Epidemiology of Cancer in Older Adults: A Systematic Review.

PURPOSE OF REVIEW: What are the prevalence, incidence and mortality rates of cancer among individuals aged 60 or older on a national, regional, and global scale? What factors affect differences in cancer survival between older and younger adults? RECENT FINDINGS: The epidemiological literature on cancer in older adults, particularly in low- and middle-income countries (LMICs) and that focusing on the oldest adults, is expanding. These studies consistently show increasing global cancer incidence rates in older populations. Recent research also highlights a widening survival gap between middle-aged and older adults, with the stage at diagnosis being the primary driver. More research is needed to describe the cancer burden in older adults, especially focusing on the oldest population and LMICs, to better understand global healthcare challenges. Additionally, further exploring patient-related, clinical, and tumour-related factors which drive age-related survival differences could improve cancer outcomes in older adults.

Frequency of use and characterization of frailty assessments in observational studies on older women with breast cancer: a systematic review.

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.

Persistent High Long-term Excess Mortality After Elective AAA Repair Especially in Women: A Large Population-based Study.

OBJECTIVE: The aim of this time-trend analysis is to estimate long-term excess mortality and associated cardiovascular risk for abdominal aortic aneurysm (AAA) patients after elective repair while addressing the changes in AAA management and patient selection over time. BACKGROUND: Despite the intensification of endovascular aneurysm repair and cardiovascular risk management, Swedish population data suggest that AAA patients retain a persistently high long-term mortality after elective repair. The question is whether this reflects suboptimal treatment, a changing patient population over time, or a national phenomenon. METHODS: Nationwide time-trend analysis including 40,730 patients (87% men) following elective AAA repair between 1995 and 2017. Three timeframes were compared, each reflecting changes in the use of endovascular aneurysm repair and intensification of cardiovascular risk management. Relative survival analyses were used to estimate disease-specific excess mortality. Competing risk of death analysis evaluated the risk of cardiovascular versus noncardiovascular death. Sensitivity analysis evaluated the impact of changes in patient selection over time. RESULTS: Short-term excess mortality significantly improved over time. Long-term excess mortality remained high with a doubled mortality risk for women (relative excess risk=1.87, 95% CI: 1.73-2.02). Excess mortality did not differ between age categories. The risk of cardiovascular versus noncardiovascular death remained similar over time, with a higher risk of cardiovascular death for women. Changes in patient population (ie, older and more comorbid patients in the latter period) marginally impacted excess mortality (2%). CONCLUSIONS: Despite changes in AAA care, patients retain a high long-term excess mortality after elective repair with a persistent high cardiovascular mortality risk. In this, a clear sex - but no age - disparity stands out.

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

BACKGROUND: A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. METHODS: Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. RESULTS: A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. DISCUSSION: Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.

Excess Mortality for Abdominal Aortic Aneurysms and the Potential of Strict Implementation of Cardiovascular Risk Management: A Multifaceted Study Integrating Meta-Analysis, National Registry, and PHAST and TEDY Trial Data.

OBJECTIVE: Previous studies imply a profound residual mortality risk following successful abdominal aorta aneurysm (AAA) repair. This excess mortality is generally attributed to increased cardiovascular risk. The aim of this study was (1) to quantify the excess residual mortality for patients with AAA, (2) to evaluate the cross sectional level of cardiovascular risk management, and (3) to estimate the potential of optimised cardiovascular risk management to reduce the excess mortality in these patients. METHODS: Excess mortality was estimated through a systematic review and meta-analysis, and through data from the Swedish National Health Registry. Cardiovascular risk profiles were individually assessed during eligibility screening of patients with AAA for two multicentre pharmaceutical AAA stabilisation trials. The potential of full implementation of cardiovascular risk management was estimated through the validated Second Manifestations of ARTerial disease (SMART) risk scores algorithm. RESULTS: The meta-analysis showed a similarly impaired survival for patients who received early repair (small AAA) or regular repair (≥ 55 mm), and a further impaired survival for patients under surveillance for a small AAA. Excess mortality was further quantified using Swedish population data. The data revealed a more than quadrupled and doubled five year mortality rate for women and men who had their AAA repaired, respectively. Evaluation of the level of risk management of 358 patients under surveillance in 16 Dutch hospitals showed that the majority of patients with AAA did not meet therapeutic targets set for risk management in high risk populations, and indicated a more pronounced prevention gap in women. Application of the SMART risk score algorithm predicted that optimal implementation of risk management guidelines would reduce the 10 year risk of major adverse cardiovascular events from 43% to 14%. CONCLUSION: Independent of the rupture risk, AAA is associated with a worryingly compromised life expectancy with a particularly poor prognosis for women. Optimal implementation of cardiovascular risk prevention guidelines is predicted to profoundly reduce cardiovascular risk.

Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Statin use is associated with a reduced risk of developing colorectal cancer with intact SMAD4 expression.

Follow-up Schedule for Patients With Sentinel Node-negative Cutaneous Melanoma (The MELFO Study): An International Phase III Randomized Clinical Trial.

OBJECTIVES AND DESIGN: The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines. BACKGROUND: Evidence-based guidelines for the follow-up of sentinel node-negative melanoma patients are lacking. METHODS: Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared. RESULTS: At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54-1.39, P =0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P =0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49-2.07, P =0.99). CONCLUSIONS: A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node-negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients' acceptance is very high.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer.

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.

Visceral adipose tissue is a better predictor than BMI in the alternative Fistula Risk Score in patients undergoing pancreatoduodenectomy.

BACKGROUND: Muscle attenuation (MA) and visceral adipose tissue (VAT) have not yet been included in the currently used alternative Fistula Risk Score (a-FRS). The aim of this study was to examine the added value of these parameters as predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in the a-FRS after pancreatoduodenectomy compared to Body Mass Index (BMI). METHODS: A single center retrospective cohort study was performed in patients who underwent pancreatoduodenectomy between 2009 and 2018. The a-FRS model was reproduced, MA and VAT were both combined and separately added to the model instead of BMI using logistic regression analysis. Model discrimination was assessed by ROC-curves. RESULTS: In total, 329 patients were included of which 55 (16.7%) developed CR-POPF. The a-FRS model showed an AUC of 0.74 (95%CI: 0.68-0.80). In this model, BMI was not significantly associated with CR-POPF (p = 0.16). The MA + VAT model showed an AUC of 0.81 (95%CI: 0.75-0.86). VAT was significantly associated with CR-POPF (per cm2, OR: 1.01; 95%CI: 1.00-1.01; p < 0.001). The AUC of the MA + VAT model differed significantly from the AUC of the a-FRS model (p = 0.001). CONCLUSION: Visceral adipose tissue is of added value in the a-FRS compared to BMI in predicting CR-POPF in patients undergoing pancreatoduodenectomy.

Watch and wait after a clinical complete response in rectal cancer patients younger than 50 years.

BACKGROUND: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait. METHODS: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD). RESULTS: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998). CONCLUSION: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment.

Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB.

BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics have prognostic value in clinical stage IB-II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB-II melanoma. METHODS: Prospectively recorded data of patients with clinical stage IB-II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox-regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow-thickness, ulceration, mitotic rate, SLN-status) and patient-related variables (gender, age, and social-economic-status [SES]) and disease-free interval (DFI), melanoma-specific survival (MSS), and overall survival (OS). RESULTS: Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6-89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98-2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97-2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85-1.85; p = 0.25). Increased age, arm location, increased Breslow-thickness, ulceration, increased mitotic rate, and positive SLN-status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated. CONCLUSION: Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB-II melanoma who underwent SLNB.

Differences in organization of care are associated with mortality, severe complication and failure to rescue in emergency colon cancer surgery.

