Summary 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, pinteraction =0·107) and fewer distant recurrences (0·61, 0·40–0·94; p=0·025, pinteraction =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.
New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not ...included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval CI 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.
Purpose
The number of older patients with breast cancer is rapidly increasing. A previous study showed that between 1990 and 2005, the survival of older patients with breast cancer did not improve in ...contrast to younger patients. In recent years, scientific evidence in the older age group has increased and specific guidelines for older women with breast cancer have been developed. The aim of this study was to assess changes in survival outcomes of older patients with breast cancer.
Patients and methods
All patients with breast cancer between 2000 and 2017 were included from the Netherlands cancer registry. We assessed changes in treatments using logistic regression. We calculated changes in relative survival as proxy for breast cancer mortality, stratified by age and stage.
Results
We included 239,992 patients. Relative survival improved for patients < 65 for all stages. In patients aged 65–75 years, relative survival did not improve in stage I–II but did improve in stage III breast cancer (RER 0.98, 95% CI 0.96–1.00,
p
= 0.046). Concurrently, prescription of systemic treatments increased. In patients > 75, relative survival did not improve in patients with stage I/II or stage III disease, nor did treatment strategies change.
Conclusions
This study shows that relative survival of patients aged 65–75 years with advanced breast cancer has improved, and concurrently, prescription of systemic treatment increased. To improve survival of patients > 75 as well, future studies should focus on individualizing treatments based on concomitant comorbidity, geriatric parameters and the risk of competing mortality and toxicity of treatments.
Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival ...outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival.
Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated.
In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30-6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium.
There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.
Individualized selection of patients with early-stage hormone receptor-positive (HR
) breast cancer for extended endocrine therapy (EET) is required to balance modest gains in outcome with toxicities ...of prolonged use. This study examined the Breast Cancer Index BCI; HOXB13/IL17BR ratio (H/I) as a predictive biomarker of EET benefit in patients from the Investigation on the Duration of Extended Adjuvant Letrozole trial.
BCI was tested in primary tumor specimens from 908 patients randomized to receive 2.5 versus 5 years of extended letrozole. The primary endpoint was recurrence-free interval. Cox models and likelihood ratios tested the interaction between EET and BCI (H/I).
BCI (H/I)-high significantly predicted benefit from extended letrozole in the overall cohort HR 0.42; 95% confidence interval (CI), 0.21-0.84;
= 0.011 and any aromatase inhibitor subset HR 0.34; 95% CI, 0.16-0.73;
= 0.004), whereas BCI (H/I)-low patients did not derive significant benefit (HR 0.95; 95% CI, 0.58-1.56;
= 0.84 and HR 0.90; 95% CI, 0.53-1.55;
= 0.71, respectively) treatment to biomarker interaction was significant (
= 0.045,
= 0.025, respectively). BCI identified approximately 50% of patients with clinically high-risk disease that did not benefit, and with clinically low-risk disease that derived significant benefit, from an additional 2.5 years of EET.
BCI (H/I) predicted preferential benefit from 5 versus 2.5 years of EET and identified patients with improved outcomes from completing 10 years of adjuvant endocrine therapy. Findings expand the clinical utility of BCI (H/I) to a broader range of patients and beyond prognostic risk factors as a predictive endocrine response biomarker for early-stage HR
breast cancer.
Hormone receptor (HR)-positive, HER2/neu-negative breast cancers have a sustained risk of recurrence up to 20 years from diagnosis. TEAM (Tamoxifen, Exemestane Adjuvant Multinational) is a large, ...multi-country, phase III trial that randomized 9776 women for the use of hormonal therapy. Of these 2754 were Dutch patients. The current study aims for the first time to correlate the ten-year clinical outcomes with predictions by CanAssist Breast (CAB)-a prognostic test developed in South East Asia, on a Dutch sub-cohort that participated in the TEAM. The total Dutch TEAM cohort and the current Dutch sub-cohort were almost similar with respect to patient age and tumor anatomical features.
Of the 2754 patients from the Netherlands, which are part of the original TEAM trial, 592 patients' samples were available with Leiden University Medical Center (LUMC). The risk stratification of CAB was correlated with outcomes of patients using logistic regression approaches entailing Kaplan-Meier survival curves, univariate and multivariate cox-regression hazards model. We used hazard ratios (HRs), the cumulative incidence of distant metastasis/death due to breast cancer (DM), and distant recurrence-free interval (DRFi) for assessment.
Out of 433 patients finally included, the majority, 68.4% had lymph node-positive disease, while only a minority received chemotherapy (20.8%) in addition to endocrine therapy. CAB stratified 67.5% of the total cohort as low-risk DM = 11.5% (95% CI, 7.6-15.2) and 32.5% as high-risk DM = 30.2% (95% CI, 21.9-37.6) with an HR of 2.90 (95% CI, 1.75-4.80; P < 0.001) at ten years. CAB risk score was an independent prognostic factor in the consideration of clinical parameters in multivariate analysis. At ten years, CAB high-risk had the worst DRFi of 69.8%, CAB low-risk in the exemestane monotherapy arm had the best DRFi of 92.7% vs CAB high-risk, HR, 0.21 (95% CI, 0.11-0.43), P < 0.001, and CAB low-risk in the sequential arm had a DRFi of 84.2% vs CAB high-risk, HR, 0.48 (95% CI, 0.28-0.82), P = 0.009.
Cost-effective CAB is a statistically robust prognostic and predictive tool for ten-year DM for postmenopausal women with HR+/HER2-, early breast cancer. CAB low-risk patients who received exemestane monotherapy had an excellent ten-year DRFi.
Objective
This study aimed to assess psychological functioning, quality of life, and regret about screening after a positive fecal immunochemical test (FIT) and subsequent colonoscopy, and to ...evaluate changes over time.
Methods
This is a prospective cohort study. Individuals aged 55 to 75 with a positive FIT that were referred for colonoscopy between July 2017 and November 2018, were invited to complete questionnaires related to psychological distress and health‐related quality of life at three predefined time points: before colonoscopy, after histopathology result notification, and after 6 months. Four questionnaires were used: the Psychological Consequences Questionnaire (PCQ), the six‐item Cancer Worry Scale (CWS), the Decision Regret Scale (DRS), and the 36‐item Short‐Form (SF‐36).
Results
A total of 1066 participants out of 2151 eligible individuals were included. Patients with cancer showed a significant increase in psychological dysfunction (P = .01) and cancer worry (P = .008) after colonoscopy result notification, and a decline to pre‐colonoscopy measurements after 6 months. In the no‐cancer groups, psychological dysfunction and cancer worry significantly decreased over time (P < .05) but there was no ongoing decline. After 6 months, 17% of participants with no cancer experienced high level of cancer worry (CWS ≥ 10). Yet, only 5% reported high level of regret about screening participation (DRS > 25). A good global quality of life was reported in participants with no cancer.
Conclusion
Some psychological distress remains up to 6 months after colonoscopy in participants who tested false‐positive in the Dutch bowel cancer screening program.
After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme ...of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial.
The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4–8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5–3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001.
6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0–10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65–69) for the exemestane group and 67% (65–69) for the sequential group (hazard ratio 0·96, 0·88–1·05; p=0·39).
The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible.
Pfizer, Dutch Cancer Foundation.
Background
The aim was to study the impact of comorbidities and age on breast cancer mortality, taking into account competing causes of death.
Subjects, Materials, and Methods
Cohort analysis of ...Dutch and Belgian patients with postmenopausal, early hormone receptor‐positive breast cancer included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. This is a randomized controlled trial of patients who had completed local treatment with curative intent and were randomized to receive exemestane for 5 years, or sequential treatment of tamoxifen followed by exemestane for a duration of 5 years. Patients were categorized by number of comorbidities (no comorbidities, 1–2 comorbidities, and >2 comorbidities) and age (<70 years and ≥70 years). Main outcome was breast cancer mortality considering other‐cause mortality as competing event; cumulative incidences were calculated using the Cumulative Incidence Competing Risk Methods, and the Fine and Gray model was used to calculate the effect of age and comorbidities for the cause‐specific incidences of breast cancer death, taking into account the effect of competing causes of death.
Results
Overall, 3,159 patients were included, of which 2,203 (69.7%) were aged <70 years and 956 (30.3%) were aged ≥70 years at diagnosis. Cumulative incidence of breast cancer mortality was higher among patients ≥70 without comorbidities (22.2%, 95% CI, 17.5–26.9) compared with patients <70 without comorbidities (15.6%, 95% CI, 13.6–17.7, reference group), multivariable subdistribution hazard ratio (sHR) 1.49 (95% CI, 1.12–1.97, p = .005) after a median follow‐up of 10 years. Use of chemotherapy was lower in older patients (1%, irrespective of the number of comorbidities) compared with younger patients (50%, 44%, and 38% for patients with no, 1–2, or >2 comorbidities, p < .001).
Conclusion
Older patients without comorbidities have a higher risk of dying due to breast cancer than younger counterparts, even when taking into account higher competing mortality, while use of chemotherapy in this group was low. These findings underline the need to take into account comorbidities, age, and competing mortality in the prognosis of breast cancer for accurate decision making.
Implications for Practice
Older patients without comorbidity are at increased risk of dying from breast cancer, despite a higher other‐cause mortality. This study shows that including age and comorbidity for the assessment of breast cancer mortality and other‐cause mortality is indispensable for treatment decision making in older patients. Future prognostic tools for breast cancer prognosis should incorporate these items as well as risk of toxicity of adjuvant chemotherapy to adequately predict outcomes to optimize personalized treatment for older patients with early breast cancer.
This analysis of TEAM trial data focuses on the effects of comorbidities and age on breast cancer mortality and other cause mortality after 10 years of follow‐up, taking into account competing causes of death.
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