Analysis of factors affecting progression-free survival of first-line chemotherapy in older patients with advanced gastrointestinal cancer

ObjectivesFew studies have investigated factors influencing the efficacy of chemotherapy in older patients with cancer. This study aimed to evaluate the usefulness of G8, geriatric assessment (GA), and factors measured in general clinical practice for evaluating progression-free survival (PFS) of first-line palliative chemotherapy in older patients with advanced gastrointestinal cancer.Materials and methodsThis was a prospective observational study of older patients (age ≥70 years) with advanced gastrointestinal cancer. The modified cut-off value of G8 was determined by referring to two or more abnormal GA conditions. The usefulness of baseline GA and G8 (conventional and modified cut-off value) was assessed according to the efficacy (PFS and disease control rate) of the administered first-line palliative chemotherapy.ResultsOverall, 93 patients were evaluated between March 2017 and February 2019. A modified G8 cut-off value of ≤12 had a sensitivity and specificity of 68.9% and 46.9%, respectively. PFS was significantly prolonged in the patients with G8 > 12, serum albumin ≥3.5 g/dl, and in whom grade ≥3 adverse events occurred. There was no significant difference in the PFS between monotherapy and combination therapy. GA was not useful for predicting PFS prolongation or the occurrence of serious adverse events in first-line treatment.ConclusionAmong older patients with advanced gastrointestinal cancer who receive first-line chemotherapy, a modified G8 cut-off value of 12 points, occurrence of grade 3 or higher adverse events, albumin levels, rather than age or performance status were predictors of PFS prolongation.     

Predictive value of geriatric oncology screening and geriatric assessment of older patients with cancer: A randomized clinical trial protocol (PROGNOSIS-RCT)

IntroductionComprehensive geriatric assessment (CGA) has been shown to reduce frailty in older patients in general. In older patients with cancer, frailty affects quality of life (QoL), physical function, and survival. However, few studies have examined the effect of CGA as an additional intervention to antineoplastic treatment. This protocol presents a randomized controlled trial, which aims to evaluate the effects of CGA-based interventions in older patients with cancer and Geriatric 8 (G8) identified frailty.Materials and MethodsThis randomized controlled trial will include patients, age 70+ years, with solid malignancies and G8 frailty (G8 ≤ 14). Patients will be separated into two groups, with different primary endpoints, depending on palliative or curative antineoplastic treatment initiation, and subsequently randomized 1:1 to either CGA with corresponding interventions or standard of care, along with standardized antineoplastic treatment.A geriatrician led CGA with corresponding interventions and clinical follow-up will be conducted within one month of antineoplastic treatment initiation. The interdisciplinary CGA will cover multiple geriatric domains and employ a standard set of validated assessment tools.Primary endpoints will be physical decline measured with the 30-s Chair-Stand-Test at three months (palliative setting) and unplanned hospital admissions at six months (curative setting). Additional outcomes include QoL, treatment toxicity and adherence, occurrence of polypharmacy, potential drug interactions, potential inappropriate medications, and survival. The primary outcomes will be analyzed using a mixed model regression analysis (30-s chair stand test) and linear regression models (unplanned hospitalizations), with an intention to treat approach. Power calculations reveal the need to enroll 134 (palliative) and 188 (curative) patients.DiscussionThe present study will examine whether CGA, as an additional intervention to antineoplastic treatment, can improve endpoints valued by older patients with cancer. Inclusion began November 2020 and is ongoing, with 37 and 29 patients recruited April 15th, 2021.Registration: NCT04686851     

Our experience of nursing/allied health practitioner led geriatric screening and assessment of older patients with cancer – a highly accessible model of care

