Factors Associated with “Survivor Identity” in Men with Breast Cancer

Cancer patients vary in their comfort with the label “survivor”. Here, we explore how comfortable males with breast cancer (BC) are about accepting the label cancer “survivor”. Separate univariate logistic regressions were performed to assess whether time since diagnosis, age, treatment status, and cancer stage were associated with comfort with the “survivor” label. Of the 70 males treated for BC who participated in the study, 58% moderately-to-strongly liked the term “survivor”, 26% were neutral, and 16% moderately-to-strongly disliked the term. Of the factors we explored, only a longer time since diagnosis was significantly associated with the men endorsing a survivor identity (OR = 1.02, p = 0.05). We discuss how our findings compare with literature reports on the comfort with the label “survivor” for women with BC and men with prostate cancer. Unlike males with prostate cancer, males with BC identify as “survivors” in line with women with BC. This suggests that survivor identity is more influenced by disease type and treatments received than with sex/gender identities.     

Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes

Introduction

The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A–like breast cancer from luminal B–like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients.

Methods

We studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with “low” (<14%), “intermediate” (14% to 19%) or “high” (≥20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status.

Results

Lack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P < 0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A–like disease.

Conclusions

The updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A–like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.     

Conditional survival estimate of acute-on-chronic hepatitis B liver failure: A dynamic prediction based on a multicenter cohort

Objectives

Counseling patients with acute-on-chronic hepatitis B liver failure (ACHBLF) on their individual risk of short-term mortality is challenging. This study aimed to develop a conditional survival estimate (CSE) for predicting individualized mortality risk in ACHBLF patients.

Methods

We performed a large prospective cohort study of 278 ACHBLF patients from December 2010 to December 2013 at three participating medical centers. The Kaplan-Meier method was used to calculate the cumulative overall survival (OS). Cox proportional hazard regression models were used to analyze the risk factors associated with OS. 4-week CSE at “X” week after diagnostic established were calculated as CS₄ = OS_(X+4)/OS_(X).

Results

The actual OS at 2, 4, 6, 8, 12 weeks were 80.5%, 71.8%, 69.3%, 66.0% and 63.7%, respectively. Using CSE, the probability of surviving an additional 4 weeks, given that the patient had survived for 1, 3, 5, 7, 9 weeks was 74%, 86%, 92%, 93%, 97%, respectively. Patients with worse prognostic feathers, including MELD > 25, Child grade C, age > 45, HE, INR > 2.5, demonstrated the greatest increase in CSE over time, when compared with the “favorable” one (Δ36% vs. Δ10%; Δ28% vs. Δ16%; Δ29% vs. Δ15%; Δ60% vs. Δ12%; Δ33% vs. Δ12%; all P < 0.001; respectively).

Conclusions

This easy-to-use CSE can accurately predict the changing probability of survival over time. It may facilitate risk communication between patients and physicians.     

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on “Head Start” III: a multi-institutional,prospective clinical trial

Background“Head Start” III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma.MethodsFollowing surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction.ResultsBetween 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% for classic and 38 ± 13% and 46 ± 14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ± 8% for ND and 21 ± 5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average.ConclusionWe report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.     

Towards precision oncology in angiosarcomas using next generation “omic” technologies

Angiosarcomas are a group of aggressive tumors of vascular origin. Although thought to be a rare cancer constituting just 1–2% of all soft tissue sarcomas, recent observations suggest that angiosarcomas are more common amongst Asian populations as compared to the West, suggesting the possibility of distinct genetic or environmental triggers influencing its pathogenesis. Advances in genomic sequencing efforts have led to the discovery of ultraviolet mutation signatures and high tumor mutation burden as common features of angiosarcoma of the head and neck. In addition, multi-omic analyses integrated with clinical data identified 3 subtypes characterized by distinctive etiological and biological phenotypes, with potential implications on precision therapy. The systemic and local immune milieu, as well as the presence of “giant” tumor cells, was also recently demonstrated to influence clinical behavior and patient outcomes, further highlighting complexities of this disease. Improvements in next generation “omic”-based technologies are expected to improve our understanding of angiosarcoma and guide the development of precision oncology in this rare cancer.     

