Predicting the cancer burden in Catalonia between 2015 and 2025: the challenge of cancer management in the elderly

Background

Developing effective cancer control programmes requires information on the future cancer burden in an ageing population. In our study we predicted the burden of cancer in Catalonia from 2015 to 2025.

Methods

Bayesian age–period–cohort models were used to predict the burden of cancer from 2015 to 2025 using incidence data from the Girona and Tarragona cancer registries and cancer mortality data from the Catalan mortality registry. Using the Bashir–Estève method, we divided the net change in the number of cases between 2015 and 2025 into changes due to population size (S), cancer risk (R) and age (A) distribution.

Results

By 2025, there will be 21,743 new cancer cases in men (40% aged > 74 years) and 17,268 in women (37% aged > 74 years). More than 40% of the new cases will be diagnosed among population aged 74 and older in prostate, colorectal, lung, bladder, pancreatic and stomach cancers in men, and in colorectal, pancreatic and bladder cancers and leukaemia in women. During 2015–2025, the number of new diagnoses will increase by 5.5% in men (A + R + S = 18.1% ? 13.3% + 0.7% = 5.5%) and 11.9% in women (A + R + S = 12.4% ? 1.1% + 0.6% = 11.9%). Overall cancer mortality rates will continue to decrease during 2015–2025. Lung cancer will be the most lethal cancer among men (N = 2705) and women (N = 1174).

Conclusions

The increase in the number of cancer cases in Catalonia from 2015 to 2025 will mostly affect the elderly, prompting the need for increased collaboration between geriatricians and oncologists.

     

Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma harboring <Emphasis Type="Italic">EGFR</Emphasis> mutations

Purpose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma.

Patients and methods

This study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated.

Results

Median PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6–12.8) months for Bev + CP group and 4.7 (95% CI 4.4–5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293).

Conclusions

First-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.

     

A critical prognostic analysis of neutrophil–lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma

Background

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC).

Methods

Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated.

Results

The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3–186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037).

Conclusion

For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

     

Long-term outcomes of endoscopic submucosal dissection versus surgery in early gastric cancer meeting expanded indication including undifferentiated-type tumors: a criteria-based analysis

Background

Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) meeting the expanded indication is considered investigational. We aimed to compare long-term outcomes of ESD and surgery for EGC in the expanded indication based on each criterion.

Methods

This study included 1823 consecutive EGC patients meeting expanded indication conditions and treated at a tertiary referral center: 916 and 907 patients underwent surgery or ESD, respectively. The expanded indication included four discrete criteria: (I) intramucosal differentiated tumor, without ulcers, size >2 cm; (II) intramucosal differentiated tumor, with ulcers, size ≤3 cm; (III) intramucosal undifferentiated tumor, without ulcers, size ≤2 cm; and (IV) submucosal invasion <500 μm (sm1), differentiated tumor, size ≤3 cm. We selected 522 patients in each group by propensity score matching and retrospectively evaluated each group. The primary outcome was overall survival (OS); the secondary outcomes were disease-specific survival (DSS), recurrence-free survival (RFS), and treatment-related complications.

Results

In all patients and subgroups meeting each criterion, OS and DSS were not significantly different between groups (OS and DSS, all patients: p = 0.354 and p = 0.930; criteria I: p = 0.558 and p = 0.688; criterion II: p = 1.000 and p = 1.000; criterion III: p = 0.750 and p = 0.799; and criterion IV: p = 0.599 and p = 0.871). RFS, in all patients and criterion I, was significantly shorter in the ESD group than in the surgery group (p < 0.001 and p < 0.003, respectively). The surgery group showed higher rates of late and severe treatment-related complications than the ESD group.

Conclusions

ESD may be an alternative treatment option to surgery for EGCs meeting expanded indications, including undifferentiated-type tumors.

     

Clinicopathological analysis of UHRF1 expression in medulloblastoma tissues and its regulation on tumor cell proliferation

Studies have showed the involvement of ubiquitin-like with PHD and RING finger domains 1 (UHRF1) in tumorigenesis and progression. This study focused on the relationships between UHRF1 and medulloblastoma (MB). Immunostaining and western blotting demonstrated differential expression of UHRF1 in MB tissues and no UHRF1 expression in normal cerebellum tissues. Univariate survival analysis revealed MB patients with high UHRF1 expression had significantly shorter OS and PFS than patients with low UHRF1 (OS p = 0.009, PFS p = 0.003). Multivariate analysis illustrated that UHRF1 expression level is an independent prognostic factor influencing the OS and PFS (OS p = 0.038, PFS p = 0.014). UHRF1 expression levels were significantly different among molecular subgroups of MB (p = 0.003). Down-regulation of UHRF1 by RNAi inhibited proliferation and clonogenic ability of MB cell lines with cell cycle arrest in G1/G2-phase. Meanwhile, cells transfected with lenti-shUHRF1 showed increased p16 expression and location shift of CDK4 in MB cells. These findings indicate UHRF1 may promote cell proliferation and be a potential biomarker that can be used as a prognostic parameter and a therapeutic target for MB.     

The effect of aspirin on circulating tumor cells in metastatic colorectal and breast cancer patients: a phase II trial study

Purpose

Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial–mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC).

Methods

The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression.

Results

Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p < 0.001) but not MBC (p = 0.0532); besides, ratio of E+ CTCs increased (p = 0.037) and M+ CTCs decreased at 2 months in MCC (p = 0.013), but neither the ratio of E+ or M+ CTCs changes significantly in MBC; vimentin expression of M+ CTCs is higher than E+ and B+ CTCs either in MBC or MCC patients at baseline (p < 0.01); and aspirin suppresses the vimentin expression in M+ (p = 0.002)and B+ (p = 0.006) CTCs of MCC and M+ CTCs of MBC (p = 0.004); besides it find vimentin expression in B+ (p = 0.004) or M+ (p < 0.001), CTCs are markedly decreased in patients with total CTC numbers declined.

Conclusion

Aspirin could decrease CTCs numbers and block EMT transition in MCC patients and part of MBC patients.

     

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice

Introduction

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data.

Materials and methods

Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile.

Results

A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2? patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%).

Conclusions

Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

     

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment

Background

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment.

Methods

Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events.

Results

A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy.

Conclusions

The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

     

Trends in progression-free survival (PFS) and time to progression (TTP) over time within first-line aromatase inhibitors trials in hormone receptor-positive advanced breast cancer

Background

Over the last 20 years, aromatase inhibitors (AI) have been tested in clinical trials as first-line therapy for hormone receptor-positive (HR-positive) advanced breast cancer (ABC), firstly as experimental arms, when they proved to be effective, and recently as control arms. This analysis aims to evaluate trends in progression-free survival (PFS) and time to progression (TTP) over time.

Patients and methods

A literature review was conducted using the MEDLINE database to identify randomized controlled phase II or III trials which reported PFS or TTP of at least one arm using first-line AI HR-positive ABC patients. A linear correlation was used to access the association between the year of the first patient enrolled and the observed PFS/TTP.

Results

The search retrieved 19 trials, accounting for 4552 postmenopausal patients divided into 21 separate AI treatment arms. The PFS/TTP increased from 6 to 9 months in the earlier trials to 13–16 months in the current era, representing an absolute gain of approximately 7 months, without the addition of any other drug. Our analysis showed a positive correlation between the year of the first patient enrolled in these trials and median PFS/TTP reported (R ² = 0.34; p < 0.01). No correlation was found between the year of the first patient included in these trials and other potential prognostic factors such as visceral metastasis at baseline (R ² = 0.26; p = 0.20) or exposure to adjuvant therapy (R ² = 0.05; p = 0.18).

Conclusion

Patients treated with first-line AIs in the more recently conducted trials have longer PFS/TTP when compared to their counterparts treated with the same drugs in older studies. These findings have important implications for the estimation of sample size and follow-up periods for the planning of future trials as well as in the translation of the results into clinical practice decisions.

     

Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657)

Purpose

The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis may contribute to the development of bone metastases (BM). We studied gene expression in this pathway in primary breast cancer (BC) to determine correlations with clinical characteristics and outcomes in the neoadjuvant I-SPY1 study.

Methods

We evaluated RANK/RANKL/OPG expression using expression microarrays in I-SPY1 (n = 149). Associations with clinical features were determined using t test and ANOVA. Associations between biomarker high versus low groups (dichotomized at an optimal cutpoint) and recurrence-free survival (RFS) were evaluated using the log-rank test and in a multivariate Cox proportional hazard model. A pooled external neoadjuvant cohort with gene expression data (GSE25066) (Hatzis et al. in JAMA 305(18):1873–1881, 30) (n = 425) was used for validation. Associations with site-specific relapse were evaluated using the t-test and multivariate logistic regression adjusting for hormone receptor (HR) status.

Results

RANK was significantly higher in HR negative versus HR positive (p = 0.027), in basal versus non-basal disease (p = 0.004), and in those achieving pathologic complete response (p = 0.038); the associations with HR negative and basal BC were also significant in GSE25066. In both datasets, higher RANK associated with significantly worse RFS (I-SPY1: p = 0.045, GSE25066: p = 0.044). However, this association did not remain significant after adjusting for HR status. In I-SPY1 patients with recurrence, higher RANK correlated with BM versus non-BM (p = 0.045), even after adjusting for HR status (p = 0.035).

Conclusions

RANK is increased in HR negative and basal BC, and correlates with worse RFS and risk of BM. The RANK pathway is a potential therapeutic target in BC.

     

Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: a Peruvian experience

Background

Non-Hodgkin lymphoma (NHL) is the most common cancer in people with HIV. Although 95% of HIV patients are in developing countries like Peru, the majority of these studies have been conducted in developed countries. In this study we aim to evaluate prognostic factors associated with outcomes in HIV positive patients undergoing systemic therapy for treatment of NHL.

Methods

This retrospective study includes patients with NHL seen in the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2004 to 2014. Patients were divided into two groups: antiretroviral therapy (ART) -naïve (n?=?34) and those previously treated, ART-exposed (n?=?13), at the time of diagnosis. All patients received chemotherapy and ART. The medical records were reviewed. Data were analyzed using t-test and chi-square test. Survival curves were estimated by the Kaplan-Meier method and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model.

Results

All ART-exposed patients were from the capital city (p?=?0.039); they had significantly lower hemoglobin levels compared to ART-naïve patients (p?=?0.026). The median OS was 47.7 months with a 5-yr OS of 36.1%. The median OS for ART naïve patients was significantly higher than that for ART-exposed patients (57.05 and 21.09 months, respectively; p?=?0.018). Advanced stage and low serum albumin were associated with lower OS in both groups. Age?>?60 was associated with worse outcomes in the ART-naïve cohort.

Conclusions

Advanced stage, low serum albumin and previous ART treatment were the primary prognostic factors associated with poorer outcomes in patients with NHL and HIV infection. In ART-naïve patients, age?>?60 was associated with worse outcomes but in this cohort, older patients still had better overall outcomes than ART-exposed patients.

     

Anthropometric factors,adult weight gain,and mammographic features

Purpose

To evaluate the association between anthropometric factors, weight gain during adulthood, and mammographic features among 1,435 women recruited at screening mammography.

Methods

Spearman’s partial coefficients were used to evaluate the correlation of anthropometric factors with mammographic features (percent density, absolute dense area, and non-dense area). Multivariate generalized linear models were used to evaluate the associations between weight change categories and mammographic features.

Results

Body mass index was inversely correlated with percent density (r = ?0.49, p < 0.0001) or absolute dense area (r = ?0.21, p < 0.0001) and positively correlated with absolute non-dense area (r = 0.69, p < 0.0001). However, body mass index was positively correlated with absolute dense area when adjusting for absolute non-dense area (r = 0.16, p < 0.0001). Similar results were observed for weight, waist circumference, and waist-to-hip ratio with mammographic features. Within increasing categories of weight change, percent density (p _trend < 0.0001) and absolute dense area (p _trend = 0.025) increased, while absolute non-dense area decreased (p _trend < 0.0001). After stratification by the median of non-dense area, the positive association between weight gain and absolute dense area remained only among women with higher non-dense area.

Conclusions

Adiposity seems positively associated with both dense and non-dense areas following adjustment for each other. Our findings suggest a higher breast dense area among women who gained weight and that a minimum of breast fat may be needed to promote the proliferation of this fibroglandular tissue.

     

Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pre-treated with a non-platinum-based regimen in the first-line setting: a randomized phase II study of the Hellenic Oncology Research Group (HORG)

Background

Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.

Patients and methods

A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m² on day 1 and 100 mg/m² on day 8 plus cisplatin 80 mg/m² on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m² plus cisplatin 80 mg/m² on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).

Results

The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).

Conclusions

In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.

ClinicalTrials.gov Identifier

NCT00614965.

     

Metabolic Syndrome Negatively Impacts the Outcome of Localized Renal Cell Carcinoma

The aim of this study was to analyze the impact of metabolic syndrome (MetS) on outcome of patients with localized renal cell carcinoma (RCC). A retrospective database was compiled consisting of 646 patients who underwent surgery for localized RCC between 2005 and 2014. A total of 439 patients were eligible for final analysis. For diagnosis of MetS, the WHO criteria of 1998 were used. Median follow-up was 32 months (ranging from 2 to 119). Kaplan-Meier and log-rank analyses were performed to compare patients with and without MetS or its components. Univariate and multivariate logistic regression identified prognostic factors for progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). In our cohort, 9.8% (n = 43) of patients were diagnosed with MetS. There were no differences between patients with and without MetS regarding clinicopathological parameters with the exception of patients’ age (p = 0.002). Kaplan-Meier and log-rank analyses revealed a shorter PFS for patients with MetS (p = 0.018), whereas no differences were found for each of the single components of MetS, namely, diabetes mellitus (DM) (p = 0.332), BMI >30 kg/m² (p = 0.753), hypertension (p = 0.451), and hypertriglyceridemia (p = 0.891). Logistic regression identified age (HR = 1.92, p = 0.03), tumor stage (HR = 4.37, p < 0.001), grading (HR = 4.57, p < 0.001), nodal status (HR = 3.73, p = 0.04), surgical margin (HR = 1.96, p = 0.04), concomitant sarcomatoid differentiation (HR = 5.06, p < 0.001), and MetS (HR = 1.98, p = 0.04) as independent factors for PFS. For CSS, only age (HR = 2.62, p = 0.035), tumor stage (HR = 3.06, p < 0.02), and grading (HR = 6.83, p < 0.001) were significant. In conclusion, patients with localized RCC and MetS show significantly reduced PFS and might profit from specific consultation and follow-up.     

Gemcitabine versus FOLFIRINOX in patients with advanced pancreatic adenocarcinoma hENT1-positive: everything was not too bad back when everything seemed worse

Purpose

hENT1 is a transmembrane protein which acts as a nucleoside transporter and is the main mediator of Gemcitabine (GEM) uptake into human cells. In this retrospective study we compared GEM versus FOLFIRINOX in patients with metastatic pancreatic cancer in which hENT1 evaluation was available.

Methods

149 patients affected by unresectable metastatic pancreatic cancer, treated in our institution from 2009 to 2013, have been screened for inclusion in this retrospective study. Seventy patients, treated with GEM or FOLFIRINOX in first-line therapy, fulfilled clinical inclusion criteria for survival analysis. Thirty-one patients were available and contained sufficient quality/quantity RNA for evaluation of hENT1 expression by RT-PCR. The primary endpoint was OS and the secondary endpoint was PFS.

Results

The survival analysis, carried out on 70 patients regardless of hENT1 expression, showed a statistically longer OS and PFS in the group treated with FOLFIRINOX compared to GEM. Within the exploratory analysis, which included 31 patients, no differences were found in hENT1 positive patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89; 95 % CI 0.3–2.5; p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, 95 % CI 0.2–2.2; p = 0.61). GEM-treated hENT1 positive patients showed a statistically significant improvement both of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004) in comparison to GEM-treated hENT1 negative patients.

Conclusions

In our exploratory analysis GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1 positive metastatic pancreatic cancer.

     

Tumor-associated macrophages and crown-like structures in adipose tissue in breast cancer

Purpose

We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer.

Methods

Breast adipose tissue was obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast tissue of breast cancer patients (N = 84, Group 2), and breast cancer with adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated.

Results

Group 3 had the largest number of CD68-positive (CD68⁺) and CD163-positive (CD163⁺) macrophages and CLSs within adipose tissue (P < 0.001). Among Group 3, cases with high levels of CD68⁺ and CD163⁺ macrophages commonly had a higher histologic grade (P = 0.016 and P = 0.045), and cases with CD163⁺ CLSs were correlated with old age (P = 0.042), estrogen receptor negativity (P = 0.013), human epidermal growth factor receptor-2 positivity (P = 0.043), and non-luminal A type (P = 0.039). Upon univariate analysis, high levels of CD163⁺ macrophages were associated with shorter disease-free survival in node-negative breast cancer patients (P = 0.033), and CD68⁺ CLSs were associated with shorter overall survival in node-positive breast cancer patients (P = 0.015).

Conclusions

CD68⁺ and/or CD163⁺ tumor-associated macrophage infiltration as well as CLSs are present in adipose tissue nearby the breast cancer lesion, and are associated with various clinicopathologic parameters of breast cancer.

     

Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ

Purpose

Body composition parameters including low muscle mass, muscle attenuation (which reflects muscle quality) and adipose tissue measurements have emerged as prognostic factors in cancer patients. However, knowledge regarding the possibility of excessive muscle loss during specific systemic therapies is unknown. We describe the changes in body composition and muscle attenuation (MA) during taxane- and anthracycline-based regimens and its association with overall survival (OS) in metastatic breast cancer patients.

Methods

The lumbar skeletal muscle index (LSMI) was used as marker of muscle mass. LSMI, MA, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intramuscular adipose tissue (IMAT) were measured before and after first-line treatment with paclitaxel (n = 73) or 5-fluorouracil-doxorubicin-cyclophosphamide (FAC) (n = 25) using CT-images. Determinants of the change of LSMI and MA were analyzed using multiple linear regression. OS was assessed using Cox proportional hazard models.

Results

MA significantly decreased during paclitaxel treatment (? 0.9 HU, p = 0.03). LSMI (p = 0.40), SAT (p = 0.75), VAT (p = 0.84) and IMAT (p = 0.10) remained stable. No significant alterations in body composition parameters during FAC-treatment were observed. Previous (neo-)adjuvant chemotherapy contributed to larger loss of MA during the current treatment. Body composition changes during chemotherapy were not associated with OS.

Conclusions

MA decreased during treatment with paclitaxel, while muscle mass was stable. Body composition changes are not associated with survival in the absence of progressive disease.

     

Effectiveness and safety of aflibercept for metastatic colorectal cancer: retrospective review within an early access program in Spain

Purpose

In the VELOUR study, aflibercept + FOLFIRI regimen resulted in improved survival in metastatic colorectal cancer (mCRC) patients who progressed after oxaliplatin. The use of aflibercept outside the clinical trial framework needs to be further assessed in terms of effectiveness and tolerability.

Methods

Early access to aflibercept through a named patient programme (NPP) was provided to mCRC patients receiving FOLFIRI as second-line treatment in Spain. The effectiveness of aflibercept was assessed as progression-free survival (PFS) achieved within the NPP population. Post hoc analyses on PFS were done according to certain baseline characteristics (K-RAS mutation, prior targeted therapy) or prognostic factors.

Results

Registries from 71 mCRC patients included in the NPP were reviewed retrospectively. The median age for the NPP population was 64 years (19.7 % aged ≥70 years) and 63.4 % patients had ≥2 metastases. A median PFS of 5.3 months (95 % CI, 3.6–8.5 months) was achieved, which did not depend on K-RAS mutation status or prior targeted therapy received. The risk of progression or death increased in patients with a poor prognosis as per the GERCOR score (performance status [PS] 1–2 and increased baseline lactate dehydrogenase [LDH] level) compared with patients with a good prognosis (PS 0 and normal LDH level) (median PFS: 2.6 vs. 8.3 months, respectively; p = 0.0124). Aflibercept was well tolerated, with a manageable toxicity profile.

Conclusions

Bearing in mind the differences in sample size, the PFS achieved with the aflibercept + FOLFIRI regimen in the real-life practice setting is comparable to that observed in the clinical trial setting.

     

Dissimilarity between sporadic,non-BRCA1/2 families and hereditary breast cancer,linked to BRCA genes,in the Tunisian population

Background

Most breast cancers (90 %) are sporadic. Only 5–10 % of all cancer cases can be attributed to genetic defects. BRCA genes are strongly incriminated in the hereditary predisposition to the disease. The purpose of our study was to provide more efficient approach to identify pathogenic BRCA mutation carriers and to determine subgroups within the non-BRCA tumor class.

Methods

Different clinicopathological features, reproductive factors, as well as psychosocial ones were compared in women carrying mutations in the BRCA1/BRCA2 genes (12 cases) with non-BRCA1/2 family tumors (36 cases) and age-matched sporadic cases, unselected for family history (44 cases).

Results

A BRCA‐related class was yielded based on age at diagnosis (age ≤ 35 years; p = 0.1), molecular subtypes(the triple-negative subtype was predominant: 43 % of cases; p = 0.025) and age at menarche (p = 0.04). Furthermore, a “probably sporadic” class was distinguished using hormonal contraceptive use (through 30–40 years of age; p = 0.039), the number of full-term pregnancies (age ≥40 years; p = 0.01), age at menopause(age > 50 years; p = 0.04) and psychosocial factors (age ≥ 40 years; p = 0.01). However, analysis of non-BRCA1/2 family tumors indicated that they constitute a heterogeneous class, showing few perceptible differences with sporadic group, but distinct from BRCA1/2 tumors.

Conclusions

In Tunisian population, breast cancer can be classified with a high level of accuracy as sporadic or related to BRCA germline mutations by combining different clinicopathological features and reproductive factors. This can be clinically useful in genetic counseling and decision making for BRCA genetic test.

     

High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab

Purpose

To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab.

Methods

Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0–1) vs. group 2 with high expression (2–3).

Results

Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy.

Conclusions

Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.