ObjectiveComprehensive Geriatric Assessment (CGA) has been proven to assist development of tailored treatment plans for older patients with cancer by identifying health issues affecting their ability to complete systemic therapy or cope with and recover from cancer treatment.Materials and MethodsMetro North Hospital and Health Service (MNHHS) has significant older population with cancer. Geriatric Oncology services were commenced in February 2018 at two facilities of MNHHS [North Lakes Cancer Care Services/Caboolture Hospital (NLCCS/CBH) Cancer services and Redcliffe Hospital (RH) Cancer services]. The Geriatric 8 (G8) screening tool was administered to predict patient vulnerability and need for CGA. A bespoke CGA suite comprising of 16 assessments was used. A clinical nurse or Allied Health (AH) practitioner conducted screening, followed by CGA. Proposed care was discussed at multidisciplinary case conference and AH interventions were provided.ResultsFrom February’2018 to July’2019, the G8 was administered to 1380 patients between the two facilities (918 patients at NLCCS/CBH and 462 patients at RH), comprising oncology and haematology patients. 825 patients (59%) showed impairment on G8 and were recommended for CGA. Another 50 patients were referred for CGA as per clinical assessment despite normal G8. 65% (572) of recommended CGAs were conducted.The most common impairments identified on CGA leading to AH referrals were timed up & go >13 s, malnutrition, polypharmacy and low mood & depression.ConclusionThe nursing/AH practitioner led Geriatric Oncology service is feasible, applicable and beneficial to patients. Further study is planned to assess the impact of the service on patients' health related quality of life and chemotherapy completion rates.     

Exploring the geriatric needs of oncology inpatients at an academic cancer centre

PurposeGeriatric Assessments (GAs) in older adults with cancer have informed treatment decision-making and refined survival prediction. However, little is known about the needs of older inpatients with cancer. Our objectives were to test the feasibility of a bedside GA, assess the prevalence of impairments in geriatric domains, determine how many were unknown to the medical team, and assess the impact of GA on patient care.MethodsWe conducted a cross-sectional observational single-centre pilot study. Structured GAs were performed on patients age 65+ admitted to the medical or radiation oncology inpatient wards at a tertiary care cancer centre. GA findings were shared with the patient's most responsible physician (MRP).Results356 patients were screened, 39 were eligible and approached, and 37 were enrolled (recruitment rate 95%). Completion of the GA was possible in 92% of patients (34/37) and required a mean of 35 min. The mean number of geriatric domains impaired per patient was five (of seven assessed domains). The most common abnormal domains not known to the medical team were medication optimization (91%), cognition (90%), mood (69%), and social vulnerability (69%). MRPs responded to our survey for fifteen of thirty-three participants (45% response rate), and indicated that the GA results provided helpful information for patient management in 10 of 15 cases.ConclusionAbnormal geriatric domains are common in older inpatients with cancer. Domains such as medication optimization, cognition, mood, and social vulnerability often go undetected and unaddressed. Identifying abnormal domains may improve the care of older inpatients with cancer.     

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.     

Octogenarians treated for thoracic and lung cancers: Impact of comprehensive geriatric assessment

BackgroundLung cancer affects older and older old adults and is the leading cause of death by cancer. Comprehensive Geriatric Assessment (CGA) is recommended before and during cancer treatment to guide therapy management in this population.MethodsThis study was conducted between September 2015 and January 2019 at Marseille University Hospital (AP-HM). During this period, all consecutive outpatients 70 years or older referred for a CGA before initiation of lung cancer treatment were enrolled. The objective of this study was to compare lung and thoracic cancer management of octogenarians (≥80 years) and their geriatric profile versus patients aged 70 to 79 years (<80 years).FindingsIn our study, 228 patients were recruited. The median age was 78.7 ± 5 years. There were 94 octogenarians (41.2%), 36.2% of them were diagnosed with stage IV neoplasm and the most common treatment was chemotherapy (43.6%). The logistic regression analysis highlights that handgrip strength was the most commonly impaired domain (OR 2.3; 95% CI [1.3–4.3]) in octogenarians and that they are more likely than their younger counterparts to be treated by targeted therapy (OR 9.8; 95% CI [1.0–92.9]). Overall survival (OS) was similar in both age groups (log rank = 0,95).InterpretationIn our study, octogenarians and patients <80 years had equivalent survival, across the different thoracic cancer treatments and tumor stages. Measure of muscle strength in CGA could be very useful in a clinical setting to help improve the management of older old patients treated for lung or thoracic cancer.     