BACKGROUND: Emergency colon cancer surgery is associated with increased mortality and complication risk, which can be due to differences in the organization of hospital care. This study aimed. OBJECTIVE: To explore which structural factors in the preoperative, perioperative and postoperative periods influence outcomes after emergency colon cancer surgery. METHODS: An observational study was performed in 30 Dutch hospitals. Medical records from 1738 patients operated in the period 2012 till 2015 were reviewed on the type of referral, intensive care unit (ICU) level, surgeon specialization and experience, duration of surgery and operating room time, blood loss, stay on specialized postoperative ward, complication occurrence, reintervention and day of surgery and linked to case-mix data available in the Dutch Colorectal Audit. Multivariate logistic regression analysis was used to estimate the influence of these factors on 30-day mortality, severe complication and failure to rescue (FTR), after adjustment for case-mix. RESULTS: Patients operated by a non-Gastro intestinal/oncology specialized surgeon have significantly increased mortality (Odds Ratio (OR) 2.28 [95% confidence interval (95% CI) 1.23-4.23]) and severe complication risk (OR 1.61 [95% CI 1.08-2.39]). Also, duration of stay in the operating room was significantly associated with increased risk on severe complication (OR 1.03 [95% CI 1.01-1.06]). Patients admitted to a non-specialized ward have significantly increased mortality (OR 2.25 [95% CI 1.46-3.47]) and FTR risk (OR 2.39 [95% CI 1.52-3.75]). A low ICU level (basic ICU) was associated with a lower severe complication risk (OR 0.72 [95% CI 0.52-1.00]). Surgery on Tuesday was associated with a higher mortality risk (OR 2.82 [95% CI 1.24-6.40]) and a severe complication risk (OR 1.77, [95% CI 1.19-2.65]). CONCLUSION: This study identified a non-specialized surgeon and ward, operating room, time and day of surgery to be risk factors for worse outcomes in emergency colon cancer surgery.

Long-term Prognosis After Elective Abdominal Aortic Aneurysm Repair is Poor in Women and Men: The Challenges Remain.

OBJECTIVE: To evaluate the impact of changes in elective Abdominal Aortic Aneurysm (AAA) management on life-expectancy of AAA patients. BACKGROUND: Over the past decades AAA repair underwent substantial changes, that is, the introduction of EVAR and implementation of intensified cardiovascular risk management. The question rises to what extent these changes improved longevity of AAA patients. METHODS: National evaluation including all 12.907 (82.7% male) patients who underwent elective AAA repair between 2001 and 2015 in Sweden. The impact of changes in AAA management was established by a time-resolved analysis based on 3 timeframes: open repair dominated period (2001-2004, n = 2483), transition period (2005-2011, n = 6230), and EVAR-first strategy period (2012-2015, n = 4194). Relative survival was used to quantify AAA-associated mortality, and to adjust for changes in life-expectancy. RESULTS: Relative survival of electively treated AAA patients was stable and persistently compromised [4-year relative survival and 95% confidence interval: 0.87 (0.85-0.89), 0.87 (0.86-0.88), 0.89 (0.86-0.91) for the 3 periods, respectively]. Particularly alarming is the severely compromised survival of female patients (4-year relative survival females 0.78, 0.80, 0.70 vs males 0.89, 0.89, 0.91, respectively). Cardiovascular mortality remained the main cause of death (51.0%, 47.2%, 47.9%) and the proportion cardiovascular disease over non-cardiovascular disease death was stable over time. CONCLUSIONS: Changes in elective AAA management reduced short-term mortality, but failed to improve the profound long-term survival disadvantage of AAA patients. The persistent high (cardiovascular) mortality calls for further intensification of cardiovascular risk management, and a critical appraisal of the basis for the excess mortality of AAA patients.

Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

BACKGROUND: Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account. MATERIALS AND METHODS: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70-74 [reference group], 75-79, and ≥80 years) on recurrence risk. RESULTS: A total of 18,419 patients were included. Nine-year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70-74, 75-79, and ≥80 years, and 9-year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75-79 years remained at higher risk after adjustment for tumor and treatment characteristics (75-79 years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11-1.41; ≥80 years sHR, 1.03; 95% CI, 0.91-1.17). CONCLUSION: Patients aged 75-79 years had a higher risk of distant recurrence than patients aged 70-74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer. IMPLICATIONS FOR PRACTICE: In this population-based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75-79 years were at higher risk of distant recurrence than were patients aged 70-74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy.

The effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma.

