Regarding the continuous changes in the diagnostic process and treatment of colorectal cancer (CRC), it is important to evaluate long‐term trends which are relevant in giving direction for further ...research and innovations in cancer patient care. The aim of this study was to analyze developments in incidence, treatment and survival for patients diagnosed with CRC in the Netherlands. For this population‐based retrospective cohort study, all patients diagnosed with CRC between 1989 and 2014 in the Netherlands were identified using data of the nationwide population‐based Netherlands Cancer Registry (n = 267,765), with follow‐up until January 1, 2016. Analyses were performed for trends in incidence, mortality, stage distribution, treatment and relative survival measured from the time of diagnosis. The incidence of both colon and rectal cancer has risen. The use of postoperative chemotherapy for Stage III colon cancer increased (14–60%), as well as the use of preoperative (chemo)radiotherapy for rectal cancer (2–66%). The administration of systemic therapy and metastasectomy increased for Stage IV disease patients. The 5‐year relative survival increased significantly from 53 to 62% for colon cancer and from 51 to 65% for rectal cancer. Ongoing advancements in treatment, and also improvement in other factors in the care of CRC patients—such as diagnostics, dedicated surgery and pre‐ and postoperative care—lead to a continuous improvement in the relative survival of CRC patients. The increasing incidence of CRC favors the implementation of the screening program, of which the effects should be monitored closely.
What's new?
To best inform new directions for cancer management, it's important to study historical trends. Here, the authors analyzed 25 years of data in The Netherlands on colorectal cancer incidence, treatment and survival. During the period from 1989 to 2014, both incidence and 5‐year relative survival increased. Certain treatments also became more common, such as postoperative chemotherapy for Stage III patients and systemic therapy and surgical removal of metastases for Stage IV patients. Improved diagnostics and treatments have helped more patients survive, and the rising incidence of CRC supports the use of the nationwide screening program, introduced by the Dutch government in 2014.
Purpose
This population-based study determined the cumulative incidence (CI) of local, regional, and distant recurrences, examined metastatic patterns, and identified risk factors for recurrence ...after curative treatment for CRC.
Methods
All patients undergoing resection for pathological stage I–III CRC between January 2015 and July 2015 and registered in the Netherlands Cancer Registry were selected (
N
= 5412). Additional patient record review and data collection on recurrences was conducted by trained administrators in 2019. Three-year CI of recurrence was calculated according to sublocation (right-sided: RCC, left-sided: LCC and rectal cancer: RC) and stage. Cox competing risk regression analyses were used to identify risk factors for recurrence.
Results
The 3-year CI of recurrence for stage I, II, and III RCC and LCC was 0.03 vs. 0.03, 0.12 vs. 0.16, and 0.31 vs. 0.24, respectively. The 3-year CI of recurrence for stage I, II, and III RC was 0.08, 0.24, and 0.38. Distant metastases were found in 14, 12, and 16% of patients with RCC, LCC, and RC. Multiple site metastases were found often in patients with RCC, LCC, and RC (42 vs. 32 vs. 28%). Risk factors for recurrence in stage I–II CRC were age 65–74 years, pT4 tumor size, and poor tumor differentiation whereas in stage III CRC, these were ASA III, pT4 tumor size, N2, and poor tumor differentiation.
Conclusions
Recurrence rates in recently treated patients with CRC were lower than reported in the literature and the metastatic pattern and recurrence risks varied between anatomical sublocations.
The majority of colorectal cancers (CRCs) are classified as adenocarcinoma not otherwise specified (AC). Mucinous carcinoma (MC) is a distinct form of CRC and is found in 10-15% of patients with CRC. ...MC differs from AC in terms of both clinical and histopathological characteristics, and has long been associated with an inferior response to treatment compared with AC. The debate concerning the prognostic implications of MC in patients with CRC is ongoing and MC is still considered an unfavourable and unfamiliar subtype of the disease. Nevertheless, in the past few years epidemiological and clinical studies have shed new light on the treatment and management of patients with MC. Use of a multidisciplinary approach, including input from surgeons, pathologists, oncologists and radiologists, is beginning to lead to more-tailored approaches to patient management, on an individualized basis. In this Review, the authors provide insight into advances that have been made in the care of patients with MC. The prognostic implications for patients with colon or rectal MC are described separately; moreover, the predictive implications of MC regarding responses to commonly used therapies for CRC, such as chemotherapy, radiotherapy and chemoradiotherapy, and the potential for, and severity of, metastasis are also described.