Remaining Agile in the COVID-19 pandemic healthcare landscape – How we adopted a hybrid telemedicine Geriatric Oncology care model in an academic tertiary cancer center

IntroductionThe COVID-19 pandemic has impacted healthcare on an unprecedented scale, with healthcare resources being channeled into managing the devastating effects of the outbreak. Healthcare provision for vulnerable older adults has also been affected by lockdowns and suspension of selected medical services worldwide. In our tertiary cancer center, the National University Cancer Institute, Singapore (NCIS), our Geriatric Oncology (GO) service for older adults with cancer was halted for five months. In this paper, we describe the adoption of a hybrid telemedicine model by our GO service to continue care provision for older adults in the midst of the pandemic.Materials and MethodsComprehensive geriatric assessments (CGA) were done via telemedicine and virtual multidisciplinary discussions were held prior to the patients' clinic visits. A hybrid telemedicine consultation allowed geriatricians and oncologists, segregated in different sites during the pandemic, to provide a hybrid physical and video geriatric oncology consultation. Scheduled phone follow ups by GO nurses helped to monitor patients for treatment-related toxicities and geriatric syndromes.ResultsTwo hundred fifty patients were enrolled in the program from July 2020 to August 2021. All were assessed with a CGA, with 240 receiving interventions in the one-stop clinic.The average amount of time spent per visit was shortened from four hours to two and a half hours with an average of three interventions on the same day, versus one previously.Of the patients who received interventions, 84.8% were satisfied with the hybrid telemedicine model and 80.8% of them had reported a maintained or improved quality of life after being enrolled in the program.DiscussionTelemedicine has been widely adopted during the pandemic, but older adults with limited digital literacy may find it a challenge. Our hybrid telemedicine model has allowed us to continue to provide cancer care, identify issues brought about by social isolation, and render timely assistance. It has become imperative to adapt, prepare and plan for the challenges we may face amid the ongoing COVID-19 pandemic and similar future outbreaks. Only by doing so can we remain agile and resilient, to continue providing quality care to our older patients with cancer.     

Validation of the G8 screening tool in older patients with cancer considered for surgical treatment

BackgroundThe Geriatric 8 (G8) has proven to be one of the most sensitive frailty-screening tools for older patients with cancer undergoing systemic treatment. In this study we validated whether the G8 is also suitable for identifying impairments in their comprehensive geriatric assessment (CGA) in older patients with cancer undergoing surgery. Thereby, we investigated the differences in postoperative outcomes between the fit and frail patients classified by the G8.MethodsPatients ≥70 years with a surgery indication because of a (suspected) malignant disease were prospectively enrolled. In all patients, a CGA was performed. The G8 results were assessed in parallel. The diagnostic value of the G8 was determined by comparing the result with the CGA as a reference test. Deficits in CGA was defined as ≥ two impairments of the CGA. Postoperative complications were retrospectively obtained from the medical record and compared between the fit and frail patients.ResultsIn total, 143 patients were enrolled. The sensitivity, specificity, and negative predictive value of the G8 were 82% (95% CI 70–91), 63% (95% CI 52–73), and 85% (95% CI 75–91). In the patients with an impaired G8, a significantly prolonged hospital stay, higher rate of delirium, and higher 1-year mortality rate were seen.ConclusionThe G8 is a simple and useful screening tool for identifying deficits in CGA in older patients with cancer requiring surgery. Second, we concluded that patients with an impaired G8 are more at risk for a complicated recovery from surgery.     

