| 11. |
- Papamichael, D., et al.
(author)
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Treatment of colorectal cancer in older patients : International Society of Geriatric Oncology (SIOG) consensus recommendations 2013
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:3, s. 463-476
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Research review (peer-reviewed)abstract
- Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in Europe and worldwide, with the peak incidence in patients >70 years of age. However, as the treatment algorithms for the treatment of patients with CRC become ever more complex, it is clear that a significant percentage of older CRC patients (>70 years) are being less than optimally treated. This document provides a summary of an International Society of Geriatric Oncology (SIOG) task force meeting convened in Paris in 2013 to update the existing expert recommendations for the treatment of older (geriatric) CRC patients published in 2009 and includes overviews of the recent data on epidemiology, geriatric assessment as it relates to surgery and oncology, and the ability of older CRC patients to tolerate surgery, adjuvant chemotherapy, treatment of their metastatic disease including palliative chemotherapy with and without the use of the biologics, and finally the use of adjuvant and palliative radiotherapy in the treatment of older rectal cancer patients. An overview of each area was presented by one of the task force experts and comments invited from other task force members.
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| 12. |
- Petridou, E T, et al.
(author)
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Socioeconomic disparities in survival from childhood leukemia in the United States and globally : a meta-analysis
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:3, s. 589-597
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite advancements in the treatment of childhood leukemia, socioeconomic status (SES) may potentially affect disease prognosis. This study aims to evaluate whether SES is associated with survival from childhood leukemia.METHODS: The US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) 1973-2010 data were analyzed; thereafter, results were meta-analyzed along with those from survival (cohort) studies examining the association between SES indices and survival from childhood leukemia (end-of-search date: 31 March 2014). Random-effects models were used to calculate pooled effect estimates (relative risks, RRs); meta-regression was also used.RESULTS: We included 29 studies yielding 28 804 acute lymphoblastic leukemia (ALL), 3208 acute myeloblastic leukemia (AML) and 27 650 'any' leukemia (denoting joint reporting of all subtypes) cases. According to individual-level composite SES indices, children from low SES suffered from nearly twofold higher death rates from ALL (pooled RR: 1.83, 95% confidence interval 1.00-3.34, based on four study arms); likewise, death RRs derived from an array of lower area-level SES indices ranged between 1.17 and 1.33 (based on 11 study arms). Importantly, the survival gap between higher and lower SES seemed wider in the United States, with considerably (by 20%-82%) increased RRs for death from ALL in lower SES. Regarding AML, poorer survival was evident only when area-level SES indices were used. Lastly, remoteness indices were not associated with survival from childhood leukemia.CONCLUSION: Children with lower SES suffering childhood leukemia do not seem to equally enjoy the impressive recent survival gains. Special health policy strategies and increased awareness of health providers might minimize the effects of socioeconomic disparities.
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| 13. |
- Sclafani, F., et al.
(author)
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Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer : results of the EXPERT-C trial
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:9, s. 1936-1941
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Journal article (peer-reviewed)abstract
- Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.
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| 14. |
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| 15. |
- Tobin, N. P., et al.
(author)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Journal article (peer-reviewed)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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| 16. |
- van Gijn, W., et al.
(author)
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Nomograms to predict survival and the risk for developing local or distant recurrence in patients with rectal cancer treated with optional short-term radiotherapy
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:5, s. 928-935
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Journal article (peer-reviewed)abstract
- Background: In many European countries, short-term 5 x 5 Gy radiotherapy has become the standard preoperative treatment of patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up. Patients and methods: From patient's data from three European rectal cancer trials (N = 2881), we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (total mesorectal excision/conventional surgery), surgery type (low anterior resection/abdominoperineal resection), time from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN-stage and surgical complications. Results: Pathological T-and N-status are of vital importance for an accurate prediction of LR, DM and OS. Short-course radiotherapy reduces the rate of LR. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for outcome. Conclusion: The developed nomograms can contribute to better individual risk prediction for LR, DM and OS for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up.
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| 17. |
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| 18. |
- Aaltonen, K. E., et al.
(author)
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Gene expression of breast cancer related genes in circulating tumour cells (CTCs) from patients with metastatic breast cancer
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 26:Suppl. 3, s. 15-15
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Journal article (peer-reviewed)abstract
- Introduction: Detection of circulating tumour cells (CTCs) in peripheral blood has an established prognostic significance in patients with metastatic breast cancer. Change in the number of detected CTCs is also an indication of response to therapy. Characterisation of CTCs could provide easily accessible treatment predictive information of present cancer cells within the patient and could reveal important knowledge about the metastatic process. The aim of this pilot study was to characterize CTCs with regard to both treatment predictive and more experimental markers by analysing the expression of genes associated with breast cancer.Methods: Blood samples from twelve patients with metastatic breast cancer included in the ongoing CTC-MBC study at Lund University, Sweden (Clinical Trials Id. NCT01322893) were analysed in this pilot study. Systemic treatment included endocrine, targeted and chemotherapy regimen. Blood samples were collected before start of 1st line therapy and at four time points. If progression occurred, a new round of samples was taken. CTCs were isolated from whole blood using the commercial kits AdnaTest EMT1/stem cell and AdnaTest EMT2/stem cell (AdnaGen AG, Langenhagen, Germany). With this method, CTCs are captured using antibodies directed against EpCAM and MUC-1 (EMT1-kit) or EpCAM, HER2 and EGFR (EMT2-kit). Gene expression analyses from CTCs at each time point was performed by TATAA Biocenter (Gothenburg, Sweden) using qPCR. 38 breast cancer related genes were analysed including the oestrogen receptor (ESR), HER2, VEGFR2, ALDH1, PI3K, PTEN and TWIST1.Results: Using positive expression of pseudo-markers EpCAM, MUC1 and HER2 as definition of CTCs, 6 of 12 patients were positive for CTCs. However, gene expression of additional markers in potential CTCs suggests complex patterns such as an increase in TWIST1, ALDH1 and SATB1 at time of progression.Conclusions: We present gene expression data from CTCs isolated before and during therapy in metastatic breast cancer patients. This type of characterisation could provide information of importance for treatment response and clinical outcome.Clinical trial identification: NCT01322893, March 24 2011
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