Surrogacy Beyond Prognosis: The Importance of “Trial-Level” Surrogacy

Many candidate surrogate endpoints are currently assessed using a 2-level statistical approach, which consists in checking whether (1) the potential surrogate is associated with the final endpoint in individual patients and (2) the effect of treatment on the surrogate can be used to reliably predict the effect of treatment on the final endpoint. In some situations, condition (1) is fulfilled but condition (2) is not. We use concepts of causal inference to explain this apparently paradoxical situation, illustrating this review with 2 contrasting examples in operable breast cancer: the example of pathological complete response (pCR) and that of disease-free survival (DFS). In a previous meta-analysis, pCR has been shown to be a strong and independent prognostic factor for event-free survival (EFS) and overall survival (OS) after neoadjuvant treatment of operable breast cancer. Yet, in randomized trials, the effects of experimental treatments on pCR have not translated into predictable effects on EFS or OS, making pCR an “individual-level” surrogate, but not a “trial-level” surrogate. In contrast, DFS has been shown to be an acceptable surrogate for OS at both the individual and trial levels in early, HER2-positive breast cancer. The distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.

Many candidate surrogate endpoints are currently assessed using a two-level statistical approach. This article explores tentative surrogates versus actual outcomes, focusing on the “surrogate paradox”.

Implications for PracticeThe distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.     

Perspective on Cancer Control: Whither the Tobacco Endgame for Canada?

Aims: In 2014, in response to evidence that Canada’s tobacco use would lead, inexorably, to substantial morbidity and mortality for the foreseeable future, a group of experts convened to consider the development of a “Tobacco Endgame” for Canada. The “Tobacco Endgame” defines a time frame in which to eliminate structural, political, and social dynamics that sustain tobacco use, leading to improved population health. Strategies: A series of Background Papers describing possible measures that could contribute to the creation of a comprehensive endgame strategy for Canada was prepared in advance of the National Tobacco Endgame Summit hosted at Queen’s University in 2016. At the summit, agreement was reached to work together to achieve <5% tobacco use by 2035 (<5 by ’35). A report of the proceedings was shared widely. Achievements: Progress since 2016 has been mixed. The Summit report was followed by a national forum convened by Health Canada in March 2017, and in 2018, the Canadian Government adopted “<5 × ’35” tobacco use target in a renewed Canadian tobacco reduction strategy. Tobacco use has declined in the last 5 years, but at a rate slower than that which will be needed to achieve the <5 by ’35 goal. There remain > 5 million smokers in Canada, signaling that smoking-related diseases will continue to be an enormous health burden. Furthermore, the landscape of new products (e-cigarettes and cannabis) has created additional risks and opportunities. Future directions: A bold, reinvigorated tobacco control strategy is needed that significantly advances ongoing policy developments, including full implementation of the key demand-reduction policies of the WHO Framework Convention on Tobacco Control. Formidable, new disruptive policies and regulations will be needed to achieve Canada’s Endgame goal.     

“We’re on a Merry-Go-Round”: Reflections of Patients and Carers after Completing Treatment for Sarcoma

Sarcoma is a rare cancer that has a significant impact on patients’ and carers’ quality of life. Despite this, there has been a paucity of research exploring the diverse experiences of patients and carers following sarcoma treatment. The aim of this study was to explore patients’ and carers’ reflections on life after treatment for sarcoma. A qualitative research design with a social constructionist epistemology was used. Participants included patients previously treated for sarcoma (n = 21) and family carers of patients treated for sarcoma (n = 16). Participants completed semi-structured interviews which were analysed using thematic analysis. Three primary themes were identified: “This journey is never going to be over”, “But what happens when I am better?”, and finding a silver lining. Participants represented sarcoma as having a long-term, and sometimes indefinite, threat on their life that they had limited control over. Conclusions: This study highlight the heterogeneous and ongoing needs of sarcoma survivors and their families. Patients and carers strove to translate their experiences in a meaningful way, such as by improving outcomes for other people affected by sarcoma. Parental carers in particular attempted to protect the patient from the ongoing stress of managing the disease.     

Prospective evaluation of unmet needs of rural and aboriginal cancer survivors in Northern British Columbia

Background

The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities.

Methods

We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing “no unmet need” and 4 representing “very high unmet need.” A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results.

Results

We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss.

Conclusions

First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations.     

The biology of the tumor microenvironment in DLBCL: Targeting the “don’t eat me” signal

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma with biologically and clinically heterogeneous features. Recently, the tumor microenvironment of this disease has been recognized as an important biological aspect of tumor development and therapeutic targets. Recurrent genetic alterations play significant roles in immune recognition of lymphoma cells. In particular, novel genetic alterations promoting phagocytosis were identified, suggesting a potential therapeutic strategy targeting the “don’t eat me” signal.     

Immunohistochemical detection of the expression of the cell adhesion molecules E-cadherin, desmoglein-2, beta4-integrin, ICAM-1 and HCAM (CD44s) in Warthin's tumour of the parotid gland

The study of the expression of cell adhesion molecules (CAMs), E-cadherin, desmoglein-2, beta4-integrin, HCAM (CD44s) and ICAM-1 in Warthin's tumours. Twenty formalin--fixed, paraffin--embedded parotid Warthin's tumours were studied using an Envision/HRP immunohistochemical technique. Beta4-integrin was strongly expressed in all cell-basement membrane and intercellular contacts of the epithelium, E-cadherin and desmoglein-2 in cell-cell contacts, but not in basal cell-basement membrane connections and on columnar cells' luminal surfaces, HCAM (CD44s) in intercellular contacts of both luminal (mainly), basal cells and also in the periphery of monocytic-lymphocytic stroma, and ICAM-1 was weak to moderate expressed in both luminal and basal epithelial cells and strongly in the germinal lymphocytic centres. CAM expression suggests a bilayered excretory ductal structure of the neoplastic epithelium in Warthin's tumour, as a result of hyperplastic process of the glandular epithelium that interacts with the excessive lymphoid tissue of the stroma.     

The real-world performance of ThyroSeqV.2 to diagnose thyroid “neoplasm requiring surgery”

Fine-needle biopsy (FNB) predicts benign or malignant thyroid nodules. For indeterminate (ITN) FNBs, commercial molecular tests may improve the diagnostic accuracy and reduce the number of operations. These tests have had limited independent implementation studies in routine clinical practice. This is a prospective observational study. At Boston Medical Center, the 1,316 consecutive FNBs were classified to one of the six categories in the Bethesda classification system. Those ITN samples were submitted for ThyroSeqV.2 next generation sequencing panel analysis. The performance of ThyroSeqV.2 to predict “neoplasm requiring surgery” (NRS) was evaluated. ThyroSeqV.2 assay was performed in 398 FNBs on 384 cytologically ITN nodules (308 Bethesda III, 47 Bethesda IV and 29 Bethesda V). The first evaluable ThyroSeq result for each nodule was used for final analysis. Seventy-seven (72.0%) of 107 patients with a high risk molecular test underwent thyroid surgery resulting in 41 NRS (53.2%) and 36 benign nodules (46.8%). Of the 249 patients with a low risk or negative molecular analysis, 51 (20.5%) had surgery revealing 47 benign nodules (92.2%) and 4 NRS (7.8%). Based on surgical outcome of 128 ITN with evaluable ThyroSeq results, this molecular test had a sensitivity of 91% (95% CI: 79%-98%), specificity of 56% (45%-67%), positive predictive value (PPV) of 53% (42%-65%), negative predictive value (NPV) of 92% (81%-98%), and an overall accuracy of 69% (55%-85%) with a prevalence of NRS of 35% (27%-44%). ThyroSeqV.2 in this clinical use study in ITN nodules provided a similar NPV but a lower PPV than expected compared to published studies due to the detection of an array of mutations in benign nodules. The NPV of 92.0% for ITN cytology confirmed its utility as a “rule-out” test to exclude NRS.     

International study on inter-reader variability for circulating tumor cells in breast cancer

Introduction

Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement.

Methods

CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test.

Results

For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90).

Conclusions

The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.     

Secondary colon cancer in patients with ulcerative colitis: a systematic review and meta-analysis

BackgroundA meta-analysis was conducted on the incidence of colon cancer in patients with ulcerative colitis (UC). This study aimed to evaluate the correlation between UC and colon cancer, and provide a theoretical guidance for clinical diagnoses and treatments of UC.MethodsArticles were searched in Chinese database with “ulcerative colitis”, “UC”, “colon cancer”, “colorectal cancer”, “incidence”, and “meta-analysis” as the search terms. Articles were searched in English database with “ulcerative colitis”, “UC”, “colon cancer”, “incidence rate”, and “meta-analysis” as the search terms. Moreover, articles with the topic of “correlation between UC and colon cancer” were screened. The quality of articles was assessed using Rev Man 5.3 software provided by Cochrane system.ResultsEleven articles were included, most of which were of medium and high quality. Results of meta-analysis showed that 12,216 patients with UC were included in this study, and 110 patients developed colon cancer. There was statistical heterogeneity (Chi²=103.10, I²=90%, P<0.00001). Random-effect model analyses showed that there were no significant differences between colon cancer in patients with UC and those without colon cancer (Z=12.44, P<0.00001). A systematic review of articles found that the course and development of colon cancer in patients with UC might affect the occurrence of colon cancer. UC was a risk factor for colorectal cancer.DiscussionIt was found that the course of disease and the occurrence and development of UC might affect the occurrence of colon cancer through a systematic review of articles. UC was one of the risk factors of colorectal cancer.     

Prognostic impact of circulating tumor cells detected with the microfluidic “universal CTC‐chip” for primary lung cancer

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, “CTC‐chip,” for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM‐chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression‐free survival (P = .037) and cancer‐specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression‐free survival was worse in CTC‐positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM‐chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.     

Diagnosing lung cancer in the 21st century: are we ready to meet the challenge of individualized care?

Background

Histologic and molecular subtyping have become increasingly important as predictors of treatment benefit in lung cancer. The objective of the present study was to determine whether current diagnostic approaches provide adequate tissue to allow for individualized treatment decisions.

Methods

Our retrospective cohort study of new lung cancer patients seen at an academic centre between July 2007 and June 2008 collected baseline demographic and diagnostic information, including mode of diagnosis, type of diagnostic material, and pathology diagnosis.

Results

Of the 431 study patients, 20% had stage i or ii non-small-cell lung cancer (nsclc), 24% stage iii disease, and 39% stage iv nsclc. Three quarters of the small-cell lung cancer (sclc) cases were extensive stage. Diagnostically, 18% of patients had sclc; 30%, adenocarcinoma; 27%, squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma; 1%, mixed histology; 18%, nsclc not otherwise specified; 4%, other; and 2%, no pathology diagnosis. Surgical pathology material was available in 80% of cases, and cytology material alone in 20%. Surgical pathology material was more common in patients with early-stage than with advanced disease (89% for stages i and ii vs. 74% for stages iii and iv, p < 0.0001). The pathology report included ambiguous terms in 24% of cases: “consistent” (12%), “suspicious” (3%), “favour” (2%), “suggestive” (2%), “likely” (1%), “compatible” with malignancy (1%), “at least” (1%), “atypical” (0.5%), and “no pathology” (1.5%).

Conclusions

Current diagnostic approaches in most lung cancer patients appear adequate, but complete histopathologic identification is missing in nearly 20% of cases, and some uncertainty as to the final diagnosis is expressed in 24% of pathology reports. Some improvement in diagnostic sampling and pathology reporting are required to allow for implementation of current treatment approaches.     

The in situ local immune response,tumour senescence and proliferation in colorectal cancer

Background:

Immune cell infiltrates are important determinants of colorectal cancer (CRC) outcome. Their presence may be driven by tumour or host-specific factors. From previous studies in mice, senescence, a state of cell cycle arrest, may moderate tumour progression through upregulation of antitumour immune responses. The relationships between senescence and immune infiltrates have not previously been studied in humans. We explore whether a marker of senescence (p16^ink4a) in combination with low level expression of a proliferation marker (ki-67) relate to T cell infiltrates in CRC, and whether p16^ink4a, Ki-67 and immune infiltrates have similar prognostic value.

Methods:

Immunostaining of p16^inka and Ki-67 was performed within a CRC tissue microarray. Nuclear p16^inka and Ki-67 were categorised as high/low. T-cell markers, CD3, CD45RO, CD8 and FOXP3 were scored separately as high/low grade in three areas of the tumour: the invasive margin (IM), tumour stroma and cancer cell nests (CCNs).

Results:

Two hundred and thirty stage I–III cancers were studied. High nuclear p16^ink4a was expressed in 63% and high proliferation (Ki-67 >15%) in 61%. p16^ink4a expression was associated with reduced CD45RO+ cells at the IM (P<0.05) and within the stroma (P<0.05) and reduced CD8+ cells at the IM (P<0.01). A low Ki-67 proliferative index was associated with reduced density of CD3+ cells in CCNs (P<0.01), reduced CD45RO+ cells at the IM (P<0.05) and within the CCNs (P<0.001), reduced FOXP3+ cells at the IM (P<0.001), within the stroma (P=0.001) and within CCNs (P<0.001) and reduced CD8+ cells at the IM (P<0.05) and within the CCNs (P<0.05). Tumours with both a low proliferative index and expression of p16^ink4a demonstrated similar consistent relationships with reduced densities of T-cell infiltrates. On multivariate analysis, TNM stage (P<0.001), low CD3 cells at the IM (P=0.014), low CD8 cells at the IM (P=0.037), low proliferation (Ki-67; P=0.013) and low senescence (p16^ink4a; P=0.002) were independently associated with poorer cancer survival.

Conclusion:

Senescence, proliferation and immune cell infiltrates are independent prognostic factors in CRC. Although related to survival, p16^ink4a-associated senescence is not associated with an upregulation of antitumour T-cell responses.