Second-line treatment efficacy and toxicity in older vs. non-older patients with advanced gastric cancer: A multicentre real-world study

ObjectivesAlthough gastric cancer (GC) incidence rises with age, older patients are poorly represented in clinical trials, whose results are therefore difficult to translate into standard management of older patients. Purpose of this study was to compare clinico-pathological features and survival outcomes between older and non-older patients with advanced GC treated with at least two chemotherapy lines.Materials and MethodsClinico-pathological characteristics, basal values, and treatment data of older (≥70 years at second-line start) and non-older patients were compared using chi-square test or 2-tailed Fisher exact test. The Kaplan-Meier estimation was used to calculate progression-free survival (PFS) and overall survival (OS), which were examined by log-rank test.ResultsOlder patients represented 31.8% of the population (N = 868). Intestinal type was more frequent in older patients (P = .02). Poorly differentiated tumours were more often observed in non-older patients (P = .009). At stage IV diagnosis, the rate of liver metastases was higher in older patients (P = .02), while peritoneal spread was more represented in non-older patients (P = .002). Although older patients were more often treated with monotherapy (P = .001), they had similar PFS (HR 0.86, 95%CI 0.71–1.03, P = .102) and OS (HR 0.82, 95%CI 0.65–1.02, P = .08) compared to the non-older counterpart. No statistical differences were observed in treatment-related adverse events, hospital admissions, or further treatment lines between age groups.ConclusionIn our large cohort study, despite some differences in tumour characteristics and treatment intensity, no survival difference was found between older and non-older patients with advanced GC treated with at least two chemotherapy lines. Incidence of adverse events was similar between age groups.     

The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people

Background:

Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer.

Methods:

Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010–July 2012) received standard oncology care. The intervention group (N=65, September 2011–February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions.

Results:

Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0–15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50–11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16–0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292).

Conclusions:

Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.     

The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO)

Background Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored.Methods The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL).Results Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008).Conclusion Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility.Trial registration ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT 02748811","term_id":"NCT02748811"}}NCT 02748811.Subject terms: Geriatrics, Colorectal cancer     

Chemotherapy use and survival in older adults with metastatic pancreatic cancer in the combination therapy era

BackgroundWhile a number of landmark clinical trials have led to the approval of combination chemotherapy regimens for metastatic pancreatic adenocarcinoma (mPC), older patients are underrepresented in these studies. We evaluated changes in practice patterns in the management of mPC among medical oncologists in the combination chemotherapy era (CCE).MethodsA retrospective analysis of patients treated at a tertiary cancer center between 2000 and 2015 was conducted. The cohort was divided into two groups (Pre-CCE, diagnosed with mPC between 2000 and 2009 and Post-CCE, diagnosed between 2010 and 2015). Fisher's exact test was used to compare categorical variables. Univariate (UVA) and multivariate analyses (MVA) were conducted to determine the impact of treatment and prognostic variables on survival.Results473 older patients with mPC were identified. Post-CCE, there were statistically significant increases in the use of chemotherapy (p < .005). While usage of gemcitabine was similar between groups, use of fluoropyrimidines, platinum, taxanes, and irinotecan increased Post-CCE. Use of chemotherapy conferred a modest but significant survival benefit (5 months Pre-CCE versus 6 months Post-CCE, p < .005). UVA and MVA showed significantly improved survival when older patients were treated with 2 or more chemotherapeutic agents.ConclusionsDespite the limited data available to guide clinicians on optimal usage of these treatments in older patients, medical oncology practice patterns for mPC have changed at an academic cancer center. Increases in chemotherapy use seems to confer a small survival benefit. Additional prospective data in older patients is necessary to improve our management of older patients with mPC.     

Subgroup analysis of older patients treated within the randomized phase 3 doxorubicin versus doxorubicin plus evofosfamide (SARC021) trial

BackgroundMore than half of patients with soft tissue sarcoma (STS) are aged ≥65 years (older), however contemporary data on the efficacy/safety of anthracycline chemotherapy in older patients with STS are lacking.MethodsSARC021 randomized patients to receive first-line doxorubicin or doxorubicin plus evofosfamide. The main aim of this study was to compare the outcome and safety of first-line anthracycline-based therapy in older patients compared with those <65 years. IRB approval was obtained at all participating sites and this research meets requirements for protection of human subjects.ResultsOf 640 patients, 209 (33%) were older, with a median age 70 (range 65–89) years. The median overall survival (OS) was 16.7 months (95%CI: 13.2–20.0) in older patients compared to 20.1 months (95%CI: 16.9–23.2) in those aged <65 years (n = 431), HR 1.21 (95%CI: 0.99–1.48), p = .057. The median progression-free survival (PFS) in older patients was 6.3 months (95%CI: 5.8–7.2) compared to 6.0 (95%CI: 5.1–6.4) in those <65 years, HR 0.86 (95%CI: 0.70–1.05), p = .14. Older patients had significantly more hematological (141 [67%] versus 208 [48%], p < .0001), non-hematological (131 [63%] versus 215 [50%], p = .0097) and ≥ Grade 3 adverse events (178 [85%] versus 299 [69%], p = .0002), compared to younger patients. More older patients (30, 14%) stopped treatment due to adverse events compared to younger patients (22, 5%), p = .0001.ConclusionsThe efficacy of first-line anthracycline-based chemotherapy did not differ significantly between older and younger advanced sarcoma patients. Significantly more older patients stopped chemotherapy due to adverse events. These results provide a benchmark for daily clinical practice and future trials in older patients.     

Prediction of treatment-related toxicity and outcome with geriatric assessment in elderly patients with solid malignancies treated with chemotherapy: a systematic review

IntroductionThe number of older patients with cancer is increasing. Standard clinical evaluation of these patients may not be sufficient to determine individual treatment strategies and therefore Geriatric Assessment (GA) may be of clinical value. In this review, we summarize current literature that is available on GA in elderly patients with solid malignancies who receive chemotherapy. We focus on prediction of treatment toxicity, mortality and the role of GA in the decision-making process.DesignWe conducted a systematic search in PubMed. Studied populations needed to fulfill the following criteria: 65 years or older, diagnosis of solid malignancy, treatment with chemotherapy, submission to GA, either designed to study prediction of treatment toxicity or mortality or to evaluate the role of GA in the decision-making process.ResultsOur search provided 411 publications. Thirteen met the predefined criteria. These studies revealed: (i) up to 64% of elderly patients suffer from severe toxicity caused by polychemotherapy, (ii) Nutritional status, functionality and comorbidity are often associated with worse outcome, (iii) GA reveals (unknown) geriatric problems in more than 50% of elderly patients with cancer and (iv) 21%–53% of chemotherapy regimens are being modified based on GA.ConclusionsIn geriatric oncology, an accurate predictive test to guide anticancer treatment in order to prevent serious toxicity is needed. The value of GA in predicting toxicity and mortality in older patients with cancer undergoing treatment with chemotherapy has not been proven. It may be valuable in revealing geriatric problems but current evidence for its usefulness to guide treatment decisions in this setting is limited. However, we are convinced that GAs should be carried out to optimize treatment strategies in elderly patients with cancer to improve treatment efficacy and minimize toxicity.     

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial

BackgroundOlder patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome.MethodsWe performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates.ResultsThirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm.ConclusionsClinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.     

Physical exercise program to older frail patients receiving chemotherapy for colorectal cancer - feasibility and experiences from the GERICO study

