Background
Nearly half of soft-tissue sarcoma (STS) patients are over the age of 65, and the behavior of cancer in these elderly patients is poorly understood. The aim of this study was to assess the ...impact of age, sarcoma histotype, grade, stage, and treatment modalities on survival of extremity STS (ESTS) patients.
Methods
Patients ≥18 years diagnosed with ESTS between 1989 and 2008 were selected from the Netherlands Cancer Registry. Survival rates and patient and treatment characteristics were analyzed for all patients. Relative survival and relative excess risk of death were estimated for young (<65 years) and older (>65 years) patients.
Results
Overall, 3066 patients were included in this study. Histotype was different between young (<65 years) and elderly (>65 years) patients (
p
< 0.001). Patients over the age of 65 were more often diagnosed with high-stage ESTS and an increasing proportion of high-grade ESTS (
p
< 0.001). The proportion of patients who received no treatment increased with age, and the elderly received fewer combined-modality treatments. Age was significantly associated with relative 5-year survival 72.7 % for younger patients and 43.8 % for the oldest elderly (>85 years). In multivariable analysis, age still remained a significant prognostic factor.
Conclusions
Different distribution of sarcoma histotypes, more high-stage and high-grade sarcomas at diagnosis, less aggressive treatment, and worse survival rates emphasize the need for optimizing sarcoma research and care of the elderly.
Background Anastomotic leakage following colorectal surgery still occurs all too frequently, and this complication is difficult to predict. A nonfunctional stoma may reduce the risk of clinically ...relevant leaks but is overtreatment for most patients. More accurate assessments of the risk of anastomotic leakage would be very helpful in tailoring treatment in colorectal surgery. Therefore, a Colon Leakage Score (CLS) was developed and tested. Material and Methods The CLS was developed based on information from the literature and expert opinions. It was tested in a retrospective cohort of consecutive patients undergoing left-sided colorectal surgery with primary anastomosis in a teaching hospital in The Netherlands. Results In the test cohort, 10 of 121 patients who were not treated with a nonfunctional stoma experienced anastomotic leakage. The mean CLS in the leakage group was 16 versus eight in the group that did not have a leak ( P < 0.01). Using receiver-operating characteristics, the area under the curve (AUC) showed that the CLS was a good predictor (AUC = 0.95, CI 0.89–1.00) of anastomotic leakage. Furthermore, logistic regression analysis with CLS as a predictor for anastomotic leakage showed an odds ratio of 1.74 (95% CI 1.32–2.28, P < 0.01). Conclusions The CLS can predict the risk of anastomotic leakage following left-sided colorectal surgery. After further validation, this score may help the surgeon make a more individualized, safer decision regarding whether to perform an anastomosis or make a (nonfunctional) stoma.
In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome.
To assess the association between age at diagnosis and breast cancer ...outcome in postmenopausal women with hormone receptor-positive breast cancer.
Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357).
Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse.
During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% <65 years, 56% 65-74 years, and 36% ≥75 years; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio HR, 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P = .06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001).
Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality.
Abstract Background & Aims Statin use has been associated with a reduced incidence of colorectal cancer, and might also affect survival of patients diagnosed with colon cancer. Statins are believed ...to inhibit Ras signaling, and also activate the bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer, and whether their effects were associated with changes in KRAS or the BMP signaling pathways. Methods Data were derived from the PHARMO database network (Netherlands) and linked to patients diagnosed with colon cancer from 2002 through 2007, listed in the Eindhoven Cancer Registry. We obtained information on causes of death from statistics Netherlands. We constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008. Survival was analyzed with statin user status after diagnosis as a time-dependent covariate. Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival. Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4, BMPR1A, BMPR1B, and BMPR2 proteins. Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A, BMPR1B, or BMPR2. DNA was isolated from tumor tissues and analyzed by quantitative PCR to detect mutations in KRAS. The primary outcome measures were overall mortality and cancer-specific mortality. Results In this cohort, 21.0% of the patients (210/999) were defined as statin users after colon cancer diagnosis. Statin use after diagnosis was significantly associated with reduced risk of death from any cause (adjusted relative risk RR, 0.67; 95% CI, 0.51–0.87; P=.003) and death from cancer (adjusted RR, 0.66; 95% CI, 0.49-0.89; P=.007). Statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling (adjusted RR, 0.39; 95% CI, 0.22–0.68; P=.001), but not for patients whose tumors did not have BMP signaling (adjusted RR, 0.81; 95% CI, 0.55–1.21; P=0.106; P<.0001 for the interaction). Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations (adjusted RR, 0.81; 95% CI, 0.56–1.18; P=.273) or whose tumors did have KRAS mutations (adjusted RR, 0.59; 95% CI 0.35–1.03; P=.062; P for the interaction=0.90). Conclusions In an analysis of 999 patients with a diagnosis of colon cancer, we associated statin with reduced risk of death from any cause or from cancer. The benefit of statin use is greater for patients whose tumors have intact BMP signaling, independent of KRAS mutation status. Randomized controlled trials are required to confirm these results.
Nonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and ...related the results to tumor expression of classical HLA class I. Our study population (n = 677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue microarray sections of arrayed tumor and normal control material were immunohistochemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I molecules was determined previously. HLA-E, HLA-G, and HLA-EG on breast tumors were classified as expression in 50, 60, and 23% of patients, respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p = 0.027), HLA-G (p = 0.035), or HLA-EG (p = 0.001) resulted in a worse relapse-free period. An interaction was found between classical and nonclassical HLA class I expression (p = 0.002), suggestive for a biological connection. We have demonstrated that, next to expression of classical HLA class I, expression of HLA-E and HLA-G is an important factor in the prediction of outcome of breast cancer patients. These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host's immune system, by up- or downregulation of HLA class Ia and class Ib loci.
Purpose
Tumour-infiltrating lymphocytes (TILs) have been shown to be prognostic for disease-free survival and predictive for the benefit of chemotherapy in patients with early breast cancer, but have ...not been studied for endocrine therapy.
Experimental design
The number of CD8-positive TILs was assessed in a subcohort of 236 patients in the Intergroup Exemestane Study. AQ After 2–3 years of adjuvant tamoxifen, AQpatients were randomized between the schemes of continuation for 5 years on tamoxifen and switching to exemestane. The numbers of CD8-positive TILs were analysed for correlations with disease-free survival (DFS) and overall survival (OS). A similar analysis was performed on 2596 patients in the TEAM trial who were randomized between the sequential scheme and the exemestane monotherapy.
Results
In the first cohort, patients with low (below median) numbers of CD8-positive TILs had a univariate hazard ratio (HR) for DFS of 0.27 (95% CI 0.13–0.55) in favour of treatment with exemestane, whereas this benefit was not observed in patients with high numbers of CD8-positive TILs (HR 1.34, 95% CI 0.71–2.50, HR for interaction 5.02,
p
= 0.001). In the second cohort, patients with low numbers of CD8-positive TILs showed a benefit of exemestane treatment on recurrence-free survival (RFS HR 0.67, 95% CI 0.45–0.99), and not with above-median numbers of CD8-positive TILs (HR 0.86, 95% CI 0.59–1.26, HR for interaction 1.29,
p
= 0.36).
Conclusions
This study is the first to propose the number of CD8-positive TILs as potential predictive markers for endocrine therapy, with the low presence of CD8-positive TILs associated to benefit for exemestane-inclusive therapy. However, treatment-by-marker interactions were only significant in one cohort, indicating the need for further validation.
Aims
Epigenetic changes are of crucial importance in cancer development and are potentially reversible; they are therefore targets of interest for anti‐cancer therapy. The aim of this study was to ...investigate the clinical prognostic value of the histone deacetylases SIRT1, HDAC1 and HDAC2 and the histone modifications H4K16Ac and H3K56Ac in colorectal cancer.
Methods and results
The epigenetic markers were immunohistochemically stained on tissue microarrays containing colorectal tumours (n = 254) and normal colorectal tissues (n = 50). Nuclear expression was assessed on the semi‐automated Ariol system. Multivariate trend survival analyses of the combined markers showed better patient survival and less tumour recurrence when more markers showed high nuclear expression. For the combination of the histone deacetylases and H3K56Ac, the hazard ratio (HR) for overall survival (OS) was 0.82 95% confidence interval (CI) 0.72–0.94; P = 0.005 and the HR for distant recurrence‐free survival (DRFS) was 0.77 (95% CI 0.64–0.92; P = 0.003) per additional marker showing high expression. Similarly, for the combination of histone deactylases and H4K16Ac, HRs of 0.86 (95% CI 0.76–0.97; P = 0.01) for OS and 0.79 (95% CI 0.68–0.93; P = 0.006) for DRFS were observed per additional marker showing high expression.