The aim of this study was to determine trends in incidence, treatment and survival of colorectal cancer (CRC) patients with synchronous metastases (Stage IV) in the Netherlands. This nationwide ...population-based study included 160,278 patients diagnosed with CRC between 1996 and 2011. We evaluated changes in stage distribution, location of synchronous metastases and treatment in four consecutive periods, using Chi square tests for trend. Median survival in months was determined, using Kaplan–Meier analysis. The proportion of Stage IV CRC patients (n = 33,421) increased from 19 % (1996–1999) to 23 % (2008–2011, p < 0.001). This was predominantly due to a major increase in the incidence of lung metastases (1.7–5.0 % of all CRC patients). During the study period, the primary tumor was resected less often in Stage IV patients (65–46 %) and the use of systemic treatment has increased (29–60 %). Also an increase in metastasectomy was found in patients with one metastatic site, especially in patients with liver-only disease (5–18 %, p < 0.001). Median survival of all Stage IV CRC patients increased from 7 to 12 months. Especially in patients with metastases confined to the liver or lungs this improvement in survival was apparent (9–16 and 12–24 months respectively, both p < 0.001). In the last two decades, more lung metastases were detected and an increasing proportion of Stage IV CRC patients was treated with systemic therapy and/or metastasectomy. Survival of patients has significantly improved. However, the prognosis of Stage IV patients becomes increasingly diverse.
IMPORTANCE: Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but ...long-term outcomes are scarce in the literature. OBJECTIVE: To explore long-term oncological outcomes and health-related quality of life (HRQL) in patients with cT1-3N0M0 rectal cancer who underwent neoadjuvant chemoradiotherapy (CRT) followed by transanal endoscopic microsurgery (TEM). DESIGN, SETTING, AND PARTICIPANTS: In this multicenter phase II feasibility study, patients with cT1-3N0M0 rectal cancer admitted to referral centers for rectal cancer throughout the Netherlands between February 2011 and September 2012 were prospectively included. These patients were to be treated with neoadjuvant CRT followed by TEM in case of good response. An intensive follow-up scheme was used to detect local recurrences and/or distant metastases. Data from validated HRQL questionnaires and low anterior resection syndrome questionnaires were collected. Data were analyzed from February 2011 to April 2017. MAIN OUTCOMES AND MEASURES: The primary study outcome of the study was the number of ypT0-1 specimens by performing TEM. Secondary outcome parameters were locoregional recurrences and HRQL. RESULTS: Of the 55 included patients, 30 (55%) were male, and the mean (SD) age was 64 (39-82) years. Patients were followed up for a median (interquartile range) period of 53 (39-57) months. Two patients (4%) died during CRT, 1 (2%) stopped CRT, and 1 (2%) was lost to follow-up. Following CRT, 47 patients (85%) underwent TEM, of whom 35 (74%) were successfully treated with local excision alone. Total mesorectal excision was performed in 16 patients (4 with inadequate responses, 8 with completion after TEM, and 4 with salvage for local recurrence). The actuarial 5-year local recurrence rate was 7.7%, with 5-year disease-free and overall survival rates of 81.6% and 82.8%, respectively. Health-related quality of life during follow-up was equal to baseline, with improved emotional well-being in patients treated with local excision (mean score at baseline, 72.0; 95% CI, 67.1-80.1; mean score at follow-up, 86.9; 95% CI, 79.2-94.7; P = .001). Major, minor, and no low anterior resection syndrome was experienced in 50%, 28%, and 22%, respectively, of patients with successful organ preservation. CONCLUSIONS AND RELEVANCE: In early-stage rectal cancer (cT1-3N0M0), CRT enables organ preservation with additional TEM surgery in approximately two-thirds of patients with good long-term oncological outcome and HRQL. This multimodality treatment triggers a certain degree of bowel dysfunction, and one-third of patients still undergo radical surgery and are overtreated by CRT.
Purpose
We explored differences in survival between primary tumor locations, hereby focusing on the role of metastatic sites in synchronous metastatic colorectal cancer (mCRC).
Methods
Data for ...patients diagnosed with synchronous mCRC between 1989 and 2014 were retrieved from the Netherlands Cancer registry. Relative survival and relative excess risks (RER) were analyzed by primary tumor location (right colon (RCC), left colon (LCC), and rectum). Metastatic sites were reported per primary tumor location. Survival was analyzed for metastatic sites combined and for single metastatic sites.
Results
In total, 36,297 patients were included in this study. Metastatic sites differed significantly between primary tumor locations, with liver-only metastases in 43%, 54%, and 52% of RCC, LCC, and rectal cancer patients respectively (
p
< 0.001). Peritoneal metastases were most prevalent in RCC patients (33%), and lung metastases were most prevalent in rectal cancer patients (28%). Regardless of the location of metastases, patients with RCC had a worse survival compared with LCC (RER 0.81, 95% CI 0.78–0.83) and rectal cancer (RER 0.73, 95% CI 0.71–0.76). The survival disadvantage for RCC remained present, even in cases with metastasectomy for liver-only disease (LCC: RER 0.66, 95% CI 0.57–0.76; rectal cancer: RER 0.84, 95% CI 0.66–1.06).
Conclusions
This study showed significant differences in relative survival between primary tumor locations in synchronous mCRC, which can only be partially explained by distinct metastatic sites. Our findings support the concept that RCC, LCC and rectal cancer should be considered distinct entities in synchronous mCRC.
Purpose
The main cause of death of colorectal cancer patients is metastatic disease. Approximately 20–25 % of the patients present with metastases at time of diagnosis. The clinical course of ...patients who develop metachronous metastases, however, is less clear. The aims of this study were to describe the incidence, treatment and survival of patients with metachronous metastases from colorectal cancer and to determine risk factors for developing metachronous metastases.
Methods
From the Netherlands Cancer Registry, patients diagnosed with colorectal carcinoma in the period 2002–2003 in North-East Netherlands were selected. Patients were followed for 5 years after diagnosis of the primary tumour. Kaplan-Meier method and Cox regression analyses were used to determine predictors for developing metastases and to analyse overall survival.
Results
In total, 333 of 1743 (19 %) patients developed metachronous metastases. The majority (83 %) of these metastases were diagnosed within 3 years, and the most frequent site was the liver. Patients with advanced stage and patients with tumours in the descending colon or in the rectum were more likely to develop metastases. Approximately 10 % of all patients underwent intentionally curative treatment for their metastases, with a 5-year survival rate of 60 %. Treatment of metastases and pathologic N (pN) status were independent prognostic factors for overall survival.
Conclusions
Site and stage of the primary tumour were predictors for developing metachronous metastases. A limited number of patients with metastatic disease were treated with a curative intent. These patients had a good prognosis. Therefore, focus should be on identifying more patients who could benefit from curative treatment.
IMPORTANCE: Bridge to elective surgery using self-expandable metal stent (SEMS) placement is a debated alternative to emergency resection for patients with left-sided obstructive colon cancer because ...of oncologic concerns. A decompressing stoma (DS) might be a valid alternative, but relevant studies are scarce. OBJECTIVE: To compare DS with SEMS as a bridge to surgery for nonlocally advanced left-sided obstructive colon cancer using propensity score matching. DESIGN, SETTING, AND PARTICIPANTS: This national, population-based cohort study was performed at 75 of 77 hospitals in the Netherlands. A total of 4216 patients with left-sided obstructive colon cancer treated from January 1, 2009, to December 31, 2016, were identified from the Dutch Colorectal Audit and 3153 patients were studied. Additional procedural and intermediate-term outcome data were retrospectively collected from individual patient files, resulting in a median follow-up of 32 months (interquartile range, 15-57 months). Data were analyzed from April 7 to October 28, 2019. EXPOSURES: Decompressing stoma vs SEMS as a bridge to surgery. MAIN OUTCOMES AND MEASURES: Primary anastomosis rate, postresection presence of a stoma, complications, additional interventions, permanent stoma, locoregional recurrence, disease-free survival, and overall survival. Propensity score matching was performed according to age, sex, body mass index, American Society of Anesthesiologists score, prior abdominal surgery, tumor location, pN stage, cM stage, length of stenosis, and year of resection. RESULTS: A total of 3153 of the eligible 4216 patients were included in the study (mean SD age, 69.7 11.8 years; 1741 55.2% male); after exclusions, 443 patients underwent bridge to surgery (240 undergoing DS and 203 undergoing SEMS). Propensity score matching led to 2 groups of 121 patients each. Patients undergoing SEMS had more primary anastomoses (104 of 121 86.0% vs 90 of 120 75.0%, P = .02), more postresection stomas (81 of 121 66.9% vs 34 of 117 29.1%, P < .001), fewer major complications (7 of 121 5.8% vs 18 of 118 15.3%, P = .02), and more subsequent interventions, including stoma reversal (65 of 113 57.5% vs 33 of 117 28.2%, P < .001). After DS and SEMS, the 3-year locoregional recurrence rates were 11.7% for DS and 18.8% for SEMS (hazard ratio HR, 0.62; 95% CI, 0.30-1.28; P = .20), the 3-year disease-free survival rates were 64.0% for DS and 56.9% for SEMS (HR, 0.90; 95% CI, 0.61-1.33; P = .60), and the 3-year overall survival rates were 78.0% for DS and 71.8% for SEMS (HR, 0.77; 95% CI, 0.48-1.22; P = .26). CONCLUSIONS AND RELEVANCE: The findings suggest that DS as bridge to resection of left-sided obstructive colon cancer is associated with advantages and disadvantages compared with SEMS, with similar intermediate-term oncologic outcomes. The existing equipoise indicates the need for a randomized clinical trial that compares the 2 bridging techniques.
Population screening for colorectal cancer (CRC) is expected to increase the number of pT1 CRCs. Local excision is an attractive treatment option, but is only oncologically safe in the absence of ...lymph node metastasis (LNM). A systematic review of the predictive value of pathological risk factors for LNM in pT1 CRC was conducted to provide data for an evidence-based decision regarding follow-up or radical surgery after local excision.
PubMed was searched for reports on predictors of LNM in pT1 CRC. Published papers written in English and containing at least 50 patients were included. Meta-analyses were performed using Review Manager 5.1.
A total of 17 studies were included involving a total of 3621 patients with available nodal status. The strongest independent predictors of LNM were lymphatic invasion (relative risk RR 5.2, 95 % confidence interval CI 4.0 - 6.8), submucosal invasion ≥ 1 mm (RR 5.2, 95 %CI 1.8 - 15.4), budding (RR 5.1, 95 %CI 3.6 - 7.3), and poor histological differentiation (RR 4.8, 95 %CI 3.3 - 6.9). Limitations of the study were: results could not be stratified according to location in the colon or rectum; very early tumors removed by polypectomy without surgical resection were not included in the meta-analysis; and included studies were primarily from Asian countries and results therefore need to be verified in Western populations.
The absence of lymphatic invasion, budding, submucosal invasion ≥ 1 mm, and poor histological differentiation were each associated with low risk of LNM. Risk stratification models integrating these factors need to be investigated further.
A highly efficacious vaccine is needed for malaria control and eradication. Immunization with Plasmodium falciparum NF54 parasites under chemoprophylaxis (chemoprophylaxis and sporozoite ...(CPS)-immunization) induces the most efficient long-lasting protection against a homologous parasite. However, parasite genetic diversity is a major hurdle for protection against heterologous strains.
We conducted a double-blind, randomized controlled trial in 39 healthy participants of NF54-CPS immunization by bites of 45 NF54-infected (n = 24 volunteers) or uninfected mosquitoes (placebo; n = 15 volunteers) against a controlled human malaria infection with the homologous NF54 or the genetically distinct NF135.C10 and NF166.C8 clones. Cellular and humoral immune assays were performed as well as genetic characterization of the parasite clones.
NF54-CPS immunization induced complete protection in 5/5 volunteers against NF54 challenge infection at 14 weeks post-immunization, but sterilely protected only 2/10 and 1/9 volunteers against NF135.C10 and NF166.C8 challenge infection, respectively. Post-immunization plasma showed a significantly lower capacity to block heterologous parasite development in primary human hepatocytes compared to NF54. Whole genome sequencing showed that NF135.C10 and NF166.C8 have amino acid changes in multiple antigens targeted by CPS-induced antibodies. Volunteers protected against heterologous challenge were among the stronger immune responders to in vitro parasite stimulation.
Although highly protective against homologous parasites, NF54-CPS-induced immunity is less effective against heterologous parasite clones both in vivo and in vitro. Our data indicate that whole sporozoite-based vaccine approaches require more potent immune responses for heterologous protection.
This trial is registered in clinicaltrials.gov, under identifier NCT02098590 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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