IntroductionOlder and frail patients with cancer are at high risk of physical and functional decline during chemotherapy. Exercise interventions can often counteract chemotherapy related toxicity and may help patients to improve or retain physical function and quality of life. Studies evaluating feasibility and the effect of exercise in older patients are lacking. The aim of this study was to investigate the feasibility and effect of an exercise intervention in older frail patients during chemotherapy for colorectal cancer (CRC).Materials and MethodsThis is a secondary analysis from the GERICO study investigating the effect of geriatric interventions in frail patients ≥70 years receiving chemotherapy for CRC. All patients in the present analysis were patients randomized to geriatric interventions and who were found physically frail (low handgrip strength or slow 10 m gait speed) and therefore offered referral to the exercise program for twelve weeks. We evaluated reasons for dropping out and feasibility of an individually tailored exercise program twice a week for twelve weeks. Each 60 min session comprised warm-up followed by progressive resistance training and cool-down followed by an oral protein supplement. Baseline characteristics and the effect of exercise for patients with high and low adherence (attendance of <50% of exercise sessions) were compared.ResultsOf 71 patients in the intervention group, 47 (66%) were found physically frail and were offered referral to the exercise program. Seven patients were referred to municipal physiotherapy before study start. In the remaining population (N = 40) 19 had exercise adherence >50% and 21 had no or low exercise adherence. Baseline characteristics were similar between patients with high and low/no adherence, except for sex (68% and 33% were men in high and low/ no adherence group, respectively). Patients with >50% attendance had significant improvements in physical tests after twelve weeks of exercise.DiscussionLow adherence to the exercise program was seen due to lack of energy and/or treatment related adverse events. Patients with high adherence benefitted from exercise during chemotherapy but did not differ from patients with low adherence at baseline. Consequently, exercise should be offered to all older frail patients receiving chemotherapy for CRC.     

Is age ≥ 70 years an important predictor of adverse events among patients enrolled in metastatic melanoma trials? Findings from pooled analyses of therapeutic trials

BackgroundThe current study was undertaken to explore whether older age predicts adverse event rates in metastatic melanoma patients participating in cancer clinical trials.MethodsSix phase II studies conducted at our institution for patients with metastatic disease were used in these pooled analyses: 1) ABT-510; 2) bortezomib, paclitaxel, and carboplatin; 3) everolimus; 4) bevacizumab, paclitaxel, carboplatin; 5) carboplatin and nab-paclitaxel; and 6) temozolomide and everolimus. In total, 233 patients, 64 elderly (≥ 70 years) and 169 younger, were analyzed for age-based differences in grade 2 or worse adverse events and other clinical outcomes.ResultsDespite the fact that older patients had slightly worse performance scores, no differences in rates of adverse events were observed based on age. Only worse baseline performance score predicted a higher rate of adverse events: patients with performance scores of one or worse were almost 4 times more likely to experience adverse events. Median cancer progression free survival and overall survival were comparable between older and younger patients.ConclusionThese findings suggest that concern for adverse event rates should not preclude the enrollment of elderly melanoma patients to cancer clinical trials. Such patients should continue to be monitored carefully for tumor response and toxicity.     

The influence of clinical assessment (including age) and geriatric assessment on treatment decisions in older patients with cancer

ObjectivesThe aim of this prospective study in older patients with cancer was to evaluate how clinical assessment (including age) determines the physician's treatment decisions, and how geriatric assessment (GA) further influences these decisions.Patients and MethodsPatients aged ≥ 70 years old with cancer were included if a new therapy was considered. All patients underwent a GA and results were communicated to the treating physician. After the final treatment decision, a predefined questionnaire was completed by the physician.ResultsIn total, 937 patients with median age of 76 years old were included. A total of 902 (96.3%) questionnaires were completed by the treating physicians. In 381/902 patients (42.2%) clinical assessment led to a different treatment decision compared to younger patients without co-morbidities. This difference was most prominent for chemotherapy/targeted therapy decisions. In 505/902 cases (56%) the treating physician consulted GA results before the final treatment decision. In these patients, the treatment decision was influenced by clinical assessment in 44.2%. In 31/505 patients (6.1%) the GA further influenced treatment, mostly concerning chemotherapy/targeted therapy. In eight patients GA influenced the physician to choose a more aggressive chemotherapy.ConclusionsPhysicians use different treatment regimens in older versus younger patients, based on clinical assessment, including age. GA results further influence treatment decisions in a minority of patients and may trigger the use of less aggressive as well as more aggressive treatments. GA information is not always utilized by oncologists, indicating the need for better education and sensitization.     

Risk Factors for Hospitalizations Among Older Adults with Gastrointestinal Cancers

BackgroundOlder adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity–related hospitalization among older adults with GI cancers.Patients and MethodsWe performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined.ResultsThis analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized.ConclusionCardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.