Conclusions
The studied epigenetic markers showed clinical prognostic value in colorectal cancer, both as individual markers and when combined into multimarker analyses. These results indicate that epigenetic mechanisms play an important role in colorectal carcinogenesis.
Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping of breast cancer. We performed a randomized clinical trial to ...assess the value of blue dyes when used in combination with NIR fluorescence. We also preliminarily examined the possibility of performing SLN mapping without radiotracers.
Clinical trial subjects were 24 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using 99(m) technetium-nanocolloid and received 1.6 mL of 500 μM ICG injected periareolarly. Patients were randomly assigned to undergo SLN biopsy with or without patent blue. To assess the need for radiocolloids to localize the SLN or SLNs, the surgeon did not use the handheld gamma probe during the first 15 min after the axillary skin incision.
SLN mapping was successful in 23 of the 24 patients. No significant difference was found in signal-to-background ratio between the groups with and without patent blue (8.3 ± 3.8 vs. 10.3 ± 5.7, respectively, P = 0.32). In both groups, 100 % of SLNs were radioactive and fluorescent, and in the patent blue group, only 84 % of SLNs were stained blue. In 25 % of patients, the use of the gamma probe was necessary to localize the SLN within the first 15 min.
This study shows that there is no benefit of using patent blue for SLN mapping in breast cancer patients when using NIR fluorescence and 99(m) technetium-nanocolloid. NIR fluorescence imaging outperformed patent blue in all patients.
Abstract Purpose Treatment decisions in early breast cancer can revolve around type of surgery and whether or not to have adjuvant systemic therapy. This systematic review aims to give an overview of ...patient self-reported factors affecting preferences for breast conserving surgery (BCS) versus mastectomy (MAST), the minimal benefit patients require from adjuvant chemotherapy (aCT) and/or adjuvant hormonal therapy (aHT) to consider it worthwhile, and factors influencing this minimally-required benefit. Methods PubMed and EMBASE were searched for relevant articles. Two reviewers independently selected articles and extracted data. Results We identified 15 studies on surgical and six on adjuvant systemic treatment decision-making. Factors affecting patient preference for BCS most frequently related to body image (44%), while factors influencing preference for MAST most often related to survival/recurrence (46%). To make adjuvant systemic therapy worthwhile, the median required absolute increase in survival rate was 0.1–10% and the median required additional life expectancy was 1 day to 5 years. The range of individual preferences was wide within studies. Participants in the aHT studies required larger median benefits than those in the aCT studies. Factors associated with judging smaller benefits sufficient most often (44%) related to quality of life (e.g., less treatment toxicity). Conclusion Decisive factors in patients’ preferences for surgery type commonly relate to body image and survival/recurrence. Most participants judged small to moderate benefits sufficient to consider adjuvant systemic therapy worthwhile, but individual preferences varied widely. Clinicians should therefore consider the patient’s preferences to tailor their treatment recommendations accordingly.
Immune checkpoint inhibitors (ICIs) have strongly improved the survival of melanoma patients. However, as durable response to ICIs are only seen in a minority, there is an unmet need to identify ...biomarkers that predict response. Therefore, we provide a systematic review that evaluates all biomarkers studied in association with outcomes of melanoma patients receiving ICIs. We searched Pubmed, COCHRANE Library, Embase, Emcare, and Web of Science for relevant articles that were published before June 2020 and studied blood, tumor, or fecal biomarkers that predicted response or survival in melanoma patients treated with ICIs. Of the 2536 identified reports, 177 were included in our review. Risk of bias was high in 40%, moderate in 50% and low in 10% of all studies. Biomarkers that correlated with response were myeloid-derived suppressor cells (MDSCs), circulating tumor cells (CTCs), CD8+ memory T-cells, T-cell receptor (TCR) diversity, tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), and a favorable gut microbiome. This review shows that biomarkers for ICIs in melanoma patients are widely studied, but heterogeneity between studies is high, average sample sizes are low, and validation is often lacking. Future studies are needed to further investigate the predictive utility of some promising candidate biomarkers.
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