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.
Background
This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a ...stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs.
Methods
Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB–IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG,
n
= 93) or experimental (ESG,
n
= 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory–State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales PCS/MCS). Three years later (T3), 110 patients (CSG,
n
= 56; ESG,
n
= 54) completed PROMs, while 42 declined (23%).
Results
Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (
p
= 0.001) in favor of the ESG, and on the RAND-36 PCS (
p
= 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio HR 0.71 0.32–1.58;
p
= 0.400) and disease-free survival (HR 1.24 0.42–3.71;
p
= 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG.
Conclusion
These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB–IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline.
Frail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated the effect of ...physical prehabilitation on postoperative complications in a retrospective cohort of frail CRC patients.
The study consisted of all consecutive non-metastatic CRC patients ≥70 years who had elective surgery from 2014 to 2019 in a teaching hospital in the Netherlands, where a physical prehabilitation program was implemented from 2014 on. We performed both an intention-to-treat and per protocol analysis to evaluate postoperative complications in the physical prehabilitation (PhP) and non-prehabilitation (NP) group.
Eventually, 334 elective patients were included. The 124 (37.1%) patients in the PhP-group presented with higher age, higher comorbidity scores and walking-aid use compared to the NP-group. Medical complications occurred in 26.6% of the PhP-group and in 20.5% of the NP-group (p = 0.20) and surgical complications in 19.4% and 14.3% (p = 0.22) respectively. In all frailty subgroups, the medical complications were lower in the PhP-group compared to the NP-group (35.9% vs. 45.5% for patients with ≥2 comorbidities, 36.2% vs. 39.1% for ASA score ≥ III, 29.2% vs. 45.8% for walking-aid use). Differences were not significant.
In this study, patients selected for physical prehabilitation had a worse frailty profile and therefore a higher a priori risk of postoperative complications. However, the postoperative complication rate was not increased compared to patients who were less frail at baseline and without prehabilitation. Hence, physical prehabilitation may prevent postoperative complications in frail CRC patients ≥70 years.
Abstract Background & Aims Statin use has been associated with a reduced incidence of colorectal cancer, and might also affect survival of patients diagnosed with colon cancer. Statins are believed ...to inhibit Ras signaling, and also activate the bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer, and whether their effects were associated with changes in KRAS or the BMP signaling pathways. Methods Data were derived from the PHARMO database network (Netherlands) and linked to patients diagnosed with colon cancer from 2002 through 2007, listed in the Eindhoven Cancer Registry. We obtained information on causes of death from statistics Netherlands. We constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008. Survival was analyzed with statin user status after diagnosis as a time-dependent covariate. Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival. Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4, BMPR1A, BMPR1B, and BMPR2 proteins. Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A, BMPR1B, or BMPR2. DNA was isolated from tumor tissues and analyzed by quantitative PCR to detect mutations in KRAS. The primary outcome measures were overall mortality and cancer-specific mortality. Results In this cohort, 21.0% of the patients (210/999) were defined as statin users after colon cancer diagnosis. Statin use after diagnosis was significantly associated with reduced risk of death from any cause (adjusted relative risk RR, 0.67; 95% CI, 0.51–0.87; P=.003) and death from cancer (adjusted RR, 0.66; 95% CI, 0.49-0.89; P=.007). Statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling (adjusted RR, 0.39; 95% CI, 0.22–0.68; P=.001), but not for patients whose tumors did not have BMP signaling (adjusted RR, 0.81; 95% CI, 0.55–1.21; P=0.106; P<.0001 for the interaction). Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations (adjusted RR, 0.81; 95% CI, 0.56–1.18; P=.273) or whose tumors did have KRAS mutations (adjusted RR, 0.59; 95% CI 0.35–1.03; P=.062; P for the interaction=0.90). Conclusions In an analysis of 999 patients with a diagnosis of colon cancer, we associated statin with reduced risk of death from any cause or from cancer. The benefit of statin use is greater for patients whose tumors have intact BMP signaling, independent of KRAS mutation status. Randomized controlled trials are required to confirm these results.
Abstract Background Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty ...assessments are utilized in observational research for the older breast cancer population is uncertain. Therefore, the aim of this review was to determine the frequency of use of frailty assessments in studies investigating survival or mortality, and characterize them, concentrating on literature from the past 5 years (2017–2022). Methods MEDLINE, EMBASE and Cochrane Library were systematically queried to identify observational studies (case-control, cohort, cross-sectional) published from 2017-2022 that focus on older females ( ≥ 65 years) diagnosed with breast cancer, and which evaluate survival or mortality outcomes. Independent reviewers assessed the studies for eligibility using Covidence software. Extracted data included characteristics of each study as well as information on study design, study population, frailty assessments, and related health status assessments. Risk of bias was evaluated using the appropriate JBI tool. Information was cleaned, classified, and tabulated into review level summaries. Results In total, 9823 studies were screened for inclusion. One-hundred and thirty studies were included in the final synthesis. Only 11 (8.5%) of these studies made use of a frailty assessment, of which 4 (3.1%) quantified frailty levels in their study population, at baseline. Characterization of frailty assessments demonstrated that there is a large variation in terms of frailty definitions and resulting patient classification (i.e., fit, pre-frail, frail). In the four studies that quantified frailty, the percentage of individuals classified as pre-frail and frail ranged from 18% to 29% and 0.7% to 21%, respectively. Identified frailty assessments included the Balducci score, the Geriatric 8 tool, the Adapted Searle Deficits Accumulation Frailty index, the Faurot Frailty index, and the Mian Deficits of Accumulation Frailty Index, among others. The Charlson Comorbidity Index was the most used alternative health status assessment, employed in 56.9% of all 130 studies. Surprisingly, 31.5% of all studies did not make use of any health status assessments. Conclusion Few observational studies examining mortality or survival outcomes in older women with breast cancer incorporate frailty assessments. Additionally, there is significant variation in definitions of frailty and classification of patients. While comorbidity assessments were more frequently included, the pivotal role of frailty for patient-centered decision-making in clinical practice, especially regarding treatment effectiveness and tolerance, necessitates more deliberate attention. Addressing this oversight more explicitly could enhance our ability to interpret observational research in older cancer patients.
Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have ...previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin use and the risk of developing colorectal cancer of a particular molecular subtype.
By linking two registries unique to the Netherlands, 69,272 statin users and 94,753 controls were identified and, if they developed colorectal cancer, their specimens traced. Colorectal cancers were molecularly subtyped according to the expression of SMAD4 and the mutation status of KRAS and BRAF.
Statin use was associated with a reduction in the risk of developing colorectal cancer regardless of molecular subtype (HR 0.77; 95% CI 0.66-0.89) and a larger reduction in the risk of developing SMAD4-positive colorectal cancer (OR 0.64; 95% CI 0.42-0.82). There was no relationship between statin use and the risk of developing colorectal cancer with a mutation in KRAS and/or BRAF.
Statin use is associated with a reduced risk of developing colorectal cancer with intact SMAD4 expression.
Purpose
Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of ...adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL).
Methods
Patients aged ≥ 70 years with stage I–III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time.
Results
Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (
b
= − 4.37; 95% CI − 7.96 to − 0.78;
p
= 0.017) over the first 2 years, in particular on the future perspective subscale (
b
= − 11.10; 95% CI − 18.80 to − 3.40;
p
= 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement.
Conclusion
A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.
Introduction
Since older patients with breast cancer are underrepresented in clinical trials, an oncogeriatric approach is advocated to guide treatment decisions. However, the effect on outcomes is ...unclear. The aim of this study was to compare treatments and outcomes between patients treated in an oncogeriatric and a standard care setting.
Methods
Patients aged ≥ 70 years with early stage breast cancer were included. The
oncogeriatric cohort
comprised unselected patients from the Moffitt Cancer Center, and the
standard cohort
patients from a Dutch population-based cohort. Cox models were used to characterize the influence of care setting on recurrence risk and overall mortality.
Results
Overall, 268 patients were included in the oncogeriatric and 1932 patients in the standard cohort. Patients in the oncogeriatric cohort were slightly younger, had more comorbidity, and received more adjuvant endocrine therapy and chemotherapy. Oncogeriatric care was associated with a lower risk of recurrence, which remained significant after adjustment for patient and tumour characteristics hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.44–0.99. Oncogeriatric care was also associated with a lower overall mortality, which also remained significant after adjustment for patient and tumour characteristics (HR 0.69, 95% CI 0.55–0.87).
Conclusions
Patients treated in the oncogeriatric care setting had a lower risk of recurrence, which may be explained by more systemic treatment. Overall mortality was also lower, but other explanations besides care setting could not be ruled out as the cohorts had different patient profiles. Future studies need to clarify the impact of an oncogeriatric approach on outcomes.
Survival trends help to evaluate the progress made to reduce the burden of cancer. The aim was to estimate the trends in 5-year relative survival of patients diagnosed with breast, prostate, lung, ...colorectal cancer and skin melanoma in the time periods 1980-1989, 1990-1999, 2000-2009 and 2010-2015 in the Canton of Zurich, Switzerland. Furthermore, we investigated relative survival differences by TNM stage and age group.
Data from the Cancer Registry of Zurich was used from 1980 to and including 2015, including incident cases of breast (N = 26,060), prostate (N= 23,858), colorectal (N= 19,305), lung cancer (N= 16,858) and skin melanoma (N= 9780) with follow-up until 31 December 2020. The cohort approach was used to estimate 5-year relative survival.
The 5-year relative survival increased significantly between 1980 and 1989, and 2010 and2015: from 0.70 to 0.89 for breast, from 0.60 to 0.92 for prostate, from 0.09 to 0.23 (men) and from 0.10 to 0.27 (women) for lung, from 0.46 to 0.66 (men) and from 0.48 to 0.68 (women) for colorectal cancer, and from 0.74 to 0.94 (men) and from 0.86 to 0.96 (women) for skin melanoma. Survival for stage IV tumors was considerably lower compared to lower-staged tumors for all cancer types. Furthermore, relative survival was similar for the age groups <80 years but lower for patients aged 80 years and older.
The observed increasing trends in survival are encouraging and likely reflect raised awareness around cancer, improved diagnostic methods, and improved treatments. The fact that stage I tumor patients have generally high relative survival reflects the efforts made regarding early detection.
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