E. Bastiaannet

Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data

BACKGROUND The role of adjuvant chemotherapy for patients with rectal cancer after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta-analysis of individual patient data to compare adjuvant chemotherapy with observation for patients with rectal cancer. METHODS We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference abstracts to identify European randomised, controlled, phase 3 trials comparing observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with non-metastatic rectal cancer. The primary endpoint of interest was overall survival. FINDINGS We analysed data from four eligible trials, including data from 1196 patients with (y)pTNM stage II or III disease, who had an R0 resection, had a low anterior resection or an abdominoperineal resection, and had a tumour located within 15 cm of the anal verge. We found no significant differences in overall survival between patients who received adjuvant chemotherapy and those who underwent observation (hazard ratio [HR] 0.97, 95% CI 0.81-1.17; p=0.775); there were no significant differences in overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not significantly improve disease-free survival (HR 0.91, 95% CI 0.77-1.07; p=0.230) or distant recurrences (0.94, 0.78-1.14; p=0.523) compared with observation. However, in subgroup analyses, patients with a tumour 10-15 cm from the anal verge had improved disease-free survival (0.59, 0.40-0.85; p=0.005, p(interaction)=0.107) and fewer distant recurrences (0.61, 0.40-0.94; p=0.025, p(interaction)=0.126) when treated with adjuvant chemotherapy compared with patients undergoing observation. INTERPRETATION Overall, adjuvant fluorouracil-based chemotherapy did not improve overall survival, disease-free survival, or distant recurrences. However, adjuvant chemotherapy might benefit patients with a tumour 10-15 cm from the anal verge in terms of disease-free survival and distant recurrence. Further studies of preoperative and postoperative treatment for this subgroup of patients are warranted. FUNDING None.

Association Between Age at Diagnosis and Disease-Specific Mortality Among Postmenopausal Women With Hormone Receptor–Positive Breast Cancer

CONTEXT In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. OBJECTIVE To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. DESIGN, SETTING, AND PATIENTS 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). MAIN OUTCOME MEASURES Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. RESULTS 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). CONCLUSION Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality.

Use of Aspirin postdiagnosis improves survival for colon cancer patients

Background:The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients.Methods:Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure.Results:In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001).Conclusion:Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-controlled trial that investigates the role of aspirin as adjuvant treatment in colon cancer patients.

HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma

PURPOSE The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkins lymphoma (cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown. PATIENTS AND METHODS Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and 13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA genotype data were available. RESULTS Lack of HLA class II cell-surface expression on HRS cells was observed in 41.4% and was more common in patients with extranodal disease, patients with Epstein-Barr virus-negative disease, and patients with HLA class I-negative HRS cells. Alleles of three microsatellite markers in the HLA class II region were associated with presence or absence of protein expression. In univariate analyses, lack of HLA class II expression coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027). This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40 (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95% CI, 1.22 to 5.31). CONCLUSION Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.

Better survival in patients with esophageal cancer after surgical treatment in university hospitals: A plea for performance by surgical oncologists

BackgroundIn primary esophageal cancer, studies have frequently focused on surgical patients in an effort to link outcome to hospital- or surgeon-related experience, with operative mortality used as the main outcome measure. Many studies have found an inverse relationship between operative mortality and hospital volume and surgical expertise. This study aims to assess the influence of surgeon-related expertise and hospital volume on the relative survival of operated esophageal cancer patients.MethodsFrom January 1994 to January 2002, a total of 1149 consecutive patients with primary esophageal cancer were diagnosed in the region of the Comprehensive Cancer Center North-Netherlands. As a proxy for surgeon-related expertise, hospitals in this region were categorized into three types: university, teaching nonuniversity, and nonteaching hospitals. The influence of hospital type on the relative survival of operated patients was studied by a multivariate Poisson regression model.ResultsOf the 1149 patients, 18.5% underwent surgery. There was no evidence of selective referral for surgery between the three hospital types with regard to age, tumor stage, and location. For operated patients, the 5-year relative survival was 49.2% for the university hospital versus 32.6% and 27.3% for teaching nonuniversity and nonteaching hospitals, respectively (P = .0039). When adjusted for age, tumor stage, hospital volume and referral frequency, the relative excess risk of death for the university hospital was considerably lower at .57 (95% confidence interval, .29–1.12) compared with nonteaching hospitals and .43 (95% confidence interval, .24–.76) compared with teaching nonuniversity hospitals (P = .0126).ConclusionsIn our region, patients with esophageal cancer who underwent esophagectomy in the university hospital had a markedly better relative survival compared with those who underwent surgery at teaching nonuniversity and nonteaching hospitals, emphasizing the need for referral of esophageal surgery to centers with a greater experience.

Expression of HLA Class I Antigen, Aspirin Use, and Survival After a Diagnosis of Colon Cancer

IMPORTANCE Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects. OBJECTIVE To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression. DESIGN, SETTING, AND PARTICIPANTS A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival. MAIN OUTCOMES AND MEASURES Overall survival. RESULTS The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44). CONCLUSIONS AND RELEVANCE Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

Prospective Comparison of [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography in Patients With Melanoma With Palpable Lymph Node Metastases: Diagnostic Accuracy and Impact on Treatment

PURPOSE Patients with melanoma with potentially resectable lymph node metastases require accurate staging to prevent unnecessary surgery. [(18)F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is attractive for this because melanoma typically is FDG avid. The aim of this prospective multicenter study was to perform a head-to-head comparison of FDG-PET and computed tomography (CT) in staging of patients with melanoma with palpable lymph node metastases in terms of diagnostic accuracy and impact on treatment. PATIENTS AND METHODS All consecutive patients with palpable, proven lymph node metastases of melanoma between mid 2003 and 2007 were prospectively included. The number/site of distant metastases detected with FDG-PET and CT were recorded. Histology/cytology or 6 months follow-up were the reference standard. Intended and performed treatment was recorded. RESULTS Distant metastases were suspected by FDG-PET in 32% of the 251 patients and by CT in 29% (P = .26). Upstaging was correct in 27% by FDG-PET and in 24% by CT (P = .18). FDG-PET detected more metastatic sites (133 v 112, P = .03), detecting significantly more bone and subcutaneous metastases. Treatment changed in 19% of patients; in 79% as a result of both scans, in 17% exclusively by FDG-PET, and in 4% exclusively by CT. In 34 patients (14%), FDG-PET had an additional value over spiral CT, and in 23 patients (9%), CT had additional value over FDG-PET. CONCLUSION As a result of FDG-PET and CT, 27% of patients were upstaged, and treatment changed in one of five patients. FDG-PET and CT are equivalent in upstaging; however, FDG-PET detected more metastatic sites, especially bone and subcutaneous. FDG-PET and/or CT are indicated in the staging of patients with melanoma with palpable lymph node metastases.

Risk Factors for Excess Mortality in the First Year After Curative Surgery for Colorectal Cancer

BackgroundThirty-day mortality after surgery for colorectal cancer may vastly underestimate 1-year mortality. This study aimed to quantify the excess mortality in the first postoperative year of stage I–III colorectal cancer patients and to identify risk factors for excess mortality.MethodsAll 2,131 patients who were operated with curative intent for stage I–III colorectal cancer in the western region of the Netherlands between January 1, 2006, and December 31, 2008, were analyzed. Thirty-day mortality and relative survival were calculated. In addition, relative excess risk (RER) of death was estimated by a multivariable model.ResultsThirty-day mortality was 4.9%. One-year mortality was 12.4%. Risk factors for excess mortality in the first postoperative year for colon cancer patients were emergency surgery (excess mortality 29.7%, RER 2.5, 95% confidence interval 2.5–5.0), a Charlson score of >1 (excess mortality 12.6%, RER 2.3, 95% confidence interval 1.5–3.7), stage II or III disease (excess mortality 14.9%, RER 3.9, 95% confidence interval 1.9–8.1), and postoperative adverse events (excess mortality 22.6%, RER 2.1, 95% confidence interval 1.4–3.2).ConclusionsThe 30-day mortality rate highly underestimates the risk of dying in the first year after surgery, with excess 1-year mortality rates varying from 15 to 30%. This excess mortality was especially prominent in patients with comorbidities, higher stages of disease, emergency surgery, and postoperative surgical complications.

Adherence to treatment guidelines and survival in patients with early-stage breast cancer by age at diagnosis

Elderly patients with breast cancer are under‐represented in clinical studies. It is not known whether treatment guidelines, based on clinical trials, can be extrapolated to this population. The aim of this study was to assess adherence to treatment guidelines by age at diagnosis, and to examine age‐specific survival in relation to adherence to guidelines.

Clinicopathologic prognostic factors in myxoid liposarcoma : A retrospective study of 49 patients with long-term follow-up

BackgroundThe main goal of this retrospective study was to investigate prognostic factors influencing the survival of myxoid liposarcoma (MLS) with emphasis on the role of transitional areas (TLS) and round cell morphology (RCLS).MethodsFrom 1977 to 2004, 49 patients—28 men (57%) and 21 women (43%) with a median age of 44 years (range, 7–83 years)—were diagnosed with an MLS. In 42 patients, the histology could be reviewed, and tumors were classified as MLS, TLS, or RCLS. Clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods.ResultsThe median follow-up of 49 patients was 101 months (range, 4–550 months). Of the 42 patients for whom histology was reviewed, 16 tumors were classified as MLS (38%), 19 as TLS (45%), and 7 as RCLS (17%). Sixteen patients (33%) developed a local recurrence after a median follow-up of 21 months (range, 2–108 months). Thirteen patients (27%) developed metastases. The median interval between diagnosis and metastasis was 41 months (range, 0–222 months). Median survival after metastasis was 18 months (range, 1–179 months). The 5- and 10-year disease-specific survival rates were 85% and 72%, whereas the 5- and 10-year overall survival rates were 83% and 68%, respectively. Age at presentation (P = .02), tumor grade (P = .01), and tumor size (P = .005) were significant prognostic factors associated with survival. Tumor grade was the only independent prognostic variable that remained significant with multivariate analysis. A TLS presentation had no negative influence on patient survival.ConclusionsAge at presentation, tumor grade, and tumor size had a negative influence on survival by univariate analysis, whereas tumor grade was the only independent prognostic factor by multivariate analysis. TLS was not associated with poor outcome.