MCC, multimorbidity, and frailty models within cancer type. The models performed best for prostate and breast cancer, and notably worse for lung cancer. The frailty models showed the greatest separation in unadjusted survival curves.DiscussionThe MCC, multimorbidity, and frailty indices performed similarly well in predicting mortality among a large cohort of older cancer patients. However, there were notable differences by cancer type. This work highlights that although model performance is similar, frailty may serve as a clearer indicator in risk stratification of geriatric oncology patients than simple MCCs or multimorbidity.     

T1-2N0M0 Triple-Negative Breast Cancer Treated With Breast-Conserving Therapy Has Better Survival Compared to Mastectomy: A SEER Population-Based Retrospective Analysis

BackgroundFor early-stage breast cancer, the two current mainstay treatments are breast-conserving therapy (BCT; lumpectomy followed by radiotherapy [RT] and BCT) and mastectomy. Generally, triple-negative breast cancer (TNBC) is more aggressive compared to hormone receptor–positive breast cancer. We sought to investigate the effect of BCT compared to mastectomy on overall survival (OS) and breast cancer–specific survival (BCSS) in T1-2N0M0 TNBC.Patients and MethodsA population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into 3 groups according to surgical modality and RT: BCT, mastectomy alone, and mastectomy with RT. The survival end points were OS and BCSS, and survival analysis was performed by the Kaplan-Meier method and the log-rank test among treatment types.ResultsA total of 14,910 female subjects with T1-2N0M0 TNBC diagnosed between 2010 and 2014 were included. A total of 7381 patients had BCT; 6967 had mastectomy alone, and 562 had mastectomy with RT. Patients treated with BCT had better OS (log-rank P < .05) and BCSS (log-rank P < .05) than those receiving mastectomy with or without RT. The 5-year OS was 88.6% for BCT, 83.0% for mastectomy alone, and 79.6% for mastectomy with RT. The 5-year BCSS was 94.3% for BCT, 93.3% for mastectomy alone, and 83.7% for mastectomy with RT.ConclusionIn patients with T1-2N0M0 TNBC, BCT was associated with superior OS and BCSS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT.