The value of case reports in rare oncological scenarios: mixed method analysis of colorectal metastases from breast cancer.

With improved survival of cancer patients, we increasingly encounter infrequent metastatic locations. While for the common metastatic locations both prognostic information as well as evidence-based guidelines are available, for rare locations we have to rely on anecdotal case reports, the value of which is currently unknown. Therefore, we performed a systemic literature review and compare the results with a large national real-life cohort focussed on breast cancer patients with colorectal metastases. We performed a systematic literature search for breast cancer patients with colorectal metastases. Autopsy studies were excluded. Data on stage, histological factors, treatment and outcome were extracted. All identified cases were analysed as individual patients. The real-life cohort was extracted from the nationwide Dutch pathology databank. Linkage with the Netherlands Cancer Registry provided clinical characteristics, treatment and outcome data. Survival analyses and univariate regression were performed to identify relevant features for future treatment decisions. We identified 308 patients from 207 studies in the literature, and 454 patients in the real-life cohort. Colorectal metastases were the first metastatic event in 42.5% and 47.0% respectively. Cohorts were comparable for age, gender, location and hormone status, but differed in tumour type, stage and treatment. The time to colorectal metastases was similar in both cohorts (median of 68 months), and was dependent on presence of other metastases, nodal status, and primary breast surgery. The median overall survival after development of colorectal metastases was 20.6 months (95%CI 18.0-23.1 months). Despite a potential publication bias and lack of complete data for patients in the case report series, we have shown that an extensive systematic review can provide data that are comparable to real-life data, which can be used for decision-making and informing patients. Colorectal metastases are a late event in breast cancer patients, that is not associated with a detrimental survival.

The impact of standardized structured reporting of pathology reports for breast cancer care.

PURPOSE: With the increasing complexity of modern oncological patient management and the growing amount of information needed from the pathologist, traditional narrative pathology reports (NR) do not suffice. Standardized synoptic reporting (SR) increases both completeness and readability. In the Netherlands SR for breast cancer was introduced in 2009. We explore the impact of synoptic reporting on breast cancer care. METHODS: Using data from the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, a retrospective population-based cohort study was performed. Data of breast cancer resections from 2007 to 2014 were collected to compare NR and SR for all outcome measures. Kaplan-Meier analyses and log-rank testing were used to estimate overall survival. RESULTS: Over time there was an increase from 12% to 78.9% in the use of SR. SR resulted in higher completeness of pathology reports, particularly for hormone and HER2/neu receptor status. Although there was no difference in the administration of antihormonal therapy, anti-HER2 treatment was more frequently administered to eligible patients in the SR group. An effect on overall survival could not yet be confirmed on multivariate analysis. CONCLUSIONS: We demonstrate that SR has led to more complete pathology reports, which meets the needs for precision of information in breast cancer care. This is expected to improve communication and discussions between specialists regarding parameters important for adjuvant breast cancer treatment decisions. SR thereby improves breast cancer care and leads to improved allocation of treatment based on pathologic parameters and more personalized treatment regimens.

Minimally invasive transanal surgery is safe after incomplete polypectomy of low risk T1 rectal cancer: a systematic review.

AIM: In patients who have undergone a polypectomy of a malignant rectal polyp without histopathological risk factors other than an involved or unclear resection margin, additional local excision is often performed. Evidence to support this approach is lacking. The aim of this systematic review and meta-analysis was to determine the outcome in terms of local recurrence, disease-free survival (DFS) and overall survival (OS) of additional local excision following incomplete polypectomy for low risk T1 rectal cancer. METHODS: A comprehensive search for published studies was performed. Only studies in which there was incomplete (or ≤ 1 mm) removal of pT1 rectal polyps or in which the resection plane could not be assessed were included. For each included study data on tumour stage, histological factors, surgical technique, local recurrence rate, 5-year DFS and 5-year OS were extracted. The PROSPERO registration number is CRD42017062702. RESULTS: A total of 580 studies were retrieved by the search in the MEDLINE database, Embase and the Cochrane Library. After careful appreciation, four studies were included in the analysis, comprising 102 patients of whom the majority had undeterminable (Rx) resection margins. Local excision via transanal endoscopic microsurgery was reported most frequently. Only 1% of patients developed a local recurrence. One study reported 5-year DFS and 5-year OS of 96% and 87% respectively. CONCLUSION: This study supports the use of additional local excision techniques for rectal cancer patients who underwent an incomplete polypectomy for a malignant rectal polyp in the absence of risk factors other than an uncertain resection margin.

Does pelvic radiation increase rectal cancer incidence? - A systematic review and meta-analysis.

BACKGROUND: One of the late complications associated with radiation therapy (RT) is a possible increased risk of second cancer. In this systematic review, we analysed the incidence of rectal cancer following primary pelvic cancer irradiation. METHODS: A literature search was conducted using the PubMed and EMBASE libraries. Original articles that reported on secondary rectal cancer after previous RT for a primary pelvic cancer were included. Sensitivity analyses were performed by correcting for low number of events, high risk of bias, and outlying results. RESULTS: A total of 5171 citations were identified during the literature search, 23 studies were included in the meta-analyses after screening. A pooled analysis, irrespective of primary tumour location, showed an increased risk for rectal cancer following RT (N = 403.243) compared with non-irradiated patients (N = 615.530) with a relative risk (RR) of 1.43 (95% confidence interval [CI] 1.18-1.72). Organ specific meta-analysis showed an increased risk for rectal cancer after RT for prostate (RR 1.36, 95%CI 1.10-1.67) and cervical cancer (RR 1.61, 95% CI 1.10-2.35). No relation was seen in ovarian cancer patients. The modality of RT did not influence the incidence of rectal cancer. CONCLUSIONS: This review demonstrates an increased risk for second primary rectal cancer in patients who received RT to the pelvic region. This increased risk was modest and could not be confirmed for all primary pelvic cancer sites. The present study does not provide data to change guidelines for surveillance for rectal cancer in previously irradiated patients.

Tumor response after long interval comparing 5x5Gy radiation therapy with chemoradiation therapy in rectal cancer patients.

BACKGROUND: In the era of organ preserving strategies in rectal cancer, insight into the efficacy of preoperative therapies is crucial. The goal of the current study was to evaluate and compare tumor response in rectal cancer patients according to their type of preoperative therapy. METHODS: All rectal cancer patients diagnosed between 2005 and 2014, receiving radiation therapy (RT, 5 × 5Gy; N = 764) or chemoradiation therapy (CRT; N = 5070) followed by total mesorectal excision after an interval of 5-15 weeks were retrieved from the nationwide Netherlands Cancer registry. Logistic regression was used for multivariable analysis. RESULTS: Median age of patients treated with RT was 76 years (range 28-92) compared to 64 years (range 21-92) for patients treated with CRT (P < 0.001). Patients treated with RT had a significantly lower clinical stage (P < 0.001). A complete pathologic response (ypT0N0) was found in 9.3% of patients treated with RT, significantly less than in patients treated with CRT (17.5%; odds ratio [OR] 0.37, 95% confidence interval [CI] 0.24-0.57). A good response (ypT0-1N0) was observed in 17.5% of patients treated with RT and in 22.6% of patients treated with CRT (OR 0.70, 95% CI 0.51-0.95). Histological subtype, clinical stage and distance to anus were identified as independent predictors for tumor response. CONCLUSIONS: Despite a more advanced clinical stage, complete pathologic response was more common in patients treated with CRT than in patients treated with RT. Prospective trials are needed to establish the differences in other outcome parameters, including the impact on organ preserving strategies.

Incidence of second tumors after treatment with or without radiation for rectal cancer.

Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Treatment Interval between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer Patients: A Population-Based Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients. METHODS: Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5-6 to 13-14 weeks. Kaplan-Meier curves, and logistic regression and Cox regression models were used for data analysis. RESULTS: No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7-8 weeks, pCR rates in LARC patients were higher after 9-10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03-2.37) and 11-12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15-3.26). Treatment interval did not influence OS in ET or LARC patients. CONCLUSIONS: Treatment intervals of 9-12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response.

Metastatic pattern in colorectal cancer is strongly influenced by histological subtype.

BACKGROUND: Clinical studies regarding colorectal cancer (CRC) have suggested differences in metastatic patterns between mucinous adenocarcinoma (MC), signet-ring cell carcinoma (SRCC) and the more common adenocarcinoma (AC). The current study systematically evaluates metastatic patterns of different histological subtypes in CRC patients and analyzes metastatic disease upon primary tumor localization. PATIENTS AND METHODS: A nationwide retrospective review of pathological records of 5817 patients diagnosed with CRC who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA). To substantiate clinical relevance, metastatic patterns were compared with the prospective randomized multicenter Total Mesorectal Excision (TME) trial, which investigated efficacy of preoperative radiotherapy in rectal cancer patients. RESULTS: In the autopsy study, 1675 patients had metastatic disease. MC and SRCC patients more frequently had metastatic disease (33.9% and 61.2% versus 27.6%; P < 0.0001) and had metastases at multiple sites more often compared with AC patients (58.6% and 70.7% versus 49.9%; P = 0.001). AC predominantly metastasized to the liver, and MC and SRCC more frequently had peritoneal metastases. Metastatic patterns were also related to the primary tumor site, with a high rate of abdominal metastases in colon cancer patients, whereas rectal cancer patients more often had metastases at extra-abdominal sites. Results from the TME trial confirmed findings in rectal cancer patients from the autopsy study. CONCLUSION: There are profound differences in metastatic patterns between histological subtypes and the localization of the primary tumor in CRC. Findings from this study should encourage to take these factors into account for follow-up strategies and future studies.

Prognosis and value of adjuvant chemotherapy in stage III mucinous colorectal carcinoma.

BACKGROUND: Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC. PATIENTS AND METHODS: This population-based study involved 27 251 unselected patients diagnosed with colorectal carcinoma between 1990 and 2010 and recorded in a prospective pathology-based registry. Kaplan-Meier analysis and log-rank testing were used to estimate survival. Cox proportional hazard model was used to calculate multivariate hazard ratios for death. RESULTS: MC was found in 12.3% (N = 3052) of colorectal tumors with a different distribution compared with NMC, with 24.4% located in the rectum and 54.3% in the proximal colon (versus 38.0% and 30.6%), P < 0.0001. NMC was more often classified as stage I disease than MC (20.5% versus 10.9%), P < 0.0001. After adjustments for covariates, MC was associated with a higher risk of death only when located in the rectum [hazard ratio 1.22; 95% confidence interval (CI) 1.11-1.34]. Multivariate regression analysis showed a similar survival after adjuvant chemotherapy for stage III MC and NMC patients. CONCLUSIONS: The poor prognosis for MC is only present in rectal cancer. In the adjuvant setting, there is no difference in the efficacy of chemotherapy between MC and NMC; therefore, current adjuvant treatment recommendations should not take histology into account.