OBJECTIVE: The subset distribution and immunophenotype of circulating immune cells ("peripheral blood immune cell profile") may reflect tumor development and response to cancer treatment. In order to use the peripheral blood immune cell profile as biomarker to monitor patients over time, it is crucial to know how immune cell subsets respond to therapeutic interventions. In this study, we investigated the effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma (CC). METHODS: The subset distribution and immunophenotype of T cells (CD3+CD56-), CD56dim NK cells (CD3-CD56dim), CD56bright NK cells (CD3-CD56bright) and NKT-like cells (CD3+CD56+) were studied in preoperative and postoperative peripheral blood mononuclear cell (PBMC) samples of 24 patients with CC by multiparameter flow cytometry. Changes in immunophenotype of circulating immune cells after tumor resection were studied in patients treated with and without (capecitabine-based) adjuvant therapy. RESULTS: The NKT-like cell (% of total PBMCs) and CD8+ T cell (% of total T cells) populations expanded in the peripheral blood of non-adjuvant-treated CC patients after surgery. NK- and NKT-like cells showed upregulation of activating receptors and downregulation of inhibitory receptors in non-adjuvant-treated CC patients after surgery. These changes were not observed in the peripheral blood of adjuvant-treated CC patients. CONCLUSIONS: Our results suggest tumor-induced suppression of NK- and NKT-like cells in CC patients, an effect that could not be detected after tumor resection. In contrast, adjuvant therapy maintained tumor-induced immunosuppression of NK- and NKT-like cells in CC patients.

Early stage breast cancer treatment and outcome of older patients treated in an oncogeriatric care and a standard care setting: an international comparison.

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.

The intra-tumoural stroma in patients with breast cancer increases with age.

PURPOSE: The tumour microenvironment in older patients is subject to changes. The tumour-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥ 70 years). METHODS: Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on haematoxylin and eosin stained tissue slides. RESULTS: The intra-tumoural stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, p = 0.016 and B 0.034, 95% CI 0.015-0.054, p < 0.001, respectively). Fifty-one per cent of the patients from the Nottingham Breast Cancer series < 40 years had a stroma-high tumour compared to 73% of the patients of ≥ 90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years. CONCLUSIONS: The intra-tumoural stroma increases with age. This might be the result of an activated tumour microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years in contrast to young women with breast cancer as published previously.

The MELFO Study: A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB-IIC Patients-Results After 3 Years.

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.

The MelFo Study UK: Effects of a Reduced-Frequency, Stage-Adjusted Follow-Up Schedule for Cutaneous Melanoma 1B to 2C Patients After 3-Years.

BACKGROUND: Evidence-based guidelines for follow-up treatment of American Joint Committee on Cancer (AJCC) stages 1B to 2C melanoma patients are lacking. The MELanoma FOllow-up study is an international phase 3 randomized trial, and the 3-year interim data were recently reported from the Netherlands. The study was undertaken concurrently with a British cohort for comparison and validation of the Dutch study. METHODS: The study enrolled and stratified 207 patients by AJCC stage. The conventional schedule group (CSG; n = 103) cohort was reviewed as per UK guidelines. The experimental schedule group (ESG; n = 104) cohort was reviewed in a reduced-frequency nurse-led, consultant-supervised clinic. Quality of life (QoL) was measured at baseline (T1), a 1 year (T2), and at 3 years (T3) using the State-Trait Anxiety Inventory, the Cancer Worry Scale, the Impact-of-Event Scale, and the Mental and Physical Component scales (PCS/MCS) of the RAND-36. RESULTS: Of the 207 QoL questionnaires, 170 (82.1%) were completed at T3. Both cohorts expressed high satisfaction (> 93%) with their regimens. At T3, no significant group effect was found on any patient-reported outcome measures scores, indicating no QoL difference between the follow-up protocols. Recurrence had developed in 33 patients Conventional follow-up (CFU), 16 [15.5%]; Experimental follow-up (EFU), 17 [16.3%]. Self-examination was the method of detection for 12 ESG patients (70.6%) and 11 CSG patients (68.8%). The melanoma-specific survival was identical. CONCLUSION: The UK 3-year data were consistent with the previous Dutch report. The reduced follow-up strategy was shown to be safe, with significant resource usage benefits for national cancer services. Patient anxiety levels were not increased by a less-intensive follow-up regimen, and acceptance was high. The study data indicate that patient self-examination is very effective for recurrence detection.

Treatment and Survival of Elderly Patients with Stage I-II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium.

BACKGROUND: Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. OBJECTIVE: The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I-II pancreatic cancer in the EURECCA Pancreas Consortium. METHODS: This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. RESULTS: In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. CONCLUSIONS: Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I-II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment.