Age-friendly healthcare: integrating the 4Ms to enable age-friendly cancer care.

PURPOSE OF REVIEW: There is a growing movement towards person-centred, age-friendly healthcare in the care of older adults, including those with cancer. The Age-Friendly Health Systems (AFHS) initiative uses the 4Ms framework to enable this change. This review documents the utility and implications of 4Ms implementation across different settings, with a particular focus on cancer care. RECENT FINDINGS: The AFHS initiative 4Ms framework uses a set of core, evidence-based guidelines (focussing on What Matters, Medication, Mentation and Mobility) to improve person-centred care. The successful implementation of the 4Ms has been documented in many different healthcare settings including orthopaedics primary care, and cancer care. Implementation of the 4Ms framework into existing workflows complements the use of geriatric assessment to improve care of older adults with cancer. Models for implementation of the 4Ms within a cancer centre are described. Active engagement and education of healthcare providers is integral to success. Solutions to implementing the What Matters component are addressed. SUMMARY: Cancer centres can successfully implement the 4Ms framework into existing workflows through a complex change management process and development of infrastructure that engages healthcare providers, facilitating cultural change whilst employing quality improvement methodology to gradually adapt the status quo to age-friendly processes.

Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older.

BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

Durability of response to immune checkpoint inhibitors in metastatic Merkel cell carcinoma after treatment cessation.

BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is highly responsive to immune checkpoint inhibitors (ICIs); however, durability of response after treatment cessation and response to retreatment in the setting of progression is unknown. METHODS: Patients (pts) having mMCC from 10 centres who discontinued ICI treatment for a reason other than progression were studied. RESULTS: Forty patients were included. Median time on treatment was 13.5 months (range 1-35). Thirty-one patients (77.5%) stopped treatment electively while 9 patients (22.5%) stopped due to treatment-related toxicity. After median of 12.3 months from discontinuation, 14 pts (35%) have progressed (PD). Disease progression rate following ICI discontinuation was 26% (8 of 31) in patients who discontinued in complete response (CR), 57% (4 of 7) in patients in partial response and 100% (2 of 2) in those with stable disease. Median progression-free survival (PFS) after treatment cessation was 21 months (95% confidence interval [CI], 18- not reached [NR]), with a third of patients progressing during their first year off treatment. PFS was longer for patients who discontinued ICI electively (median PFS 29 months; 95% CI, 21-NR) compared to those who stopped due to toxicity (median PFS 11 months; 95% CI, 10-NR). ICI was restarted in 8 of 14 pts (57%) with PD, with response rate of 75% (4 CR, 2 partial response, 1 stable disease, 1 PD). CONCLUSION: ICI responses in mMCC do not appear durable off treatment, including in patients who achieve a CR, though response to retreatment is promising. Extended duration of treatment needs to be investigated to optimise long-term outcomes.

Perioperative Beta-Blocker Supply and Survival in Women With Epithelial Ovarian Cancer and a History of Cardiovascular Conditions.

PURPOSE: Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study. MATERIALS AND METHODS: Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects. RESULTS: Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery. CONCLUSION: Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.

Exercise as a supportive care strategy in men with prostate cancer receiving androgen deprivation therapy at a regional cancer centre: a survey of patients and clinicians.

PURPOSE: To understand how frequently exercise is discussed and/or prescribed as a supportive care measure and the barriers and facilitators to exercise uptake for men with prostate cancer receiving androgen deprivation therapy (ADT) at a regional cancer centre. METHODS: An observational, cross-sectional study was conducted at a regional cancer centre in three stages: (1) Retrospective chart review of men with prostate cancer undergoing ADT to identify the frequency of discussion and/or prescription of supportive care measures; (2) prospective patient survey exploring barriers and facilitators to exercise; and (3) prospective clinician survey exploring barriers, facilitators and awareness of exercise guidelines in men with prostate cancer. RESULTS: Files of 100 men receiving ADT (mean age 73 years; mean ADT duration =12 months) in the medical oncology (n = 50) and radiation oncology (n = 50) clinics were reviewed. Exercise was discussed with 16% of patients and prescribed directly to 5%. Patient survey (n = 49). 44.2% of patients reported participating in exercise at a high level. Common barriers to exercise participation included fatigue (51.0%), cancer/treatment-related weakness (46.9%) and joint stiffness (44.9%). 36.7% of patients reported interest in a supervised exercise program. Clinician survey (n = 22). 36.4% identified one or more exercise guidelines, and 40.9% correctly identified national exercise guidelines. Clinicians reported low knowledge of referral pathways to a supervised exercise program (27.3%). Clinicians believe physiotherapists (95.5%) are most suited to exercise prescription and 72.7% stated that exercise counselling should be part of supportive care. Limited time (63.6%) and patient safety (59.1%) were the two most common barriers to discussing exercise with patients. Clinicians reported that only 21.9% of their patients asked about exercise. The most endorsed facilitators to increase exercise uptake were patient handouts (90.9%) and integration of exercise specialists into the clinical team (86.4%). CONCLUSION: Despite a third of patient respondents indicating an interest in a supervised exercise program, only 16% of patients with prostate cancer undergoing ADT at a regional cancer centre engaged in a discussion about exercise with their treating clinicians. Physical limitations and fatigue were the greatest barriers for patients. Clinicians indicated a need for more clinician education and better integration of exercise specialists into clinical care. A tailored, integrated approach is needed to improve the uptake of exercise in men with prostate cancer.

Targeted Therapies in the Management of Ovarian Cancer: A Focus on Older Patients.

Ovarian cancer is one of the most common gynaecological malignancies and one of the leading causes of cancer mortality in women. The standard of care for ovarian cancer is maximal de-bulking surgery followed by adjuvant platinum-based chemotherapy. The median age at diagnosis is 63 years, yet older patients are under-represented in clinical trials. Historically, 65 years of age has been used as a definition of elderly; however, such an age cut-off encompasses a highly heterogeneous population with regards to comorbidity, functional status, and cognition. New targeted therapies are emerging in the treatment of ovarian cancer, with the most experience being with bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors. These agents have led to significant improvements in progression-free survival in selected trial populations. Whilst evidence for the use of these agents in older women is limited, there appears to be no signal for any difference in efficacy. The potential risk of increased toxicity in older adults with comorbidities is explored using the data available. More evidence is needed in the application of newer targeted therapies in older women with ovarian cancer, and improved accrual of older patients to clinical trials is required.

Supportive Care in Older Adults with Cancer: Across the Continuum.

Supportive care is an essential component of anticancer treatment regardless of age or treatment intent. As the number of older adults with cancer increases, and supportive care strategies enable more patients to undergo treatment, greater numbers of older patients will become cancer survivors. These patients may have lingering adverse effects from treatment and will need continued supportive care interventions. Older adults with cancer benefit from geriatric assessment (GA)-guided supportive care interventions. This can occur at any stage across the cancer treatment continuum. As a GA commonly uncovers issues potentially unrelated to anticancer treatment, it could be argued that the assessment is essentially a supportive care strategy. Key aspects of a GA include identification of comorbidities, assessing for polypharmacy, screening for cognitive impairment and delirium, assessing functional status, and screening for psychosocial issues. Treatment-related issues of particular importance in older adults include recognition of increased bone marrow toxicity, management of nausea and vomiting, identification of anemia, and prevention of neurotoxicity. The role of physical therapy and cancer rehabilitation as a supportive care strategy in older adults is important regardless of treatment stage or intent.

Supportive care in older adults with cancer - An update of research in 2015.

The motto of the Multinational Association for Supportive Care in Cancer (MASCC) is "supportive care makes excellent cancer care possible". This is especially important in the care of older adults with cancer. The use of geriatric assessment in this patient population enables targeted supportive care interventions to work alongside appropriate anticancer therapy. It is the opinion of this author that geriatric oncology is mostly about the provision of streamlined, appropriate supportive care. There are many facets of supportive care of patients with cancer that are important regardless of age. These include issues such as the use of appropriate antiemetics, infection management, oral health, nutritional intervention, psychosocial care, and palliative care. This article provides an update on novel yet important supportive care research specifically in older adults with cancer published in peer-reviewed journals in 2015. This year saw important publications in geriatric assessment, psychosocial care, in the information and supportive care needs of older adults and the role of pharmacists and rehabilitation specialists in the geriatric oncology clinic.

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

OBJECTIVE: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. MATERIAL AND METHODS: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. RESULTS: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. CONCLUSION: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.

Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study.

PURPOSE: This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy. PATIENTS AND METHODS: Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients. RESULTS: Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm. CONCLUSION: Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.

WITHDRAWN: Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain. OBJECTIVES: To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information. MAIN RESULTS: Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity. AUTHORS' CONCLUSIONS: Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.

Chemotherapy for ovarian cancer in the older adult.

The treatment of epithelial ovarian cancer in the older adult presents many challenges. The standard of care is cytoreductive surgery with the aim of achieving minimal residual disease. Surgery is then usually followed by six cycles of platinum-taxane chemotherapy. Older patients often have comorbidities which limit treatment choice and increase the risk of major surgical procedures. Platinum-based chemotherapy is generally well tolerated in fit elderly patients but can result in more toxicity in patients of increasing age. Results of a recent randomized trial of neoadjuvant platinum-based chemotherapy vs upfront surgery reveal decreased toxicity and equivalent survival in patients who receive chemotherapy prior to surgery. Treatment strategies to reduce the toxicity of chemotherapy include the use of single agent carboplatin, dose reduction, and weekly scheduling. Comprehensive geriatric assessment (CGA) of older patients prior to treatment may predict for toxicity of therapy and even survival. While comprehensive assessment may be desirable, it is impractical in the clinic. A simplified screening tool to detect geriatric problems and the further need for a formal assessment is more feasible. Prospective clinical trials of therapy in the elderly patient population are needed to guide treatment decisions.

Sentinel node biopsy: an in depth appraisal.

Sentinel node biopsy (SNB) in primary breast cancer has been taken-up widely to avoid the morbidity attributable to axillary node clearance (ANC). Currently many issues surrounding SNB are undecided. This review summarises why some form of axillary surgery is required and presents data on all aspects of SNB including methodology, clinical results and problems that may delay the introduction of SNB as best practice for all patients with primary breast cancer. There is no long or medium term data relating to the consequences of replacing ANC with SNB, but the mechanisms and probable magnitude of both beneficial and detrimental effects are estimated. A low level of false negative results are inherent to the technique but it is demonstrated that SNB is likely to have an only marginal (0.6%) effect on survival that would be undetectable by clinical trials. Patient sub-groups particularly likely to benefit from SNB are identified.

Gastro-oesophageal complications in patients receiving cancer therapy: the role of proton pump inhibitors.

Chemotherapy and radiotherapy, both alone and in combination, remain important tools in the successful treatment of cancer. Because the oral and gastrointestinal (GI) mucosa is often significantly damaged by cancer therapy, management of these problems is an important challenge for oncologists. Such treatment complications are generally not severe or life threatening, but they can result in both treatment delays and dose reductions in potentially curative regimens. Numerous therapeutic approaches have been evaluated as prophylaxis or treatment for mucosal damage in patients undergoing cancer therapy. The results of large-scale, placebo-controlled, comparative trials demonstrate that administration of a proton pump inhibitor (PPI) can provide both significant symptom relief and prophylaxis against upper GI ulceration in patients receiving cancer chemotherapy. Although no corresponding clinical trial has been conducted in patients undergoing irradiation, PPIs are also likely to be effective in preventing gastro-oesophageal mucosal injury in such individuals. Thus, PPIs may play a crucial role in supportive care for patients undergoing cancer therapy.